Información del artículo
El enfoque terapéutico tradicional del síndrome del ovario poliquístico (SOP) es de tipo sintomático. Sin embargo, las mujeres con SOP presentan a menudo diversas anomalías metabólicas, y cada vez hay más pruebas de que pueden presentar posteriormente un mayor riesgo cardiovascular y otros problemas médicos importantes. La resistencia a la insulina, la hiperinsulinemia asociada y el exceso de andrógenos desempeñan, al parecer, un papel central en la patogenia del SOP. En muchas pacientes, la atenuación de la resistencia a la insulina puede influir en todo el espectro de anomalies endocrinas, metabólicas y reproductoras del SOP. Además, los fármacos antiandrogénicos no sólo constituyen, al parecer, un elemento eficaz en el tratamiento sintomático del SOP, sino también un posible tratamiento patogénico, como lo sugieren los cambios favorables que se producen en la composición corporal y en las características metabólicas de las mujeres con SOP que los utilizan.
Palabras clave:
Síndrome del ovario poliquístico
Resistencia a la insulina
Hiperandrogenismo
Agentes sensibilizantes a la insulina
Fármacos antiandrogénicos
Metformina
Tiazolidinadionas
Flutamida
The traditional therapeutic approach to polycystic ovary syndrome (PCOS) is symptomatic. However, PCOS women often show several metabolic abnormalities, and there is growing evidence that these women may have increased cardiovascular risk and other major medical outcomes later in life. Insulin resistance with associated hyperinsulinemia and androgen excess seem to play a central role in the pathogenesis of PCOS. Consistently, attenuation of insulin resistance may affect the entire spectrum of endocrine, metabolic and reproductive abnormalities of PCOS in many subjects. Furthermore, antiandrogen drugs seem to be not only an effective tool in the symptomatic treatment of PCOS, but also a potential pathogenetic therapy, as suggested by the favourable changes of body composition and metabolic features reported using these drugs in PCOS women.
Key words:
Polycystic ovary syndrome
Insulin resistance
Hyperandrogenism
Insulin sensitizing agents
Antiandrogen drugs
Metformin
Thiazolidinediones
Flutamide
El Texto completo está disponible en PDF
Bibliografía
[1.]
E.S. Knochenhauer, T.J. Key, M. Kahsar-Miller, W. Waggoner, L.R. Boots, R. Azziz.
Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.
J Clin Endocrinol Metab, 83 (1998), pp. 3078-3082
[2.]
E. Diamanti-Kandarakis, C.R. Kouli, A.T. Bergiele, et al.
A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.
J Clin Endocrinol Metab, 84 (1999), pp. 4006-4011
[3.]
M. Asuncion, R.M. Calvo, J.L. San Millán, J. Sancho, S. Ávila, H.F. Escobar-Morreale.
A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.
J Clin Endocrinol Metab, 5 (2000), pp. 2434-2438
[4.]
The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
Fertil Steril, 81 (2004), pp. 19-25
[5.]
A. Dunaif.
Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.
Endocr Rev, 18 (1997), pp. 774-800
[6.]
P. Moghetti, R. Castello.
New routes in the polycystic ovary syndrome labyrinth: a way out?.
J Endocrinol Invest, 21 (1998), pp. 648-655
[7.]
R.A. Lobo, E. Carmina.
The importance of diagnosing the polycystic ovary syndrome.
Ann Intern Med, 132 (2000), pp. 989-993
[8.]
R.S. Legro.
Polycystic ovary syndrome and cardiovascular disesase: a premature association?.
Endocr Rev, 24 (2003), pp. 302-312
[9.]
P.A. Essah, J.E. Nestler.
The metabolic syndrome in polycystic ovary syndrome.
J Endocrinol Invest, 29 (2006), pp. 270-280
[10.]
M.E. Zanolin, F. Tosi, G. Zoppini, et al.
Clustering of cardiovascular risk factors associated with the insulin resistance syndrome: assessment by principal component analysis in young hyperandrogenic women.
Diabetes Care, 29 (2006), pp. 372-378
[11.]
R.L. Barbieri, A. Makris, R.W. Randall, G. Daniels, R.W. Kristner, K.J. Ryan.
Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism.
J Clin Endocrinol Metab, 62 (1986), pp. 904-910
[12.]
P. Moghetti, R. Castello, C. Negri, et al.
Insulin infusion amplifies 17alpha-hydroxycorticosteroid intermediates response to ACTH in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity.
J Clin Endocrinol Metab, 81 (1996), pp. 881-886
[13.]
J.E. Nestler, L.P. Powers, D.W. Matt.
A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome.
J Clin Endocrinol Metab, 72 (1991), pp. 83-89
[14.]
E.Y. Adashi, A.J.W. Hsueh, S.C.C. Yen.
Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells.
Endocrinology, 108 (1981), pp. 1441-1449
[15.]
J.E. Nestler, C.O. Barlascini, D.W. Matt, et al.
Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 68 (1989), pp. 1027-1032
[16.]
G.M. Prelevic, M.I. Wurzburger, L. Balint-Peric, J.S. Nesic.
Inhibitory effect of sandostatin on luteinizing hormone and ovarian steroids in polycystic ovary syndrome.
Lancet, 336 (1990), pp. 900-903
[17.]
A. Gambineri, L. Patton, R. De Iasio, et al.
Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome.
J Clin Endocrinol Metab, 90 (2005), pp. 3854-3862
[18.]
R. Pasquali, D. Antenucci, F. Casimirri, et al.
Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss.
J Clin Endocrinol Metab, 68 (1989), pp. 173-179
[19.]
D.S. Kiddy, D. Hamilton-Fairley, A. Bush, F. Short, V. Anyaoku, M.J. Reed.
Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome.
Clin Endocrinol, 36 (1992), pp. 105-111
[20.]
E. Murphy, J.J. Nolan.
Insulin sensitizer drugs.
Exp Opin Invest Drugs, 9 (2000), pp. 1347-1361
[21.]
J. Lord, I. Flight, R. Norman.
Insulin sensitizing drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.
Cochrane Database Syst Rev, 3 (2003),
[22.]
E.M. Velázquez, S. Mendoza, T. Hamer, F. Sosa, C.J. Glueck.
Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy.
Metabolism, 43 (1994), pp. 647-654
[23.]
J.E. Nestler, D.J. Jakubowicz, W.S. Evans, R. Pasquali.
Effects of metformin on spontaneus and clomiphene-induced ovulation in the polycystic ovary syndrome.
N Engl J Med, 338 (1998), pp. 1876-1880
[24.]
P. Moghetti, R. Castello, C. Negri, et al.
Metformin effects on clinical features, endocrine and metabolic profiles and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.
J Clin Endocrinol Metab, 85 (2000), pp. 139-146
[25.]
R. Azziz, D. Ehrmann, R.S. Legro, et al.
Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, doubleblind, placebo-controlled trial.
J Clin Endocrinol Metab, 86 (2001), pp. 1626-1632
[26.]
S. Palomba, F. Orio Jr., A. Falbo, et al.
Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 90 (2005), pp. 4068-4074
[27.]
R. Fleming, Z.E. Hopkinson, A.M. Wallace, I.A. Greer, N. Sattar.
Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial.
J Clin Endocrinol Metab, 87 (2002), pp. 569-574
[28.]
C.J. Glueck, H. Phillips, D. Cameron, L. Sieve-Smith, P. Wang.
Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first trimester spontaneous abortion: a pilot study.
Fertil Steril, 75 (2001), pp. 45-52
[29.]
D.J. Jakubowicz, M.J. Iurno, S. Jakubowicz, K.A. Roberts, J.E. Nestler.
Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.
J Clin Endocrinol Metab, 87 (2002), pp. 524-529
[30.]
C.J. Kelly, D. Gordon.
The effect of metformin on hirsutism in polycystic ovary syndrome.
Eur J Endocrinol, 147 (2002), pp. 217-221
[31.]
P. Spritzer, L. Bilaud, J.C. Thalabard, et al.
Cyproterone acetate versus hydrocortisone treatment in late onset adrenal hyperplasia.
J Clin Endocrinol Metab, 70 (1990), pp. 642-646
[32.]
C.J. Glueck, R. Papanna, P. Wang, et al.
Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome.
Metabolism, 52 (2003), pp. 908-915
[33.]
R.S. Legro, R. Azziz, D. Ehrmann, A.G. Fereshetian, M. O’Keefe, M.N. Ghazzi.
Minimal response of circulating lipids in women with polycystic ovary syndrome to improvement in insulin sensitivity with troglitazone.
J Clin Endocrinol Metab, 88 (2003), pp. 5137-5144
[34.]
E. Diamanti-Kandarakis, G. Spina, C. Kouli, et al.
Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy.
J Clin Endocrinolol Metab, 86 (2001), pp. 4666-4673
[35.]
G. Paradisi, H.O. Steinberg, M.K. Shepard, et al.
Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 88 (2003), pp. 576-580
[36.]
L. Morin-Papunen, K. Rautio, A. Ruokonen, et al.
Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 88 (2003), pp. 4649-4654
[37.]
F Orio Jr, S. Palomba, T. Cascella, et al.
Improvement in endothelial structure and function after metformin treatment in young normalweight women with polycystic ovary syndrome: results of a 6-month study.
J Clin Endocrinol Metab, 90 (2005), pp. 6072-6076
[38.]
J.C. Crave, S. Fimbel, H. Lejeune, N. Cugnardey, H. Dechaud, M. Pugeat.
Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women.
J Clin Endocrinol Metab, 80 (1995), pp. 2057-2062
[39.]
R. Pasquali, D. Gambineri, D. Biscotti, et al.
Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.
J Clin Endocrinol Metab, 85 (2000), pp. 2767-2774
[40.]
D.J. Jakubovicz, J.E. Nestler.
Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17a activity and serum androgens.
J Clin Endocrinol Metab, 82 (1997), pp. 4075-4079
[41.]
J.P. Baillargeon, D.J. Jakubowicz, M.J. Iuorno, S. Jakubowicz, J.E. Nestler.
Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.
Fertil Steril, 82 (2004), pp. 893-902
[42.]
J.E. Nestler.
Metformin and the polycystic ovary syndrome.
J Clin Endocrinol Metab, 86 (2001), pp. 1430
[43.]
L.R. Harborne, N. Sattar, J.E. Norman, R. Fleming.
Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses.
J Clin Endocrinol Metab, 90 (2005), pp. 4593-4598
[44.]
R.S. Rittmaster.
Medical treatment of androgen-dependent hirsutism.
J Clin Endocrinol Metab, 80 (1995), pp. 2559-2563
[45.]
P. Moghetti, V. Toscano.
Treatment of hirsutism and acne in hyperandrogenism.
Best practice and research: clinical endocrinology and metabolism Polycystic ovary syndrome and hyperandrogenism, pp. 221-234
[46.]
P. Moghetti, F. Tosi, A. Tosti, et al.
Comparison of spironolactone, flutamide and finasteride efficacy in the treatment of hirsutism: a randomized, double-blind, placebo-controlled trial.
J Clin Endocrinol Metab, 85 (2000), pp. 89-94
[47.]
D.K. Wysowski, J.P. Freiman, J.B. Tourtelot, M.L. Horton.
Fatal and nonfatal hepatotoxicity associated with flutamide.
Ann Intern Med, 118 (1993), pp. 860-864
[48.]
J.R. Givens, R.N. Andersen, W.L. Wiser, A.J. Donelson, S.A. Coleman.
A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease.
J Clin Endocrinol Metab, 41 (1975), pp. 845-853
[49.]
D. Dewailly, M.C. Vantyghem-Haudiquet, C. Sainsard, et al.
Clinical and biological phenotypes in late-onset 21-hydroxylase deficiency.
J Clin Endocrinol Metab, 63 (1986), pp. 418-423
[50.]
D.H. Abbott, D.A. Dumesic, J.R. Eisner, J.W. Kenmitz, R.W. Goy.
The prenatally androgenized female rhesus monkey as a model for PCOS.
Androgen excess disorders in women, pp. 369-382
[51.]
R. Homburg, A. Amsterdam.
Polycystic ovary syndrome. Loss of the apoptotic mechanism in the ovarian follicles?.
J Endocrinol Invest, 21 (1998), pp. 552-557
[52.]
C.A. Eagleson, M.B. Gingrich, C.L. Pastor, et al.
Polycystic ovary syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone.
J Clin Endocrinol Metab, 85 (2000), pp. 4047-4052
[53.]
K.H. Polderman, L.J.G. Gooren, H. Asscheman, et al.
Induction of insulin resistance by androgens and estrogens.
J Clin Endocrinol Metab, 79 (1994), pp. 265-271
[54.]
A. Holmang, J. Svedberg, E. Jennische, P. Bjorntorp.
Effects of testosterone on muscle insulin sensitivity and morphology in female rats.
Am J Physiol, 259 (1990), pp. E555-E560
[55.]
F. Moghetti, R. Tosi, R. Castello, et al.
The insulin resistance in women with hyperandrogenism is partially reversed by anti-androgen treatment: evidence that androgens impair insulin action in women.
J Clin Endocrinol Metab, 81 (1996), pp. 952-960
[56.]
R. Pasquali.
Obesity and androgens: facts and perspectives.
Fertil Steril, 85 (2006), pp. 1319-1340
[57.]
J. Holte, T. Bergh, C. Berne, L. Wide, H. Lithell.
Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 80 (1995), pp. 2586-2593
[58.]
L. Ibáñez, C. Valls, S. Cabre, F. De Zegher.
Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperandrogenism: the key role of early, low-dose flutamide.
J Clin Endocrinol Metab, 89 (2004), pp. 4716-4720
[59.]
A. Gambineri, C. Pelusi, S. Genghini, et al.
Effect of metformin and flutamide administered alone or in combination in dieting obese women with polycystic ovary syndrome.
Clin Endocrinol, 60 (2004), pp. 241-249
[60.]
E. Diamanti-Kandarakis, A. Mitrakou, S. Raptis, G. Tolis, A.J. Duleba.
The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome.
J Clin Endocrinol Metab, 83 (1998), pp. 2699-2705
[61.]
L. Ibáñez, N. Potau, M.V. Marcos, F. De Zegher.
Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide.
J Clin Endocrinol Metab, 85 (2000), pp. 3251-3255
[62.]
V. De Leo, D. Lanzetta, D. D’Antona, A. La Marca, G. Morgante.
Hormonal effects of flutamide in young women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 83 (1998), pp. 99-102
[63.]
P. Falasca, M. Poggi, A. Stigliano, S. Monti, F. Sciarra, V. Toscano.
Flutamide effects on hirsutism, acne, menstrual cyclicity and ovulation restoration.
Proc. 83rd Annual Meeting of the Endocrine Society,
Copyright © 2006. Sociedad Española de Endocrinología y Nutrición
