Testosterone deficiency, metabolic syndrome and diabetes mellitus

array:24 ["pii" => "S2387020616301395" "issn" => "23870206" "doi" => "10.1016/j.medcle.2015.06.002" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3368" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2015" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2016;146:69-73" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775315004480" "issn" => "00257753" "doi" => "10.1016/j.medcli.2015.06.020" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3368" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2016;146:69-73" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 54 "formatos" => array:2 [ "HTML" => 19 "PDF" => 35 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "Revisión" "titulo" => "Déficit de testosterona, síndrome metabólico y diabetes mellitus" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "69" "paginaFinal" => "73" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Testosterone deficiency, metabolic syndrome and diabetes mellitus" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mercè Fernández-Miró, Juan J. Chillarón, Juan Pedro-Botet" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Mercè" "apellidos" => "Fernández-Miró" ] 1 => array:2 [ "nombre" => "Juan J." "apellidos" => "Chillarón" ] 2 => array:2 [ "nombre" => "Juan" "apellidos" => "Pedro-Botet" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020616301395" "doi" => "10.1016/j.medcle.2015.06.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301395?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315004480?idApp=UINPBA00004N" "url" => "/00257753/0000014600000002/v1_201601130113/S0025775315004480/v1_201601130113/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020616301309" "issn" => "23870206" "doi" => "10.1016/j.medcle.2014.12.003" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3236" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2016;146:74-80" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Central nervous system relapse in diffuse large B cell lymphoma: Risk factors" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "74" "paginaFinal" => "80" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recaída en el sistema nervioso central en el linfoma B difuso de célula grande: factores de riesgo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan-Manuel Sancho, Josep-Maria Ribera" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Juan-Manuel" "apellidos" => "Sancho" ] 1 => array:2 [ "nombre" => "Josep-Maria" "apellidos" => "Ribera" ] 2 => array:1 [ "colaborador" => "on behalf of the Working Group on Diagnosis, Prevention and Treatment of CNS infiltration in patients with DLBCL" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315000755" "doi" => "10.1016/j.medcli.2014.12.025" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315000755?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301309?idApp=UINPBA00004N" "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301309/v1_201605240650/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020616301371" "issn" => "23870206" "doi" => "10.1016/j.medcle.2015.05.049" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3330" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2016;146:67-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Editorial article" "titulo" => "Hyperuricemia and gout: The impact of ultrasonography" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "67" "paginaFinal" => "68" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiperuricemia y gota: impacto de la ecografía" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan García Puig, Eugenio de Miguel" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Juan" "apellidos" => "García Puig" ] 1 => array:2 [ "nombre" => "Eugenio" "apellidos" => "de Miguel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315003024" "doi" => "10.1016/j.medcli.2015.05.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315003024?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301371?idApp=UINPBA00004N" "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301371/v1_201605240650/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Testosterone deficiency, metabolic syndrome and diabetes mellitus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "69" "paginaFinal" => "73" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mercè Fernández-Miró, Juan J. Chillarón, Juan Pedro-Botet" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Mercè" "apellidos" => "Fernández-Miró" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "Juan J." "apellidos" => "Chillarón" "email" => array:1 [ 0 => "Jchillaron@parcdesalutmar.cat" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Juan" "apellidos" => "Pedro-Botet" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Medina Interna-Endocrinología y Nutrición, Centre d’Atenció Integral Dos de Maig, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Instituto Hospital del Mar de Investigaciones Médicas (IMIM), Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Déficit de testosterona, síndrome metabólico y diabetes mellitus" ] ] "textoCompleto" => "IntroductionMale hypogonadism is defined as the reduction of one or two major testicular functions: spermatogenesis and testosterone production. The etiology of these malfunctions is a primary testicular disease (primary hypogonadism) or disease emerging in the hypothalamus/hypophysis (secondary hypogonadism or hypogonadotropic). The consensus of the International Society of Andrology, the International Society for the Study of the Aging, the European Association of Urology, the European Academy of Andrology and the American Society of Andrology recognizes the diagnosis of hypogonadism in men with the recurrent presence of total testosterone levels below 8nmol/l (2.3ng/ml). When the total testosterone levels range from 8 to 12nmol/l (2.3 and 5.21ng/ml) quantification of free testosterone is useful. Thus, levels of free testosterone below 225pmol/l (65pg/ml) are considered diagnostic and support replacement therapy indication.<a class="elsevierStyleCrossRef" href="#bib0205">1</a> The presence of symptoms of hypogonadism, such as dysthymia, decreased libido, muscle mass and hair is needed to establish the diagnosis.Testosterone circulates in plasma bound to: albumin, to the sex hormone-binding globulin (SHBG) and free. Therefore, its overall concentration includes these three forms and is subject to variations in albumin levels and SHBG, being an uncertain index of bioavailable testosterone. The optimal method for quantification of free testosterone is a difficult procedure and not available in most clinical laboratories. Thus, the most accepted method of estimating free testosterone is by Vermeulen formula<a class="elsevierStyleCrossRef" href="#bib0210">2</a> including SHBG, albumin and total testosterone levels, with excellent correlation with the direct determination.Hypogonadism in the general populationIn the general population the prevalence of hypogonadism is from 5 to 12.3% in men aged from 30 to 79, with an incidence of 12.3 per 1000 inhabitants/year.<a class="elsevierStyleCrossRefs" href="#bib0215">3,4</a> Testosterone levels change with age, decreasing by 3.5nmol/l (1ng/ml) from age 20 to 80.<a class="elsevierStyleCrossRef" href="#bib0225">5</a> In the European Male Aging Study, which included 3220 men aged 40–79, total testosterone levels decreased by 0.4% annually and free testosterone by 1.3%.<a class="elsevierStyleCrossRef" href="#bib0230">6</a>We should distinguish the common hypogonadism from late onset caused by a functional suppression of the hypothalamic–pituitary–testicular axis due to age-related comorbidities, especially obesity. The late-onset hypogonadism has been associated with increased all-cause mortality by up to 5 times.<a class="elsevierStyleCrossRef" href="#bib0235">7</a>Pathophysiology of hypogonadism in diabetesSeveral studies have found an inverse relationship between the testosterone levels, insulin resistance and obesity. This relationship can be explained by several hypotheses. First, testosterone is metabolized to 17-beta-estradiol by aromatase located in adipocytes. Due to excess aromatization lower testosterone levels allow increased lipoprotein lipase activity, resulting in increased uptake of fatty acids and triglycerides in the adipocytes. Consequently, there is increased fatty mass which is correlated with higher insulin resistance and lower testosterone levels.<a class="elsevierStyleCrossRef" href="#bib0240">8</a> The second hypothesis suggests that the 17-beta-estradiol and adipokines, interleukin-6, tumor necrosis factor alpha and leptin inhibit the response of the hypothalamic–pituitary–testicular axis in response to lower testosterone levels. This impaired homeostatic response explains why some obese men have a hypogonadotropic hypogonadism with normal or low levels of gonadotropins in the presence of low testosterone levels. Furthermore, the insulin resistance is associated with lower testosterone secretion by Leydig cells.<a class="elsevierStyleCrossRef" href="#bib0245">9</a> Moreover, in vitro studies that have evaluated the direct effect of testosterone in adipocytes show that androgen treatment decreases adipogenesis and increases lipolysis by increasing the number of beta adrenergic receptors.<a class="elsevierStyleCrossRefs" href="#bib0250">10,11</a>Prevalence of hypogonadism in diabetesPatients with type 2 diabetes mellitus (DM2) have shown prevalence of frank hypogonadism (total testosterone levels below 8nmol/l) from 4.4% to 17.7% and extreme hypogonadism (total testosterone ranging from 8 to 12nmol/l) from 25% to 32.1%.<a class="elsevierStyleCrossRefs" href="#bib0260">12,13</a> In type 1 diabetes mellitus (DM1) it has been reported that around 7.2% of patients have total testosterone levels below 2.8ng/ml (<10nmol/l), similar to the general population.<a class="elsevierStyleCrossRef" href="#bib0270">14</a> However, up to 20% of patients with DM1 have free testosterone levels below 225pmol/l (65pg/ml), higher levels than those described in healthy men and lower than in patients with DM2. Age is the major predictor of low levels of free testosterone. Therefore, for each decade of life the prevalence of this condition is multiplied by two.<a class="elsevierStyleCrossRef" href="#bib0275">15</a>Hypogonadotropic hypogonadism and metabolic syndromeThere is a number of factors in different population groups that can lead to androgen deficiency, increasing the prevalence of hypogonadism. These include the characteristic features of the metabolic syndrome such as obesity, hyperglycemia, hypertension and atherogenic dyslipidemia. A large number of epidemiological studies have related testosterone with metabolic syndrome, and its components, individually, have been associated with lower testosterone levels. A Finnish study with 1896 non-diabetic males found lower total and free testosterone figures in those who had metabolic syndrome. Men with free testosterone levels in the lowest tertile showed an increased risk of metabolic syndrome by 2.7 (95% CI: 2.0–3.7) and 1.7 times (95% CI:1.2–2.4) after age and body mass index (BMI) adjustment, respectively.<a class="elsevierStyleCrossRef" href="#bib0280">16</a> Conversely, negative associations have been proved between testosterone levels and risk of metabolic syndrome or insulin resistance.<a class="elsevierStyleCrossRef" href="#bib0285">17</a>Hypogonadotropic hypogonadism and insulin resistanceDifferent evidences in healthy men have reported an inverse correlation between total testosterone and insulin, blood sugar and BMI.<a class="elsevierStyleCrossRefs" href="#bib0245">9,12,18,19</a> Lower testosterone levels have also been reported in first-degree male relatives of patients with diabetes compared to healthy controls, in relation to increased insulin resistance, which in turn means higher risk of developing diabetes.<a class="elsevierStyleCrossRef" href="#bib0300">20</a>The inverse correlation between total testosterone and insulin is determined by SHBG levels, which are also lower in patients with insulin resistance. Insulin is a key regulator factor on the hepatic production of SHBG. Additionally, it has been reported that men with decreased SHBG levels are at higher risk of developing metabolic syndrome.<a class="elsevierStyleCrossRef" href="#bib0305">21</a>In vitro studies have shown that insulin at physiological levels is a powerful inhibitor of SHBG production. This relationship between testosterone and insulin resistance found in healthy individuals has also been confirmed in those with diabetes. There is a significant association between HOMA-IR index with low levels of total testosterone after age and BMI adjustment. Insulin sensitivity was also associated with free testosterone levels, so that individuals with DM2 and lower levels of free testosterone had higher insulin resistance after age and BMI adjustment.<a class="elsevierStyleCrossRef" href="#bib0275">15</a>Patients with DM1 are not exempt from presenting metabolic syndrome or insulin resistance. In Europe, several studies show a 30–40% prevalence of metabolic syndrome in patients with DM1.<a class="elsevierStyleCrossRefs" href="#bib0310">22–24</a> Furthermore, the relationship between insulin resistance in patients with DM1 and chronic complications of diabetes, especially microangiopathy,<a class="elsevierStyleCrossRefs" href="#bib0310">22,23,25</a> has been widely described. Consistent with these results and those obtained in patients with DM2, a direct association has been proved between free and overall testosterone levels and insulin sensitivity in this group of patients.<a class="elsevierStyleCrossRefs" href="#bib0270">14,15</a>Hypogonadotropic hypogonadism and dyslipidemiaIn several studies a positive correlation has been reported between levels of total and free testosterone with HDL cholesterol and ApoA1 (r=0.12; p<0.01),<a class="elsevierStyleCrossRef" href="#bib0330">26</a> as well as a negative correlation with total cholesterol, LDL and triglycerides.<a class="elsevierStyleCrossRef" href="#bib0335">27</a> The Massachusetts Male Aging Study, conducted with 1661 men aged from 40 to 70 showed that the relationship between HDL cholesterol and total and free testosterone was most evident in those with cardiovascular disease, where increased 5nmol/l was associated with an increased HDL cholesterol by 6%.<a class="elsevierStyleCrossRef" href="#bib0340">28</a>It has also been observed an inverse association between testosterone levels and carotid intima-media thickness in males in cross-sectional studies; in the logistic regression model, after adjustment for cardiovascular risk factors, males with testosterone levels in the lowest quintile (<9nmol/l) reported a higher risk of being in the top quintile of carotid intima-media thickness.<a class="elsevierStyleCrossRef" href="#bib0345">29</a>Finally, longitudinal studies have found an inverse relationship both in total and bioavailable testosterone levels with the progression of aortic atherosclerosis. The Rotterdam study evaluated in 1032 nonsmoker men emergence of aortic atherosclerosis by detecting calcium in the abdominal aorta. It was found that men with levels of total and bioavailable testosterone in the highest tertile had a lower prevalence of severe aortic atherosclerosis (RR: 0.4 [95% CI 0.2–0.9]), and also a lower incidence after 6.5 years of follow-up.<a class="elsevierStyleCrossRef" href="#bib0350">30</a>Hypogonadotropic hypogonadism and hypertensionContrary to what was observed with testosterone levels, blood pressure in men increases with age. In this regard, low testosterone levels have been linked with elevated systolic and diastolic blood pressure, and low testosterone levels have been reported in hypertensive individuals. In the Tromsø study, levels of total testosterone and SHBG were associated inversely with systolic blood pressure. Men with systolic blood pressure over 140mm Hg or diastolic pressure over 90mmHg had lower levels of total and free testosterone and SHBG after adjustment for BMI. The levels of total testosterone and SHBG were also associated inversely with left ventricular mass.<a class="elsevierStyleCrossRef" href="#bib0355">31</a>Testosterone replacement therapy in patients with hypogonadism and diabetesSeveral studies have confirmed the beneficial effects of testosterone therapy on insulin sensitivity and obesity markers. Androgen treatment reduces adipogenesis and increases lipolysis.<a class="elsevierStyleCrossRef" href="#bib0250">10</a> There have been favorable anthropometric changes after testosterone replacement therapy, such as a mean 15kg weight reduction, 4.7kg/m2 BMI reduction, 10cm reduction in abdominal girth and up to 5.6% fatty mass lost<a class="elsevierStyleCrossRefs" href="#bib0360">32–36</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>As for changes in glucose metabolism after testosterone replacement therapy there has been reduced glycated hemoglobin, fasting glucose, fasting insulin and HOMA-IR index<a class="elsevierStyleCrossRefs" href="#bib0365">33–38</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The first randomized, placebo-controlled and crossover clinical trial by Kapoor et al. in 24 patients with DM2 and hypogonadism showed that parenteral administration of testosterone for 3 months produced a significant decreased HOMA-IR index in patients not receiving insulin and lower insulin requirements in patients who were treated with insulin. They also showed significant decreased fasting glucose, glycosylated hemoglobin and fasting insulinemia.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> These findings were replicated in another randomized, placebo-controlled clinical trial in 32 patients with DM2 and hypogonadism treated with transdermal testosterone for 52 weeks,<a class="elsevierStyleCrossRef" href="#bib0375">35</a> and confirmed in the Testosterone Replacement In hypogonadal men with Metabolic Syndrome and/or Type 2 Diabetes clinical trial, with 220 patients participating with hypogonadism and DM2 and/or metabolic syndrome according to the criteria of the International Diabetes Federation. HOMA-IR index was significantly decreased in the group treated with testosterone by 15.2% and 16.4% at 6 and 12 months, respectively, compared with placebo, as well as decreased glycated hemoglobin by 0.4% was observed at 9 months in diabetic patients on hormonal therapy.<a class="elsevierStyleCrossRef" href="#bib0385">37</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>On lipid profile, testosterone replacement therapy has also obtained reduction in total cholesterol, LDL cholesterol, triglycerides and total cholesterol/HDL ratio as well as higher HDL cholesterol<a class="elsevierStyleCrossRefs" href="#bib0370">34,35,37–39</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>In studies with smaller sample size the testosterone replacement therapy has shown changes in other markers of cardiovascular risk, such as a significant decrease in carotid intima-media thickness,<a class="elsevierStyleCrossRef" href="#bib0400">40</a> the number of episodes of angina,<a class="elsevierStyleCrossRef" href="#bib0390">38</a> systolic and diastolic blood pressure, and C-reactive protein (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>ConclusionsOne out of 3 patients with type 2 diabetes and/or metabolic syndrome have frank or extreme hypogonadotropic hypogonadism. Because of the increased sedentary lifestyle and obesity, patients with DM1 with a similar type 2 diabetes phenotype, who generally meet diagnostic criteria for metabolic syndrome are becoming more and more frequent. Therefore, patients with DM1 and any component of the metabolic syndrome might also have hypogonadotropic hypogonadism. In this regard, prevalence of decreased levels of free testosterone in individuals with DM1 has been reported as up to 20%. In these patients it is important to establish an early diagnosis of hypogonadism because testosterone replacement therapy has caused, in patients with type 2 diabetes and/or metabolic syndrome, improved cardiometabolic profile, resulting from increased sensitivity to insulin. Currently, no studies are available evaluating the effect of testosterone replacement therapy in individuals with DM1 and hypogonadotropic hypogonadism.Conflict of interestsThe authors report no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres644390" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec657458" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres644389" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec657459" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Hypogonadism in the general population" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Pathophysiology of hypogonadism in diabetes" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Prevalence of hypogonadism in diabetes" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Hypogonadotropic hypogonadism and metabolic syndrome" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Hypogonadotropic hypogonadism and insulin resistance" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Hypogonadotropic hypogonadism and dyslipidemia" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Hypogonadotropic hypogonadism and hypertension" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Testosterone replacement therapy in patients with hypogonadism and diabetes" ] 13 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions" ] 14 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interests" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-04-14" "fechaAceptado" => "2015-06-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec657458" "palabras" => array:3 [ 0 => "Hypogonadism" 1 => "Testosterone deficiency" 2 => "Hypogonadism and diabetes" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec657459" "palabras" => array:3 [ 0 => "Hipogonadismo" 1 => "Déficit de testosterona" 2 => "Hipogonadismo y diabetes" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El déficit de testosterona en la edad adulta se relaciona con depresión, disminución de la libido, energía, hematocrito, masa muscular y de la densidad mineral ósea. En los últimos años, también se ha asociado con diversos componentes del síndrome metabólico, que a su vez se relacionan con un aumento de hasta 5 veces en el riesgo de enfermedad cardiovascular. Así, las concentraciones bajas de testosterona se asocian con una mayor resistencia a la insulina, incremento de la masa grasa, colesterol HDL bajo, triglicéridos elevados e hipertensión arterial. Inversamente, el tratamiento sustitutivo en pacientes con déficit de testosterona y diabetes mellitus tipo 2 y/o síndrome metabólico ha demostrado reducciones en la resistencia a la insulina, colesterol total, LDL y triglicéridos, y una mejoría del control glucémico y los parámetros antropométricos." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Fernández-Miró M, Chillarón JJ, Pedro-Botet J. Déficit de testosterona, síndrome metabólico y diabetes mellitus. Med Clin (Barc). 2016;146:69–73." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.1kg in 5 years −15.35kg in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yassin et Doros<a class="elsevierStyleCrossRef" href="#bib0360">32</a> Saad et al.<a class="elsevierStyleCrossRef" href="#bib0365">33</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−4.77kg/m2 in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Saad et al.<a class="elsevierStyleCrossRef" href="#bib0365">33</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abdominal girth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.63cm in 3 months −10cm in 12 months −8.5cm in 5 years −9.4cm in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kapoor et al.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> Heufelder et al.<a class="elsevierStyleCrossRef" href="#bib0375">35</a> Saad et al.<a class="elsevierStyleCrossRef" href="#bib0365">33</a> Yassin et Doros<a class="elsevierStyleCrossRef" href="#bib0365">33</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Waist/hip ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.96% in 3 months −0.03 in 3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Boyanov et al.<a class="elsevierStyleCrossRef" href="#bib0380">36</a> Kapoor et al.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fatty mass \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−5.65% in 3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Boyanov et al.<a class="elsevierStyleCrossRef" href="#bib0380">36</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1062187.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Anthropometric changes after testosterone replacement therapy in patients with hypogonadism." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glycosylated hemoglobin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.8% in 3 months −0.37% in 3 months −0.8% in 12 months −0.44% in 12 months −2.48% in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Boyanov et al.<a class="elsevierStyleCrossRef" href="#bib0380">36</a> Kapoor et al.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> Heufelder et al.<a class="elsevierStyleCrossRef" href="#bib0375">35</a> Jones et al.<a class="elsevierStyleCrossRef" href="#bib0385">37</a> Saad et al.<a class="elsevierStyleCrossRef" href="#bib0365">33</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fasting glucose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.58mmol/l in 3 months −1.2mmol/l in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kapoor et al.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> Saad et al.<a class="elsevierStyleCrossRef" href="#bib0365">33</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fasting insulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−40.2pmol/l in 12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Heufelder et al.<a class="elsevierStyleCrossRef" href="#bib0375">35</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HOMA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.73 in 3 months −0.9 in 12 months −16.4% in 12 months −0.6 in 3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kapoor et al.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> Heufelder et al.<a class="elsevierStyleCrossRef" href="#bib0375">35</a> Jones et al.<a class="elsevierStyleCrossRef" href="#bib0385">37</a> Cornoldi et al.<a class="elsevierStyleCrossRef" href="#bib0390">38</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1062188.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Changes in glucose metabolism after testosterone replacement therapy in hypogonadal patients." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HDL, high-density lipoprotein; LDL, low-density lipoprotein." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total cholesterol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.4mmol/l in 3 months −0.28mmol/l in 12 months −2.4mmol/l in 5 years −0.44mmol/l in 3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kapoor et al.<a class="elsevierStyleCrossRef" href="#bib0370">34</a> Jones et al.<a class="elsevierStyleCrossRef" href="#bib0385">37</a> Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> Cornoldi et al.<a class="elsevierStyleCrossRef" href="#bib0390">38</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDL cholesterol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.16mmol/l in 12 months −1.4mmol/l in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Jones et al.<a class="elsevierStyleCrossRef" href="#bib0385">37</a> Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL cholesterol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+0.2mmol/l in 12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Heufelder et al.<a class="elsevierStyleCrossRef" href="#bib0375">35</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglycerides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.7mmol/l in 12 months −0.36mmol/l −0.9mmol/l in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Heufelder et al.<a class="elsevierStyleCrossRef" href="#bib0375">35</a> Cornoldi et al.<a class="elsevierStyleCrossRef" href="#bib0390">38</a> Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total choleesterol/HDL ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.95 in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1062189.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Changes in lipid profile after testosterone replacement therapy in patients with hypogonadism." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Carotid intima-media thickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduction. −0.22mm at 12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Aversa et al.<a class="elsevierStyleCrossRef" href="#bib0400">40</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of angina episodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduction by 34% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cornoldi et al.<a class="elsevierStyleCrossRef" href="#bib0390">38</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C-reactive protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−5.26U/l in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−15mmHg in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diastolic blood pressure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.9mmHg in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aspartate aminotransferase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−22U/l in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alanine aminotransferase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−23.34U/l in 5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Traish et al.<a class="elsevierStyleCrossRef" href="#bib0395">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1062190.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Changes in other markers of cardiovascular risk after testosterone replacement therapy in patients with hypogonadism." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0205" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Wang" 1 => "E. Nieschlag" 2 => "R. Swerdloff" 3 => "H.M. Behre" 4 => "W.J. Hellstrom" 5 => "L.J. Gooren" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2164/jandrol.108.006486" "Revista" => array:6 [ "tituloSerie" => "J Androl" "fecha" => "2009" "volumen" => "30" "paginaInicial" => "1" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18772485" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0210" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A critical evaluation of simple methods for the estimation of free testosterone in serum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Vermeulen" 1 => "L. Verdonck" 2 => "J.M. Kaufman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem.84.10.6079" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "1999" "volumen" => "84" "paginaInicial" => "3666" "paginaFinal" => "3672" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10523012" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0215" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.B. Araujo" 1 => "A.B. O’Donnell" 2 => "D.J. Brambilla" 3 => "W.B. Simpson" 4 => "C. Longcope" 5 => "A.M. Matsumoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2003-031719" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2004" "volumen" => "89" "paginaInicial" => "5920" "paginaFinal" => "5926" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15579737" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0220" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of symptomatic androgen deficiency in men" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.B. Araujo" 1 => "G.R. Esche" 2 => "V. Kupelian" 3 => "A.B. O¿Donnell" 4 => "T.G. Travison" 5 => "R.E. Williams" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2007-1245" "Revista" => array:7 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2007" "volumen" => "92" "paginaInicial" => "4241" "paginaFinal" => "4247" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17698901" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0021915014013513" "estado" => "S300" "issn" => "00219150" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0225" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age differences in serum androgen levels in normal adult males" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.E. Purifoy" 1 => "L.H. Koopmans" 2 => "D.M. Mayes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Biol" "fecha" => "1981" "volumen" => "53" "paginaInicial" => "499" "paginaFinal" => "511" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7199020" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0230" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypothalamic–pituitary–testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.C. Wu" 1 => "A. Tajar" 2 => "S.R. Pye" 3 => "A.J. Silman" 4 => "J.D. Finn" 5 => "T.W. O’Neill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2007-1972" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2008" "volumen" => "93" "paginaInicial" => "2737" "paginaFinal" => "2745" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18270261" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0235" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Late-onset hypogonadism and mortality in aging men" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.R. Pye" 1 => "I.T. Huhtaniemi" 2 => "J.D. Finn" 3 => "D.M. Lee" 4 => "T.W. O’Neill" 5 => "A. Tajar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2013-2052" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2014" "volumen" => "99" "paginaInicial" => "1357" "paginaFinal" => "1366" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24423283" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0240" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt—a major factor in the genesis of morbid obesity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.G. Cohen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1054/mehy.1997.0624" "Revista" => array:6 [ "tituloSerie" => "Med Hypotheses" "fecha" => "1999" "volumen" => "52" "paginaInicial" => "49" "paginaFinal" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10342671" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0245" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Pitteloud" 1 => "M. Hardin" 2 => "A.A. Dwyer" 3 => "E. Valassi" 4 => "M. Yialama" 5 => "D. Elahi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2004-2190" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2005" "volumen" => "90" "paginaInicial" => "2636" "paginaFinal" => "2641" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15713702" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0250" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The adipose tissue metabolism: role of testosterone and dehydroepiandrosterone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G. De Pergola" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Obes Relat Metab Disord" "fecha" => "2000" "volumen" => "24" "paginaInicial" => "S59" "paginaFinal" => "S63" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10997611" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0255" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Androgens and body fat distribution" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Blouin" 1 => "A. Boivin" 2 => "A. Tchernof" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jsbmb.2007.09.001" "Revista" => array:6 [ "tituloSerie" => "J Steroid Biochem Mol Biol" "fecha" => "2008" "volumen" => "108" "paginaInicial" => "272" "paginaFinal" => "280" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17945484" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0260" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.G. Anderson" 1 => "A. Heald" 2 => "N. Younger" 3 => "S. Bujawansa" 4 => "R.P. Narayanan" 5 => "A. McCulloch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pcd.2011.07.006" "Revista" => array:7 [ "tituloSerie" => "Prim Care Diabetes" "fecha" => "2012" "volumen" => "6" "paginaInicial" => "143" "paginaFinal" => "148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21982717" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673611607848" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0265" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D. Kappor" 1 => "H. Aldred" 2 => "S. Clark" 3 => "K.S. Channer" 4 => "T.H. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc06-1426" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2007" "volumen" => "30" "paginaInicial" => "911" "paginaFinal" => "917" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17392552" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0270" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age, insulin requirements, waist circumference and triglycerides predict hypogonadotropic hypogonadism in patients with type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Chillarón" 1 => "M. Fernández-Miró" 2 => "M. Albareda" 3 => "L. Vila" 4 => "C. Colom" 5 => "S. Fontserè" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jsm.12748" "Revista" => array:6 [ "tituloSerie" => "J Sex Med" "fecha" => "2015" "volumen" => "12" "paginaInicial" => "76" "paginaFinal" => "82" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25394376" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0275" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low testosterone levels are common and associated with insulin resistance in men with diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Grossmann" 1 => "M.C. Thomas" 2 => "S. Panagiotopoulos" 3 => "K. Sharpe" 4 => "R.J. Macisaac" 5 => "S. Clarke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2007-2177" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2008" "volumen" => "93" "paginaInicial" => "1834" "paginaFinal" => "1840" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18319314" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0280" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sex hormones, inflammation and the metabolic syndrome: a population-based study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.E. Laaksonen" 1 => "L. Niskanen" 2 => "K. Punnonen" 3 => "K. Nyyssönen" 4 => "T.P. Tuomainen" 5 => "R. Salonen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2003" "volumen" => "149" "paginaInicial" => "601" "paginaFinal" => "608" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14641004" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0285" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contribution of age and declining androgen levels to features of the metabolic syndrome in men" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Blouin" 1 => "J.P. Després" 2 => "C. Couillard" 3 => "A. Tremblay" 4 => "D. Prud’homme" 5 => "C. Bouchard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.metabol.2005.03.006" "Revista" => array:6 [ "tituloSerie" => "Metabolism" "fecha" => "2005" "volumen" => "54" "paginaInicial" => "1034" "paginaFinal" => "1040" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16092053" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0290" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Can clinical factors estimate insulin resistance in type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.V. Williams" 1 => "J.R. Erbey" 2 => "D. Becker" 3 => "S. Arslanian" 4 => "T.J. Orchard" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Diabetes" "fecha" => "2000" "volumen" => "49" "paginaInicial" => "626" "paginaFinal" => "632" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10871201" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S073510971302086X" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0295" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between plasma testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Simon" 1 => "M.A. Charles" 2 => "K. Nahoul" 3 => "G. Orssaud" 4 => "J. Kremski" 5 => "V. Hully" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem.82.2.3766" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "1997" "volumen" => "82" "paginaInicial" => "682" "paginaFinal" => "685" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9024276" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0300" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Androgens, insulin resistance and vascular disease in men" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Kappor" 1 => "C.J. Malkin" 2 => "K.S. Channer" 3 => "T.H. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Endocrinol (Oxf)" "fecha" => "2005" "volumen" => "63" "paginaInicial" => "239" "paginaFinal" => "250" "itemHostRev" => array:3 [ "pii" => "S0735109710002809" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0305" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aging, androgens, and the metabolic syndrome in a longitudinal study of aging" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Rodriguez" 1 => "D.C. Muller" 2 => "E.J. Metter" 3 => "M. Maggio" 4 => "S.M. Harman" 5 => "M.R. Blackman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2006-2764" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2007" "volumen" => "92" "paginaInicial" => "3568" "paginaFinal" => "3572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17595254" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0310" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.M. Thorn" 1 => "C. Forsblom" 2 => "J. Fagerudd" 3 => "M.C. Thomas" 4 => "K. Pettersson-Fernholm" 5 => "M. Saraheimo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2005" "volumen" => "28" "paginaInicial" => "2019" "paginaFinal" => "2024" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16043748" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0315" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "The Metascreen Writing Committee" "etal" => false "autores" => array:5 [ 0 => "R. Bonadonna" 1 => "D. Cucinotta" 2 => "D. Fedele" 3 => "G. Riccardi" 4 => "A. Tiengo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc06-0942" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2006" "volumen" => "29" "paginaInicial" => "2701" "paginaFinal" => "2707" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17130208" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0320" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolic syndrome and type-1 diabetes mellitus: prevalence and associated factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Chillarón" 1 => "J.A. Flores-Le-Roux" 2 => "A. Goday" 3 => "D. Benaiges" 4 => "M.J. Carrera" 5 => "J. Puig" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Cardiol" "fecha" => "2010" "volumen" => "63" "paginaInicial" => "423" "paginaFinal" => "429" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20334808" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0325" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estimated glucose disposal rate in assessment of the metabolic syndrome and microvascular complications in patients with type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Chillarón" 1 => "A. Goday" 2 => "J. Flores-Le-Roux" 3 => "D. Benaiges" 4 => "M.J. Carrera" 5 => "J. Puig" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2009-0960" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2009" "volumen" => "94" "paginaInicial" => "3530" "paginaFinal" => "3534" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19584183" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0330" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I. Van Pottelbergh" 1 => "L. Braeckman" 2 => "D. de Bacquer" 3 => "G. de Backer" 4 => "J.M. Kaufman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "2003" "volumen" => "166" "paginaInicial" => "95" "paginaFinal" => "102" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12482555" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0335" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relationship between endogenous testosterone and lipid profile in middle-aged and elderly Chinese men" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Zhang" 1 => "H. Zhang" 2 => "X. Zhang" 3 => "B. Zhang" 4 => "F. Wang" 5 => "C. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/EJE-13-0802" "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2014" "volumen" => "170" "paginaInicial" => "487" "paginaFinal" => "494" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24394726" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0340" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Higher testosterone levels are associated with increased high-density lipoprotein cholesterol in men with cardiovascular disease: results from the Massachusetts Male Aging Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.T. Page" 1 => "B.A. Mohr" 2 => "C.L. Link" 3 => "A.B. O’Donnell" 4 => "W.J. Bremner" 5 => "J.B. McKinlay" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1745-7262.2008.00332.x" "Revista" => array:7 [ "tituloSerie" => "Asian J Androl" "fecha" => "2008" "volumen" => "10" "paginaInicial" => "193" "paginaFinal" => "200" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18097527" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109703001876" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0345" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low testosterone levels are associated with carotid atherosclerosis in men" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Svartberg" 1 => "D. von Mühlen" 2 => "E. Mathiesen" 3 => "O. Joakimsen" 4 => "K.H. Bønaa" 5 => "E. Stensland-Bugge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2796.2006.01637.x" "Revista" => array:6 [ "tituloSerie" => "J Intern Med" "fecha" => "2006" "volumen" => "259" "paginaInicial" => "576" "paginaFinal" => "582" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16704558" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0350" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: The Rotterdam study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.E. Hak" 1 => "J.C. Witteman" 2 => "F.H. de Jong" 3 => "M.I. Geerlings" 4 => "A. Hofman" 5 => "H.A. Pols" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem.87.8.8762" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2002" "volumen" => "87" "paginaInicial" => "3632" "paginaFinal" => "3639" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12161487" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0355" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Svartberg" 1 => "D. von Mühlen" 2 => "H. Schirmer" 3 => "E. Barrett-Connor" 4 => "J. Sundfjord" 5 => "R. Jorde" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2004" "volumen" => "150" "paginaInicial" => "65" "paginaFinal" => "71" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14713281" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0360" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Testosterone theraphy in hypogonadal men results in sustained and clinically meaningful weight loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Yassin" 1 => "G. Doros" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/cob.12022" "Revista" => array:6 [ "tituloSerie" => "Clin Obes" "fecha" => "2013" "volumen" => "3" "paginaInicial" => "73" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24163704" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0365" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Saad" 1 => "A. Haider" 2 => "G. Doros" 3 => "A. Traish" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Obesity (Silver Spring)" "fecha" => "2013" "volumen" => "21" "paginaInicial" => "1975" "paginaFinal" => "1981" "itemHostRev" => array:3 [ "pii" => "S0002934313009273" "estado" => "S300" "issn" => "00029343" ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0370" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Kapoor" 1 => "E. Goodwin" 2 => "K.S. Channer" 3 => "T.H. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/eje.1.02166" "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2006" "volumen" => "154" "paginaInicial" => "899" "paginaFinal" => "906" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16728551" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0375" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycaemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.E. Heufelder" 1 => "F. Saad" 2 => "M.C. Bunck" 3 => "L. Gooren" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2164/jandrol.108.007005" "Revista" => array:6 [ "tituloSerie" => "J Androl" "fecha" => "2009" "volumen" => "30" "paginaInicial" => "726" "paginaFinal" => "733" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19578132" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0380" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Testosterone supplemetation in men with type 2 diabetes, visceral obesity and partial androgen deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Boyanov" 1 => "Z. Boneva" 2 => "V.G. Christov" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Aging Male" "fecha" => "2003" "volumen" => "6" "paginaInicial" => "1" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12809074" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0385" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.H. Jones" 1 => "S. Arver" 2 => "H.M. Behre" 3 => "J. Buvat" 4 => "E. Meuleman" 5 => "I. Moncada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc10-1233" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2001" "volumen" => "34" "paginaInicial" => "828" "paginaFinal" => "837" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21386088" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0390" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Cornoldi" 1 => "G. Caminiti" 2 => "G. Marazzi" 3 => "C. Vitale" 4 => "R. Patrizi" 5 => "M. Volterrani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2008.12.107" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2010" "volumen" => "142" "paginaInicial" => "50" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19361872" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0395" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.M. Traish" 1 => "A. Haider" 2 => "G. Doros" 3 => "F. Saad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ijcp.12319" "Revista" => array:6 [ "tituloSerie" => "Int J Clin Pract" "fecha" => "2014" "volumen" => "68" "paginaInicial" => "314" "paginaFinal" => "329" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24127736" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0400" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Aversa" 1 => "R. Bruzziches" 2 => "D. Francomano" 3 => "G. Rosano" 4 => "A.M. Isidori" 5 => "A. Lenzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1743-6109.2010.01931.x" "Revista" => array:6 [ "tituloSerie" => "J Sex Med" "fecha" => "2010" "volumen" => "7" "paginaInicial" => "3495" "paginaFinal" => "3503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20646185" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301395/v1_201605240650/en/main.assets" "Apartado" => array:4 [ "identificador" => "43313" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Reviews" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014600000002/v1_201605240650/S2387020616301395/v1_201605240650/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301395?idApp=UINPBA00004N"]

Statistics

Review

Testosterone deficiency, metabolic syndrome and diabetes mellitus

Déficit de testosterona, síndrome metabólico y diabetes mellitus

Mercè Fernández-Miróa,b, Juan J. Chillarónb,c,d,

Corresponding author

Jchillaron@parcdesalutmar.cat

Corresponding author.

, Juan Pedro-Botetb,c,d

a Servicio de Medina Interna-Endocrinología y Nutrición, Centre d’Atenció Integral Dos de Maig, Barcelona, Spain

b Departamento de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain

c Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, Spain

d Instituto Hospital del Mar de Investigaciones Médicas (IMIM), Barcelona, Spain

Read

Times
was read the article

Total PDF

Total HTML

Share statistics

 array:24 [
  "pii" => "S2387020616301395"
  "issn" => "23870206"
  "doi" => "10.1016/j.medcle.2015.06.002"
  "estado" => "S300"
  "fechaPublicacion" => "2016-01-15"
  "aid" => "3368"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;. All rights reserved"
  "copyrightAnyo" => "2015"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Med Clin. 2016;146:69-73"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0025775315004480"
      "issn" => "00257753"
      "doi" => "10.1016/j.medcli.2015.06.020"
      "estado" => "S300"
      "fechaPublicacion" => "2016-01-15"
      "aid" => "3368"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Med Clin. 2016;146:69-73"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 54
        "formatos" => array:2 [
          "HTML" => 19
          "PDF" => 35
        ]
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
        "titulo" => "D&#233;ficit de testosterona&#44; s&#237;ndrome metab&#243;lico y diabetes mellitus"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "69"
            "paginaFinal" => "73"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Testosterone deficiency&#44; metabolic syndrome and diabetes mellitus"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Merc&#232; Fern&#225;ndez-Mir&#243;, Juan J&#46; Chillar&#243;n, Juan Pedro-Botet"
            "autores" => array:3 [
              0 => array:2 [
                "nombre" => "Merc&#232;"
                "apellidos" => "Fern&#225;ndez-Mir&#243;"
              ]
              1 => array:2 [
                "nombre" => "Juan J&#46;"
                "apellidos" => "Chillar&#243;n"
              ]
              2 => array:2 [
                "nombre" => "Juan"
                "apellidos" => "Pedro-Botet"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2387020616301395"
          "doi" => "10.1016/j.medcle.2015.06.002"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301395?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315004480?idApp=UINPBA00004N"
      "url" => "/00257753/0000014600000002/v1_201601130113/S0025775315004480/v1_201601130113/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2387020616301309"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2014.12.003"
    "estado" => "S300"
    "fechaPublicacion" => "2016-01-15"
    "aid" => "3236"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "rev"
    "cita" => "Med Clin. 2016;146:74-80"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Central nervous system relapse in diffuse large B cell lymphoma&#58; Risk factors"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "74"
          "paginaFinal" => "80"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Reca&#237;da en el sistema nervioso central en el linfoma B difuso de c&#233;lula grande&#58; factores de riesgo"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Juan-Manuel Sancho, Josep-Maria Ribera"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Juan-Manuel"
              "apellidos" => "Sancho"
            ]
            1 => array:2 [
              "nombre" => "Josep-Maria"
              "apellidos" => "Ribera"
            ]
            2 => array:1 [
              "colaborador" => "on behalf of the Working Group on Diagnosis&#44; Prevention and Treatment of CNS infiltration in patients with DLBCL"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775315000755"
        "doi" => "10.1016/j.medcli.2014.12.025"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315000755?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301309?idApp=UINPBA00004N"
    "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301309/v1_201605240650/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2387020616301371"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2015.05.049"
    "estado" => "S300"
    "fechaPublicacion" => "2016-01-15"
    "aid" => "3330"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Med Clin. 2016;146:67-8"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>"
      "titulo" => "Hyperuricemia and gout&#58; The impact of ultrasonography"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "67"
          "paginaFinal" => "68"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Hiperuricemia y gota&#58; impacto de la ecograf&#237;a"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Juan Garc&#237;a Puig, Eugenio de Miguel"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "Juan"
              "apellidos" => "Garc&#237;a Puig"
            ]
            1 => array:2 [
              "nombre" => "Eugenio"
              "apellidos" => "de Miguel"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775315003024"
        "doi" => "10.1016/j.medcli.2015.05.009"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315003024?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301371?idApp=UINPBA00004N"
    "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301371/v1_201605240650/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Testosterone deficiency&#44; metabolic syndrome and diabetes mellitus"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "69"
        "paginaFinal" => "73"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Merc&#232; Fern&#225;ndez-Mir&#243;, Juan J&#46; Chillar&#243;n, Juan Pedro-Botet"
        "autores" => array:3 [
          0 => array:3 [
            "nombre" => "Merc&#232;"
            "apellidos" => "Fern&#225;ndez-Mir&#243;"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          1 => array:4 [
            "nombre" => "Juan J&#46;"
            "apellidos" => "Chillar&#243;n"
            "email" => array:1 [
              0 => "Jchillaron&#64;parcdesalutmar&#46;cat"
            ]
            "referencia" => array:4 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Juan"
            "apellidos" => "Pedro-Botet"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Servicio de Medina Interna-Endocrinolog&#237;a y Nutrici&#243;n&#44; Centre d&#8217;Atenci&#243; Integral Dos de Maig&#44; Barcelona&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Medicina&#44; Universitat Aut&#242;noma de Barcelona&#44; Barcelona&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital del Mar&#44; Barcelona&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Instituto Hospital del Mar de Investigaciones M&#233;dicas &#40;IMIM&#41;&#44; Barcelona&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "D&#233;ficit de testosterona&#44; s&#237;ndrome metab&#243;lico y diabetes mellitus"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Male hypogonadism is defined as the reduction of one or two major testicular functions&#58; spermatogenesis and testosterone production&#46; The etiology of these malfunctions is a primary testicular disease &#40;primary hypogonadism&#41; or disease emerging in the hypothalamus&#47;hypophysis &#40;secondary hypogonadism or hypogonadotropic&#41;&#46; The consensus of the International Society of Andrology&#44; the International Society for the Study of the Aging&#44; the European Association of Urology&#44; the European Academy of Andrology and the American Society of Andrology recognizes the diagnosis of hypogonadism in men with the recurrent presence of total testosterone levels below 8<span class="elsevierStyleHsp" style=""></span>nmol&#47;l &#40;2&#46;3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; When the total testosterone levels range from 8 to 12<span class="elsevierStyleHsp" style=""></span>nmol&#47;l &#40;2&#46;3 and 5&#46;21<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; quantification of free testosterone is useful&#46; Thus&#44; levels of free testosterone below 225<span class="elsevierStyleHsp" style=""></span>pmol&#47;l &#40;65<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; are considered diagnostic and support replacement therapy indication&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> The presence of symptoms of hypogonadism&#44; such as dysthymia&#44; decreased libido&#44; muscle mass and hair is needed to establish the diagnosis&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Testosterone circulates in plasma bound to&#58; albumin&#44; to the sex hormone-binding globulin &#40;SHBG&#41; and free&#46; Therefore&#44; its overall concentration includes these three forms and is subject to variations in albumin levels and SHBG&#44; being an uncertain index of bioavailable testosterone&#46; The optimal method for quantification of free testosterone is a difficult procedure and not available in most clinical laboratories&#46; Thus&#44; the most accepted method of estimating free testosterone is by Vermeulen formula<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> including SHBG&#44; albumin and total testosterone levels&#44; with excellent correlation with the direct determination&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Hypogonadism in the general population</span><p id="par0015" class="elsevierStylePara elsevierViewall">In the general population the prevalence of hypogonadism is from 5 to 12&#46;3&#37; in men aged from 30 to 79&#44; with an incidence of 12&#46;3 per 1000 inhabitants&#47;year&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">3&#44;4</span></a> Testosterone levels change with age&#44; decreasing by 3&#46;5<span class="elsevierStyleHsp" style=""></span>nmol&#47;l &#40;1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; from age 20 to 80&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> In the European Male Aging Study&#44; which included 3220 men aged 40&#8211;79&#44; total testosterone levels decreased by 0&#46;4&#37; annually and free testosterone by 1&#46;3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We should distinguish the common hypogonadism from late onset caused by a functional suppression of the hypothalamic&#8211;pituitary&#8211;testicular axis due to age-related comorbidities&#44; especially obesity&#46; The late-onset hypogonadism has been associated with increased all-cause mortality by up to 5 times&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathophysiology of hypogonadism in diabetes</span><p id="par0025" class="elsevierStylePara elsevierViewall">Several studies have found an inverse relationship between the testosterone levels&#44; insulin resistance and obesity&#46; This relationship can be explained by several hypotheses&#46; First&#44; testosterone is metabolized to 17-beta-estradiol by aromatase located in adipocytes&#46; Due to excess aromatization lower testosterone levels allow increased lipoprotein lipase activity&#44; resulting in increased uptake of fatty acids and triglycerides in the adipocytes&#46; Consequently&#44; there is increased fatty mass which is correlated with higher insulin resistance and lower testosterone levels&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> The second hypothesis suggests that the 17-beta-estradiol and adipokines&#44; interleukin-6&#44; tumor necrosis factor alpha and leptin inhibit the response of the hypothalamic&#8211;pituitary&#8211;testicular axis in response to lower testosterone levels&#46; This impaired homeostatic response explains why some obese men have a hypogonadotropic hypogonadism with normal or low levels of gonadotropins in the presence of low testosterone levels&#46; Furthermore&#44; the insulin resistance is associated with lower testosterone secretion by Leydig cells&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a> Moreover&#44; <span class="elsevierStyleItalic">in vitro</span> studies that have evaluated the direct effect of testosterone in adipocytes show that androgen treatment decreases adipogenesis and increases lipolysis by increasing the number of beta adrenergic receptors&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Prevalence of hypogonadism in diabetes</span><p id="par0030" class="elsevierStylePara elsevierViewall">Patients with type 2 diabetes mellitus &#40;DM2&#41; have shown prevalence of frank hypogonadism &#40;total testosterone levels below 8<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41; from 4&#46;4&#37; to 17&#46;7&#37; and extreme hypogonadism &#40;total testosterone ranging from 8 to 12<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41; from 25&#37; to 32&#46;1&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12&#44;13</span></a> In type 1 diabetes mellitus &#40;DM1&#41; it has been reported that around 7&#46;2&#37; of patients have total testosterone levels below 2&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;&#60;10<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41;&#44; similar to the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> However&#44; up to 20&#37; of patients with DM1 have free testosterone levels below 225<span class="elsevierStyleHsp" style=""></span>pmol&#47;l &#40;65<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41;&#44; higher levels than those described in healthy men and lower than in patients with DM2&#46; Age is the major predictor of low levels of free testosterone&#46; Therefore&#44; for each decade of life the prevalence of this condition is multiplied by two&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Hypogonadotropic hypogonadism and metabolic syndrome</span><p id="par0035" class="elsevierStylePara elsevierViewall">There is a number of factors in different population groups that can lead to androgen deficiency&#44; increasing the prevalence of hypogonadism&#46; These include the characteristic features of the metabolic syndrome such as obesity&#44; hyperglycemia&#44; hypertension and atherogenic dyslipidemia&#46; A large number of epidemiological studies have related testosterone with metabolic syndrome&#44; and its components&#44; individually&#44; have been associated with lower testosterone levels&#46; A Finnish study with 1896 non-diabetic males found lower total and free testosterone figures in those who had metabolic syndrome&#46; Men with free testosterone levels in the lowest tertile showed an increased risk of metabolic syndrome by 2&#46;7 &#40;95&#37; CI&#58; 2&#46;0&#8211;3&#46;7&#41; and 1&#46;7 times &#40;95&#37; CI&#58;1&#46;2&#8211;2&#46;4&#41; after age and body mass index &#40;BMI&#41; adjustment&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a> Conversely&#44; negative associations have been proved between testosterone levels and risk of metabolic syndrome or insulin resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Hypogonadotropic hypogonadism and insulin resistance</span><p id="par0040" class="elsevierStylePara elsevierViewall">Different evidences in healthy men have reported an inverse correlation between total testosterone and insulin&#44; blood sugar and BMI&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9&#44;12&#44;18&#44;19</span></a> Lower testosterone levels have also been reported in first-degree male relatives of patients with diabetes compared to healthy controls&#44; in relation to increased insulin resistance&#44; which in turn means higher risk of developing diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The inverse correlation between total testosterone and insulin is determined by SHBG levels&#44; which are also lower in patients with insulin resistance&#46; Insulin is a key regulator factor on the hepatic production of SHBG&#46; Additionally&#44; it has been reported that men with decreased SHBG levels are at higher risk of developing metabolic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleItalic">In vitro</span> studies have shown that insulin at physiological levels is a powerful inhibitor of SHBG production&#46; This relationship between testosterone and insulin resistance found in healthy individuals has also been confirmed in those with diabetes&#46; There is a significant association between HOMA-IR index with low levels of total testosterone after age and BMI adjustment&#46; Insulin sensitivity was also associated with free testosterone levels&#44; so that individuals with DM2 and lower levels of free testosterone had higher insulin resistance after age and BMI adjustment&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Patients with DM1 are not exempt from presenting metabolic syndrome or insulin resistance&#46; In Europe&#44; several studies show a 30&#8211;40&#37; prevalence of metabolic syndrome in patients with DM1&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22&#8211;24</span></a> Furthermore&#44; the relationship between insulin resistance in patients with DM1 and chronic complications of diabetes&#44; especially microangiopathy&#44;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22&#44;23&#44;25</span></a> has been widely described&#46; Consistent with these results and those obtained in patients with DM2&#44; a direct association has been proved between free and overall testosterone levels and insulin sensitivity in this group of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">14&#44;15</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Hypogonadotropic hypogonadism and dyslipidemia</span><p id="par0055" class="elsevierStylePara elsevierViewall">In several studies a positive correlation has been reported between levels of total and free testosterone with HDL cholesterol and ApoA1 &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;12&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> as well as a negative correlation with total cholesterol&#44; LDL and triglycerides&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> The Massachusetts Male Aging Study&#44; conducted with 1661 men aged from 40 to 70 showed that the relationship between HDL cholesterol and total and free testosterone was most evident in those with cardiovascular disease&#44; where increased 5<span class="elsevierStyleHsp" style=""></span>nmol&#47;l was associated with an increased HDL cholesterol by 6&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">It has also been observed an inverse association between testosterone levels and carotid intima-media thickness in males in cross-sectional studies&#59; in the logistic regression model&#44; after adjustment for cardiovascular risk factors&#44; males with testosterone levels in the lowest quintile &#40;&#60;9<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41; reported a higher risk of being in the top quintile of carotid intima-media thickness&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Finally&#44; longitudinal studies have found an inverse relationship both in total and bioavailable testosterone levels with the progression of aortic atherosclerosis&#46; The Rotterdam study evaluated in 1032 nonsmoker men emergence of aortic atherosclerosis by detecting calcium in the abdominal aorta&#46; It was found that men with levels of total and bioavailable testosterone in the highest tertile had a lower prevalence of severe aortic atherosclerosis &#40;RR&#58; 0&#46;4 &#91;95&#37; CI 0&#46;2&#8211;0&#46;9&#93;&#41;&#44; and also a lower incidence after 6&#46;5 years of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Hypogonadotropic hypogonadism and hypertension</span><p id="par0070" class="elsevierStylePara elsevierViewall">Contrary to what was observed with testosterone levels&#44; blood pressure in men increases with age&#46; In this regard&#44; low testosterone levels have been linked with elevated systolic and diastolic blood pressure&#44; and low testosterone levels have been reported in hypertensive individuals&#46; In the Troms&#248; study&#44; levels of total testosterone and SHBG were associated inversely with systolic blood pressure&#46; Men with systolic blood pressure over 140<span class="elsevierStyleHsp" style=""></span>mm Hg or diastolic pressure over 90<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>Hg had lower levels of total and free testosterone and SHBG after adjustment for BMI&#46; The levels of total testosterone and SHBG were also associated inversely with left ventricular mass&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Testosterone replacement therapy in patients with hypogonadism and diabetes</span><p id="par0075" class="elsevierStylePara elsevierViewall">Several studies have confirmed the beneficial effects of testosterone therapy on insulin sensitivity and obesity markers&#46; Androgen treatment reduces adipogenesis and increases lipolysis&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> There have been favorable anthropometric changes after testosterone replacement therapy&#44; such as a mean 15<span class="elsevierStyleHsp" style=""></span>kg weight reduction&#44; 4&#46;7<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> BMI reduction&#44; 10<span class="elsevierStyleHsp" style=""></span>cm reduction in abdominal girth and up to 5&#46;6&#37; fatty mass lost<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">32&#8211;36</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">As for changes in glucose metabolism after testosterone replacement therapy there has been reduced glycated hemoglobin&#44; fasting glucose&#44; fasting insulin and HOMA-IR index<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">33&#8211;38</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The first randomized&#44; placebo-controlled and crossover clinical trial by Kapoor et al&#46; in 24 patients with DM2 and hypogonadism showed that parenteral administration of testosterone for 3 months produced a significant decreased HOMA-IR index in patients not receiving insulin and lower insulin requirements in patients who were treated with insulin&#46; They also showed significant decreased fasting glucose&#44; glycosylated hemoglobin and fasting insulinemia&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> These findings were replicated in another randomized&#44; placebo-controlled clinical trial in 32 patients with DM2 and hypogonadism treated with transdermal testosterone for 52 weeks&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> and confirmed in the Testosterone Replacement In hypogonadal men with Metabolic Syndrome and&#47;or Type 2 Diabetes clinical trial&#44; with 220 patients participating with hypogonadism and DM2 and&#47;or metabolic syndrome according to the criteria of the International Diabetes Federation&#46; HOMA-IR index was significantly decreased in the group treated with testosterone by 15&#46;2&#37; and 16&#46;4&#37; at 6 and 12 months&#44; respectively&#44; compared with placebo&#44; as well as decreased glycated hemoglobin by 0&#46;4&#37; was observed at 9 months in diabetic patients on hormonal therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">On lipid profile&#44; testosterone replacement therapy has also obtained reduction in total cholesterol&#44; LDL cholesterol&#44; triglycerides and total cholesterol&#47;HDL ratio as well as higher HDL cholesterol<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">34&#44;35&#44;37&#8211;39</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">In studies with smaller sample size the testosterone replacement therapy has shown changes in other markers of cardiovascular risk&#44; such as a significant decrease in carotid intima-media thickness&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a> the number of episodes of angina&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> systolic and diastolic blood pressure&#44; and C-reactive protein &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">One out of 3 patients with type 2 diabetes and&#47;or metabolic syndrome have frank or extreme hypogonadotropic hypogonadism&#46; Because of the increased sedentary lifestyle and obesity&#44; patients with DM1 with a similar type 2 diabetes phenotype&#44; who generally meet diagnostic criteria for metabolic syndrome are becoming more and more frequent&#46; Therefore&#44; patients with DM1 and any component of the metabolic syndrome might also have hypogonadotropic hypogonadism&#46; In this regard&#44; prevalence of decreased levels of free testosterone in individuals with DM1 has been reported as up to 20&#37;&#46; In these patients it is important to establish an early diagnosis of hypogonadism because testosterone replacement therapy has caused&#44; in patients with type 2 diabetes and&#47;or metabolic syndrome&#44; improved cardiometabolic profile&#44; resulting from increased sensitivity to insulin&#46; Currently&#44; no studies are available evaluating the effect of testosterone replacement therapy in individuals with DM1 and hypogonadotropic hypogonadism&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of interests</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:16 [
        0 => array:3 [
          "identificador" => "xres644390"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec657458"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres644389"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec657459"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Hypogonadism in the general population"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Pathophysiology of hypogonadism in diabetes"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Prevalence of hypogonadism in diabetes"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Hypogonadotropic hypogonadism and metabolic syndrome"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Hypogonadotropic hypogonadism and insulin resistance"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Hypogonadotropic hypogonadism and dyslipidemia"
        ]
        11 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Hypogonadotropic hypogonadism and hypertension"
        ]
        12 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Testosterone replacement therapy in patients with hypogonadism and diabetes"
        ]
        13 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conclusions"
        ]
        14 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conflict of interests"
        ]
        15 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-04-14"
    "fechaAceptado" => "2015-06-09"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec657458"
          "palabras" => array:3 [
            0 => "Hypogonadism"
            1 => "Testosterone deficiency"
            2 => "Hypogonadism and diabetes"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec657459"
          "palabras" => array:3 [
            0 => "Hipogonadismo"
            1 => "D&#233;ficit de testosterona"
            2 => "Hipogonadismo y diabetes"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Testosterone deficiency in adult age is associated with a decrease in libido&#44; energy&#44; hematocrit&#44; muscle mass and bone mineral density&#44; as well as with depression&#46; More recently&#44; testosterone deficiency has also been associated with various components of the metabolic syndrome&#44; which in turn is associated with a five-fold increase in the risk of cardiovascular disease&#46; Low testosterone levels are associated with increased insulin resistance&#44; increase in fat mass&#44; low HDL cholesterol&#44; higher triglyceride levels and hypertension&#46; Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and&#47;or metabolic syndrome has shown reductions in insulin resistance&#44; total cholesterol&#44; LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El d&#233;ficit de testosterona en la edad adulta se relaciona con depresi&#243;n&#44; disminuci&#243;n de la libido&#44; energ&#237;a&#44; hematocrito&#44; masa muscular y de la densidad mineral &#243;sea&#46; En los &#250;ltimos a&#241;os&#44; tambi&#233;n se ha asociado con diversos componentes del s&#237;ndrome metab&#243;lico&#44; que a su vez se relacionan con un aumento de hasta 5 veces en el riesgo de enfermedad cardiovascular&#46; As&#237;&#44; las concentraciones bajas de testosterona se asocian con una mayor resistencia a la insulina&#44; incremento de la masa grasa&#44; colesterol HDL bajo&#44; triglic&#233;ridos elevados e hipertensi&#243;n arterial&#46; Inversamente&#44; el tratamiento sustitutivo en pacientes con d&#233;ficit de testosterona y diabetes mellitus tipo 2 y&#47;o s&#237;ndrome metab&#243;lico ha demostrado reducciones en la resistencia a la insulina&#44; colesterol total&#44; LDL y triglic&#233;ridos&#44; y una mejor&#237;a del control gluc&#233;mico y los par&#225;metros antropom&#233;tricos&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Fern&#225;ndez-Mir&#243; M&#44; Chillar&#243;n JJ&#44; Pedro-Botet J&#46; D&#233;ficit de testosterona&#44; s&#237;ndrome metab&#243;lico y diabetes mellitus&#46; Med Clin &#40;Barc&#41;&#46; 2016&#59;146&#58;69&#8211;73&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&#46;1<span class="elsevierStyleHsp" style=""></span>kg in 5 years<br>&#8722;15&#46;35<span class="elsevierStyleHsp" style=""></span>kg in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yassin et Doros<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a><br>Saad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;4&#46;77<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Saad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abdominal girth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;63<span class="elsevierStyleHsp" style=""></span>cm in 3 months<br>&#8722;10<span class="elsevierStyleHsp" style=""></span>cm in 12 months<br>&#8722;8&#46;5<span class="elsevierStyleHsp" style=""></span>cm in 5 years<br>&#8722;9&#46;4<span class="elsevierStyleHsp" style=""></span>cm in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kapoor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a><br>Heufelder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a><br>Saad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a><br>Yassin et Doros<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Waist&#47;hip ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;96&#37; in 3 months<br>&#8722;0&#46;03 in 3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Boyanov et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a><br>Kapoor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fatty mass&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;5&#46;65&#37; in 3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Boyanov et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1062187.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Anthropometric changes after testosterone replacement therapy in patients with hypogonadism&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glycosylated hemoglobin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;8&#37; in 3 months<br>&#8722;0&#46;37&#37; in 3 months<br>&#8722;0&#46;8&#37; in 12 months<br>&#8722;0&#46;44&#37; in 12 months<br>&#8722;2&#46;48&#37; in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Boyanov et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a><br>Kapoor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a><br>Heufelder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a><br>Jones et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a><br>Saad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fasting glucose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;58<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 3 months<br>&#8722;1&#46;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kapoor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a><br>Saad et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fasting insulinemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;40&#46;2<span class="elsevierStyleHsp" style=""></span>pmol&#47;l in 12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heufelder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HOMA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;73 in 3 months<br>&#8722;0&#46;9 in 12 months<br>&#8722;16&#46;4&#37; in 12 months<br>&#8722;0&#46;6 in 3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kapoor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a><br>Heufelder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a><br>Jones et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a><br>Cornoldi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1062188.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Changes in glucose metabolism after testosterone replacement therapy in hypogonadal patients&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">HDL&#44; high-density lipoprotein&#59; LDL&#44; low-density lipoprotein&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 3 months<br>&#8722;0&#46;28<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 12 months<br>&#8722;2&#46;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 5 years<br>&#8722;0&#46;44<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kapoor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a><br>Jones et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a><br>Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a><br>Cornoldi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDL cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;16<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 12 months<br>&#8722;1&#46;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Jones et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a><br>Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;0&#46;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heufelder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglycerides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;7<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 12 months<br>&#8722;0&#46;36<span class="elsevierStyleHsp" style=""></span>mmol&#47;l<br>&#8722;0&#46;9<span class="elsevierStyleHsp" style=""></span>mmol&#47;l in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heufelder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a><br>Cornoldi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a><br>Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total choleesterol&#47;HDL ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;95 in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1062189.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Changes in lipid profile after testosterone replacement therapy in patients with hypogonadism&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Primary outcome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Carotid intima-media thickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduction&#46; &#8722;0&#46;22<span class="elsevierStyleHsp" style=""></span>mm at 12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aversa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of angina episodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduction by 34&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cornoldi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C-reactive protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;5&#46;26<span class="elsevierStyleHsp" style=""></span>U&#47;l in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;15<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>Hg in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diastolic blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;9<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>Hg in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aspartate aminotransferase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;22<span class="elsevierStyleHsp" style=""></span>U&#47;l in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alanine aminotransferase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;23&#46;34<span class="elsevierStyleHsp" style=""></span>U&#47;l in 5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Traish et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1062190.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Changes in other markers of cardiovascular risk after testosterone replacement therapy in patients with hypogonadism&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:40 [
            0 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Investigation&#44; treatment&#44; and monitoring of late-onset hypogonadism in males&#58; ISA&#44; ISSAM&#44; EAU&#44; EAA&#44; and ASA recommendations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Wang"
                            1 => "E&#46; Nieschlag"
                            2 => "R&#46; Swerdloff"
                            3 => "H&#46;M&#46; Behre"
                            4 => "W&#46;J&#46; Hellstrom"
                            5 => "L&#46;J&#46; Gooren"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2164/jandrol.108.006486"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Androl"
                        "fecha" => "2009"
                        "volumen" => "30"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18772485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A critical evaluation of simple methods for the estimation of free testosterone in serum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Vermeulen"
                            1 => "L&#46; Verdonck"
                            2 => "J&#46;M&#46; Kaufman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem.84.10.6079"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "1999"
                        "volumen" => "84"
                        "paginaInicial" => "3666"
                        "paginaFinal" => "3672"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10523012"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence and incidence of androgen deficiency in middle-aged and older men&#58; estimates from the Massachusetts Male Aging Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;B&#46; Araujo"
                            1 => "A&#46;B&#46; O&#8217;Donnell"
                            2 => "D&#46;J&#46; Brambilla"
                            3 => "W&#46;B&#46; Simpson"
                            4 => "C&#46; Longcope"
                            5 => "A&#46;M&#46; Matsumoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2003-031719"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2004"
                        "volumen" => "89"
                        "paginaInicial" => "5920"
                        "paginaFinal" => "5926"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15579737"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of symptomatic androgen deficiency in men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;B&#46; Araujo"
                            1 => "G&#46;R&#46; Esche"
                            2 => "V&#46; Kupelian"
                            3 => "A&#46;B&#46; O¿Donnell"
                            4 => "T&#46;G&#46; Travison"
                            5 => "R&#46;E&#46; Williams"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2007-1245"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2007"
                        "volumen" => "92"
                        "paginaInicial" => "4241"
                        "paginaFinal" => "4247"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17698901"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0021915014013513"
                          "estado" => "S300"
                          "issn" => "00219150"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age differences in serum androgen levels in normal adult males"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46;E&#46; Purifoy"
                            1 => "L&#46;H&#46; Koopmans"
                            2 => "D&#46;M&#46; Mayes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Biol"
                        "fecha" => "1981"
                        "volumen" => "53"
                        "paginaInicial" => "499"
                        "paginaFinal" => "511"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7199020"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypothalamic&#8211;pituitary&#8211;testicular axis disruptions in older men are differentially linked to age and modifiable risk factors&#58; The European Male Aging Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;C&#46; Wu"
                            1 => "A&#46; Tajar"
                            2 => "S&#46;R&#46; Pye"
                            3 => "A&#46;J&#46; Silman"
                            4 => "J&#46;D&#46; Finn"
                            5 => "T&#46;W&#46; O&#8217;Neill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2007-1972"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2008"
                        "volumen" => "93"
                        "paginaInicial" => "2737"
                        "paginaFinal" => "2745"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18270261"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Late-onset hypogonadism and mortality in aging men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;R&#46; Pye"
                            1 => "I&#46;T&#46; Huhtaniemi"
                            2 => "J&#46;D&#46; Finn"
                            3 => "D&#46;M&#46; Lee"
                            4 => "T&#46;W&#46; O&#8217;Neill"
                            5 => "A&#46; Tajar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2013-2052"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2014"
                        "volumen" => "99"
                        "paginaInicial" => "1357"
                        "paginaFinal" => "1366"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24423283"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The hypogonadal-obesity cycle&#58; role of aromatase in modulating the testosterone-estradiol shunt&#8212;a major factor in the genesis of morbid obesity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;G&#46; Cohen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1054/mehy.1997.0624"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Hypotheses"
                        "fecha" => "1999"
                        "volumen" => "52"
                        "paginaInicial" => "49"
                        "paginaFinal" => "51"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10342671"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Pitteloud"
                            1 => "M&#46; Hardin"
                            2 => "A&#46;A&#46; Dwyer"
                            3 => "E&#46; Valassi"
                            4 => "M&#46; Yialama"
                            5 => "D&#46; Elahi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2004-2190"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2005"
                        "volumen" => "90"
                        "paginaInicial" => "2636"
                        "paginaFinal" => "2641"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15713702"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The adipose tissue metabolism&#58; role of testosterone and dehydroepiandrosterone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "G&#46; De Pergola"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Obes Relat Metab Disord"
                        "fecha" => "2000"
                        "volumen" => "24"
                        "paginaInicial" => "S59"
                        "paginaFinal" => "S63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10997611"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Androgens and body fat distribution"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Blouin"
                            1 => "A&#46; Boivin"
                            2 => "A&#46; Tchernof"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jsbmb.2007.09.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Steroid Biochem Mol Biol"
                        "fecha" => "2008"
                        "volumen" => "108"
                        "paginaInicial" => "272"
                        "paginaFinal" => "280"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17945484"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Screening for hypogonadism in diabetes 2008&#47;9&#58; results from the Cheshire Primary Care cohort"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;G&#46; Anderson"
                            1 => "A&#46; Heald"
                            2 => "N&#46; Younger"
                            3 => "S&#46; Bujawansa"
                            4 => "R&#46;P&#46; Narayanan"
                            5 => "A&#46; McCulloch"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pcd.2011.07.006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Prim Care Diabetes"
                        "fecha" => "2012"
                        "volumen" => "6"
                        "paginaInicial" => "143"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21982717"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673611607848"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes&#58; correlations with bioavailable testosterone and visceral adiposity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Kappor"
                            1 => "H&#46; Aldred"
                            2 => "S&#46; Clark"
                            3 => "K&#46;S&#46; Channer"
                            4 => "T&#46;H&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc06-1426"
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2007"
                        "volumen" => "30"
                        "paginaInicial" => "911"
                        "paginaFinal" => "917"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17392552"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age&#44; insulin requirements&#44; waist circumference and triglycerides predict hypogonadotropic hypogonadism in patients with type 1 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Chillar&#243;n"
                            1 => "M&#46; Fern&#225;ndez-Mir&#243;"
                            2 => "M&#46; Albareda"
                            3 => "L&#46; Vila"
                            4 => "C&#46; Colom"
                            5 => "S&#46; Fontser&#232;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jsm.12748"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Sex Med"
                        "fecha" => "2015"
                        "volumen" => "12"
                        "paginaInicial" => "76"
                        "paginaFinal" => "82"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25394376"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low testosterone levels are common and associated with insulin resistance in men with diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Grossmann"
                            1 => "M&#46;C&#46; Thomas"
                            2 => "S&#46; Panagiotopoulos"
                            3 => "K&#46; Sharpe"
                            4 => "R&#46;J&#46; Macisaac"
                            5 => "S&#46; Clarke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2007-2177"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2008"
                        "volumen" => "93"
                        "paginaInicial" => "1834"
                        "paginaFinal" => "1840"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18319314"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sex hormones&#44; inflammation and the metabolic syndrome&#58; a population-based study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;E&#46; Laaksonen"
                            1 => "L&#46; Niskanen"
                            2 => "K&#46; Punnonen"
                            3 => "K&#46; Nyyss&#246;nen"
                            4 => "T&#46;P&#46; Tuomainen"
                            5 => "R&#46; Salonen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2003"
                        "volumen" => "149"
                        "paginaInicial" => "601"
                        "paginaFinal" => "608"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14641004"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Contribution of age and declining androgen levels to features of the metabolic syndrome in men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Blouin"
                            1 => "J&#46;P&#46; Despr&#233;s"
                            2 => "C&#46; Couillard"
                            3 => "A&#46; Tremblay"
                            4 => "D&#46; Prud&#8217;homme"
                            5 => "C&#46; Bouchard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.metabol.2005.03.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Metabolism"
                        "fecha" => "2005"
                        "volumen" => "54"
                        "paginaInicial" => "1034"
                        "paginaFinal" => "1040"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16092053"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Can clinical factors estimate insulin resistance in type 1 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46;V&#46; Williams"
                            1 => "J&#46;R&#46; Erbey"
                            2 => "D&#46; Becker"
                            3 => "S&#46; Arslanian"
                            4 => "T&#46;J&#46; Orchard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Diabetes"
                        "fecha" => "2000"
                        "volumen" => "49"
                        "paginaInicial" => "626"
                        "paginaFinal" => "632"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10871201"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S073510971302086X"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between plasma testosterone and cardiovascular risk factors in healthy adult men&#58; The Telecom Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Simon"
                            1 => "M&#46;A&#46; Charles"
                            2 => "K&#46; Nahoul"
                            3 => "G&#46; Orssaud"
                            4 => "J&#46; Kremski"
                            5 => "V&#46; Hully"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem.82.2.3766"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "1997"
                        "volumen" => "82"
                        "paginaInicial" => "682"
                        "paginaFinal" => "685"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9024276"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Androgens&#44; insulin resistance and vascular disease in men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Kappor"
                            1 => "C&#46;J&#46; Malkin"
                            2 => "K&#46;S&#46; Channer"
                            3 => "T&#46;H&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Endocrinol &#40;Oxf&#41;"
                        "fecha" => "2005"
                        "volumen" => "63"
                        "paginaInicial" => "239"
                        "paginaFinal" => "250"
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109710002809"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aging&#44; androgens&#44; and the metabolic syndrome in a longitudinal study of aging"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Rodriguez"
                            1 => "D&#46;C&#46; Muller"
                            2 => "E&#46;J&#46; Metter"
                            3 => "M&#46; Maggio"
                            4 => "S&#46;M&#46; Harman"
                            5 => "M&#46;R&#46; Blackman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2006-2764"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2007"
                        "volumen" => "92"
                        "paginaInicial" => "3568"
                        "paginaFinal" => "3572"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17595254"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome in type 1 diabetes&#58; association with diabetic nephropathy and glycemic control &#40;the FinnDiane study&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;M&#46; Thorn"
                            1 => "C&#46; Forsblom"
                            2 => "J&#46; Fagerudd"
                            3 => "M&#46;C&#46; Thomas"
                            4 => "K&#46; Pettersson-Fernholm"
                            5 => "M&#46; Saraheimo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2005"
                        "volumen" => "28"
                        "paginaInicial" => "2019"
                        "paginaFinal" => "2024"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16043748"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes&#58; results from Metascreen&#44; a multicenter diabetes clinic-based survey"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "The Metascreen Writing Committee"
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Bonadonna"
                            1 => "D&#46; Cucinotta"
                            2 => "D&#46; Fedele"
                            3 => "G&#46; Riccardi"
                            4 => "A&#46; Tiengo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc06-0942"
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2006"
                        "volumen" => "29"
                        "paginaInicial" => "2701"
                        "paginaFinal" => "2707"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17130208"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome and type-1 diabetes mellitus&#58; prevalence and associated factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Chillar&#243;n"
                            1 => "J&#46;A&#46; Flores-Le-Roux"
                            2 => "A&#46; Goday"
                            3 => "D&#46; Benaiges"
                            4 => "M&#46;J&#46; Carrera"
                            5 => "J&#46; Puig"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Cardiol"
                        "fecha" => "2010"
                        "volumen" => "63"
                        "paginaInicial" => "423"
                        "paginaFinal" => "429"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20334808"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estimated glucose disposal rate in assessment of the metabolic syndrome and microvascular complications in patients with type 1 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Chillar&#243;n"
                            1 => "A&#46; Goday"
                            2 => "J&#46; Flores-Le-Roux"
                            3 => "D&#46; Benaiges"
                            4 => "M&#46;J&#46; Carrera"
                            5 => "J&#46; Puig"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2009-0960"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2009"
                        "volumen" => "94"
                        "paginaInicial" => "3530"
                        "paginaFinal" => "3534"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19584183"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46; Van Pottelbergh"
                            1 => "L&#46; Braeckman"
                            2 => "D&#46; de Bacquer"
                            3 => "G&#46; de Backer"
                            4 => "J&#46;M&#46; Kaufman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Atherosclerosis"
                        "fecha" => "2003"
                        "volumen" => "166"
                        "paginaInicial" => "95"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12482555"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The relationship between endogenous testosterone and lipid profile in middle-aged and elderly Chinese men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Zhang"
                            1 => "H&#46; Zhang"
                            2 => "X&#46; Zhang"
                            3 => "B&#46; Zhang"
                            4 => "F&#46; Wang"
                            5 => "C&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1530/EJE-13-0802"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2014"
                        "volumen" => "170"
                        "paginaInicial" => "487"
                        "paginaFinal" => "494"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24394726"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Higher testosterone levels are associated with increased high-density lipoprotein cholesterol in men with cardiovascular disease&#58; results from the Massachusetts Male Aging Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46;T&#46; Page"
                            1 => "B&#46;A&#46; Mohr"
                            2 => "C&#46;L&#46; Link"
                            3 => "A&#46;B&#46; O&#8217;Donnell"
                            4 => "W&#46;J&#46; Bremner"
                            5 => "J&#46;B&#46; McKinlay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1745-7262.2008.00332.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Asian J Androl"
                        "fecha" => "2008"
                        "volumen" => "10"
                        "paginaInicial" => "193"
                        "paginaFinal" => "200"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18097527"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109703001876"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low testosterone levels are associated with carotid atherosclerosis in men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Svartberg"
                            1 => "D&#46; von M&#252;hlen"
                            2 => "E&#46; Mathiesen"
                            3 => "O&#46; Joakimsen"
                            4 => "K&#46;H&#46; B&#248;naa"
                            5 => "E&#46; Stensland-Bugge"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2796.2006.01637.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Intern Med"
                        "fecha" => "2006"
                        "volumen" => "259"
                        "paginaInicial" => "576"
                        "paginaFinal" => "582"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16704558"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men&#58; The Rotterdam study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;E&#46; Hak"
                            1 => "J&#46;C&#46; Witteman"
                            2 => "F&#46;H&#46; de Jong"
                            3 => "M&#46;I&#46; Geerlings"
                            4 => "A&#46; Hofman"
                            5 => "H&#46;A&#46; Pols"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem.87.8.8762"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2002"
                        "volumen" => "87"
                        "paginaInicial" => "3632"
                        "paginaFinal" => "3639"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12161487"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of endogenous testosterone with blood pressure and left ventricular mass in men&#46; The Troms&#248; Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Svartberg"
                            1 => "D&#46; von M&#252;hlen"
                            2 => "H&#46; Schirmer"
                            3 => "E&#46; Barrett-Connor"
                            4 => "J&#46; Sundfjord"
                            5 => "R&#46; Jorde"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2004"
                        "volumen" => "150"
                        "paginaInicial" => "65"
                        "paginaFinal" => "71"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14713281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Testosterone theraphy in hypogonadal men results in sustained and clinically meaningful weight loss"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Yassin"
                            1 => "G&#46; Doros"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/cob.12022"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Obes"
                        "fecha" => "2013"
                        "volumen" => "3"
                        "paginaInicial" => "73"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24163704"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46; Saad"
                            1 => "A&#46; Haider"
                            2 => "G&#46; Doros"
                            3 => "A&#46; Traish"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Obesity &#40;Silver Spring&#41;"
                        "fecha" => "2013"
                        "volumen" => "21"
                        "paginaInicial" => "1975"
                        "paginaFinal" => "1981"
                        "itemHostRev" => array:3 [
                          "pii" => "S0002934313009273"
                          "estado" => "S300"
                          "issn" => "00029343"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Testosterone replacement therapy improves insulin resistance&#44; glycaemic control&#44; visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Kapoor"
                            1 => "E&#46; Goodwin"
                            2 => "K&#46;S&#46; Channer"
                            3 => "T&#46;H&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1530/eje.1.02166"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2006"
                        "volumen" => "154"
                        "paginaInicial" => "899"
                        "paginaFinal" => "906"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16728551"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycaemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;E&#46; Heufelder"
                            1 => "F&#46; Saad"
                            2 => "M&#46;C&#46; Bunck"
                            3 => "L&#46; Gooren"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2164/jandrol.108.007005"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Androl"
                        "fecha" => "2009"
                        "volumen" => "30"
                        "paginaInicial" => "726"
                        "paginaFinal" => "733"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19578132"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Testosterone supplemetation in men with type 2 diabetes&#44; visceral obesity and partial androgen deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;A&#46; Boyanov"
                            1 => "Z&#46; Boneva"
                            2 => "V&#46;G&#46; Christov"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aging Male"
                        "fecha" => "2003"
                        "volumen" => "6"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12809074"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Testosterone replacement in hypogonadal men with type 2 diabetes and&#47;or metabolic syndrome &#40;the TIMES2 study&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;H&#46; Jones"
                            1 => "S&#46; Arver"
                            2 => "H&#46;M&#46; Behre"
                            3 => "J&#46; Buvat"
                            4 => "E&#46; Meuleman"
                            5 => "I&#46; Moncada"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc10-1233"
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2001"
                        "volumen" => "34"
                        "paginaInicial" => "828"
                        "paginaFinal" => "837"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21386088"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of chronic testosterone administration on myocardial ischemia&#44; lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Cornoldi"
                            1 => "G&#46; Caminiti"
                            2 => "G&#46; Marazzi"
                            3 => "C&#46; Vitale"
                            4 => "R&#46; Patrizi"
                            5 => "M&#46; Volterrani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijcard.2008.12.107"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cardiol"
                        "fecha" => "2010"
                        "volumen" => "142"
                        "paginaInicial" => "50"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19361872"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome&#58; an observational&#44; long-term registry study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;M&#46; Traish"
                            1 => "A&#46; Haider"
                            2 => "G&#46; Doros"
                            3 => "F&#46; Saad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ijcp.12319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Clin Pract"
                        "fecha" => "2014"
                        "volumen" => "68"
                        "paginaInicial" => "314"
                        "paginaFinal" => "329"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24127736"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome&#58; results from a 24-month&#44; randomized&#44; double-blind&#44; placebo-controlled study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Aversa"
                            1 => "R&#46; Bruzziches"
                            2 => "D&#46; Francomano"
                            3 => "G&#46; Rosano"
                            4 => "A&#46;M&#46; Isidori"
                            5 => "A&#46; Lenzi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1743-6109.2010.01931.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Sex Med"
                        "fecha" => "2010"
                        "volumen" => "7"
                        "paginaInicial" => "3495"
                        "paginaFinal" => "3503"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20646185"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301395/v1_201605240650/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "43313"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Reviews"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014600000002/v1_201605240650/S2387020616301395/v1_201605240650/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301395?idApp=UINPBA00004N"
]