Letter to the Editor
Secondary hypercupremia due to oral contraceptive use
Hipercupremia secundaria a toma de anticonceptivos orales
Alejandro Maceín Rodríguez
, Andrea Valcárcel Alonso
Corresponding author
Servicio de Medicina Interna, Hospital Clínico San Carlos, Madrid, Spain
Read
Not available
Timeswas read the article
Total PDF
Total HTML
Share statistics
array:24 [ "pii" => "S2387020624002043" "issn" => "23870206" "doi" => "10.1016/j.medcle.2023.11.036" "estado" => "S300" "fechaPublicacion" => "2024-06-14" "aid" => "6540" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2024" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2024;162:560-1" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775324000241" "issn" => "00257753" "doi" => "10.1016/j.medcli.2023.11.043" "estado" => "S300" "fechaPublicacion" => "2024-06-14" "aid" => "6540" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2024;162:560-1" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Hipercupremia secundaria a toma de anticonceptivos orales" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "560" "paginaFinal" => "561" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Secondary hypercupremia due to oral contraceptive use" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alejandro Maceín Rodríguez, Andrea Valcárcel Alonso" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Maceín Rodríguez" ] 1 => array:2 [ "nombre" => "Andrea" "apellidos" => "Valcárcel Alonso" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020624002043" "doi" => "10.1016/j.medcle.2023.11.036" "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/S2387020624002043?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324000241?idApp=UINPBA00004N" "url" => "/00257753/0000016200000011/v1_202406011140/S0025775324000241/v1_202406011140/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020624002055" "issn" => "23870206" "doi" => "10.1016/j.medcle.2023.11.037" "estado" => "S300" "fechaPublicacion" => "2024-06-14" "aid" => "6542" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2024;162:561-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Mesenteric panniculitis simulating early lymphoma recurrence" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "561" "paginaFinal" => "563" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Paniculitis mesentérica como simuladora de recidiva de un linfoma" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2616 "Ancho" => 2007 "Tamanyo" => 353457 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">PET-CT comparison. A) Before chemotherapy, B) after the first cycle of antibiotic therapy, C) after the second cycle of chemotherapy and D) in follow-up after chemotherapy.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jaime Gil-Rodríguez, José-Luis Callejas-Rubio, Paloma García Martín" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Jaime" "apellidos" => "Gil-Rodríguez" ] 1 => array:2 [ "nombre" => "José-Luis" "apellidos" => "Callejas-Rubio" ] 2 => array:2 [ "nombre" => "Paloma" "apellidos" => "García Martín" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775324000265" "doi" => "10.1016/j.medcli.2023.11.045" "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/S0025775324000265?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624002055?idApp=UINPBA00004N" "url" => "/23870206/0000016200000011/v1_202406091353/S2387020624002055/v1_202406091353/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020624002031" "issn" => "23870206" "doi" => "10.1016/j.medcle.2023.11.035" "estado" => "S300" "fechaPublicacion" => "2024-06-14" "aid" => "6539" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2024;162:559-60" "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">Letter to the Editor</span>" "titulo" => "Percutaneous approach to complications associated with the use of a subcutaneous venous reservoir" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "559" "paginaFinal" => "560" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Abordaje percutáneo de las complicaciones asociadas al empleo de reservorio venoso subcutáneo" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Zoser Saura Carretero, José Abellán Huerta, Pedro Cano Vivar" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Zoser" "apellidos" => "Saura Carretero" ] 1 => array:2 [ "nombre" => "José" "apellidos" => "Abellán Huerta" ] 2 => array:2 [ "nombre" => "Pedro" "apellidos" => "Cano Vivar" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S002577532400023X" "doi" => "10.1016/j.medcli.2023.11.042" "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/S002577532400023X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624002031?idApp=UINPBA00004N" "url" => "/23870206/0000016200000011/v1_202406091353/S2387020624002031/v1_202406091353/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Secondary hypercupremia due to oral contraceptive use" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor,</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "560" "paginaFinal" => "561" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Alejandro Maceín Rodríguez, Andrea Valcárcel Alonso" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Alejandro" "apellidos" => "Maceín Rodríguez" "email" => array:1 [ 0 => "alejandromacein@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Andrea" "apellidos" => "Valcárcel Alonso" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital Clínico San Carlos, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipercupremia secundaria a toma de anticonceptivos orales" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Increased serum copper concentration (hypercupraemia) can have various causes: inflammatory conditions, Wilson's disease, infections, environmental exposures and neoplasms, among others. In addition, physiological conditions such as pregnancy or taking oral contraceptives are described as causes of such elevation.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 21-year-old woman, with no medical history of interest, under treatment with oral contraceptives (dienogest/estradiol) for dysmenorrhoea who was referred to the internal medicine department for a 9-month history of non-specific asthenia, general malaise, nausea, vomiting and blurred vision. Physical examination was unremarkable. Laboratory results revealed iron deficiency anaemia, probably related to menorrhagia and vitamin B<span class="elsevierStyleInf">12</span> deficiency, and supplementation of both was started. An ultrasound scan of the abdomen and a gastroscopy were requested, both of which were normal.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The clinical manifestations persisted after 3 months, so the laboratory study was extended, showing an increase in plasma copper of 2.06 mg/l (0.8–1.55) and ceruloplasmin of 44 mg/dl (20–40). Liver function, autoimmunity study and urine copper levels were normal.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In subsequent re-evaluations, the patient was asymptomatic, with hypercupraemia persisting in the control lab tests (copper of 2.42 mg/l). In view of the suspicion of hypercupraemia secondary to taking contraceptives, this treatment was withdrawn, and copper levels returned to normal in 3 weeks. An ophthalmological study was also performed, which ruled out corneal copper deposition. After withdrawal of contraceptive treatment, the patient had dysmenorrhoea, so treatment was started with a progestogen (drospirenone), and copper levels remained normal in subsequent check-ups.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Copper is a trace element mainly bound to ceruloplasmin but can also be found bound to albumin or free in plasma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Copper concentrations increase during menstruation and decrease during ovulation. Oestrogens increase the concentration of ceruloplasmin in a non-dose-dependent manner, so they intervene in copper metabolism and can increase copper concentrations in the blood.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The progestogens included in birth control pills (BCPs) also seem to influence copper metabolism, with the increase in cupremia being more marked in those cases that include progestogens with an anti-androgenic effect.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> However, the decrease in the concentration of these, together with a greater anti-estrogenic effect in the latest generation BCPs could be related to the exponential reduction in copper levels secondary to BCP intake observed over the years.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> This could explain why, in our patient, switching to a third-generation progestogen with such characteristics maintained normal copper values afterwards.</p><p id="par0030" class="elsevierStylePara elsevierViewall">BCPs are considered a classic cause of hypercupremia,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> despite the fact that it is usually not reflected in the technical data sheet. There are several case series in the medical literature, some of which have shown corneal copper deposits in the form of rings.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Hypercupraemia in relation to BCPs does not usually exceed 2 mg/l, although our patient maintained copper levels above this figure, and symptoms of toxicity usually appear with copper values above 3 mg/l and can be lethal above 5 mg/l.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The long-term clinical impact of mild elevations in cupremia in association with BCPs is unknown, although the association between hypercupraemia and coronary heart disease and myocardial infarction has been demonstrated.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The time of exposure to BCPs necessary to develop hypercupraemia is also not established, nor is the time after discontinuation of treatment to restore normal serum copper levels.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In our case, taking into account the increase in copper concentration after the administration of contraceptives, the association already described in the medical literature, the return to normal blood copper levels after discontinuation of treatment and the absence of other contributing factors, hypercupraemia could be attributed to contraceptive treatment as a probable cause (6 points) using Naranjo's causality algorithm. However, it is not clear whether the patient's non-specific symptoms at the start of follow-up, which progressively resolved, could be related to this laboratory abnormality.</p><p id="par0045" class="elsevierStylePara elsevierViewall">There is insufficient evidence to recommend copper determination in all patients treated with BCPs, although this aetiology should be considered in women treated with BCPs who develop hypercupraemia, or where there is evidence of copper toxicity (liver disease, neurological alterations and digestive symptoms, among others) and then consider withdrawal of treatment taking into account the limited data available.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Patient authorisation</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that their health centre's protocols for access to medical records have been followed in order to prepare this research publication for dissemination to the scientific community. In addition, the verbal informed consent of the patient has also been obtained.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">No organisation has funded this research.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no financial or personal relationship with other persons or organisations that could give rise to a conflict of interest in relation to the article submitted for publication.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Patient authorisation" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypercupremia secondary to oral contraceptives: Report of 2 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Araujo" 1 => "L. Prieto" 2 => "C. Izquierdo" 3 => "B. Oliván" 4 => "R. Campos Del Portillo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.endinu.2017.08.002" "Revista" => array:6 [ "tituloSerie" => "Endocrinol Diabetes Nutr" "fecha" => "2017" "volumen" => "64" "paginaInicial" => "509" "paginaFinal" => "511" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29050708" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relevance of serum copper elevation induced by oral contraceptives: A meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Ž Babić" 1 => "B. Tariba" 2 => "J. Kovačić" 3 => "A. Pizent" 4 => "V.M. Varnai" 5 => "J. Macan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.contraception.2012.10.006" "Revista" => array:6 [ "tituloSerie" => "Contraception" "fecha" => "2013" "volumen" => "87" "paginaInicial" => "790" "paginaFinal" => "800" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23153894" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of oral contraceptive progestins on serum copper concentration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Berg" 1 => "L. Kohlmeier" 2 => "H. Brenner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ejcn.1600631" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Nutr" "fecha" => "1998" "volumen" => "52" "paginaInicial" => "711" "paginaFinal" => "715" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9805216" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Corneal copper deposition secondary to oral contraceptives" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Garmizo" 1 => "B.J. Frauens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/OPX.0b013e3181853092" "Revista" => array:5 [ "tituloSerie" => "Optom Vis Sci" "fecha" => "2008" "volumen" => "85" "paginaInicial" => "802" "paginaFinal" => "807" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum copper concentration and coronary heart disease among US adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E.S. Ford" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/oxfordjournals.aje.a010168" "Revista" => array:6 [ "tituloSerie" => "Am J Epidemiol" "fecha" => "2000" "volumen" => "151" "paginaInicial" => "1182" "paginaFinal" => "1188" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10905530" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000016200000011/v1_202406091353/S2387020624002043/v1_202406091353/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000016200000011/v1_202406091353/S2387020624002043/v1_202406091353/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624002043?idApp=UINPBA00004N" ]
