Semin Reprod Med 2003; 21(3): 277-284
DOI: 10.1055/s-2003-43305
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Pharmacologic Treatment of Polycystic Ovary Syndrome

David A. Ehrmann1 , Daniel Rychlik2
  • 1Department of Medicine, Section of Endocrinology, The University of Chicago, Chicago, Illinois
  • 2Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, The University of Chicago, Chicago, Illinois
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
31. Oktober 2003 (online)

ABSTRACT

Women with polycystic ovary syndrome (PCOS) most often seek treatment for reduction of hair growth and/or acne, restoration of menstrual cyclicity, and infertility. In addition, these patients are increasingly seeking advise and treatment for the metabolic abnormalities related to PCOS (e.g., insulin resistance and type 2 diabetes). In this review, we outline the pathophysiologic events underlying the cutaneous manifestations of androgen excess and provide a rationale for use of the various pharmacologic agents available for treatment. Options for the treatment of the reproductive abnormalities (menstrual dysfunction and interfility) are presented. Finally, the metabolic manifestations of PCOS are reviewed and their treatment is discussed.

REFERENCES

  • 1 Kuhl H. Comparative pharmacology of newer progestogens.  Drugs . 1996;  51 188-215
  • 2 Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen.  Contraception . 2000;  62 29-38
  • 3 Mowszowicz I, Wright F, Vincens M. Androgen metabolism in hirsute patients treated with cyproterone acetate.  J Steroid Biochem . 1984;  20 757-761
  • 4 Miller J, Jacobs H. Treatment of hirsutism and acne with cyproterone acetate.  Clin Endocrinol Metab . 1986;  15 373-389
  • 5 Miller J, Wojnarowska F, Dowd P. Antiandrogen treatment in women with acne: a controlled trial.  Br J Dermatol . 1986;  114 705-716
  • 6 Barth J, Cherry C, Wojnarowska F, Dawber R. Spironolactone is an effective and well tolerated systemic antiandrogen therapy for hirsute women.  J Clin Endocrinol Metab . 1989;  68 966-970
  • 7 O'Brien R, Cooper M, Murray R. Comparison of sequential cyproterone acetate versus spironolactone/oral contraceptive in the treatment of hirsutism.  J Clin Endocrinol Metab . 1991;  72 1008-1013
  • 8 Crosby P, Rittmaster R. Predictors of clinical response in hirsute women treated with spironolactone.  Fertil Steril . 1991;  55 1076-1081
  • 9 Givens J. Treatment of hirsutism with spironolactone.  Fertil Steril . 1985;  43 841-843
  • 10 Neri R, Monahan M. Effects of a novel nonsteroidal antiandrogen on canine prostatic hyperplasia.  Invest Urol . 1972;  10 123-130
  • 11 Cusan L, Dupont A, Belanger A, Tremblay R, Manhes G, Labrie F. Treatment of hirsutism with the pure antiandrogen flutamide.  J Am Acad Dermatol . 1990;  23 462-469
  • 12 Pazos F, Escobar-Morreale H F, Balsa J, Sancho J M, Varela C. Prospective randomized study comparing the long-acting gonadotropin-releasing hormone agonist triptorelin, flutamide, and cyproterone acetate, used in combination with an oral contraceptive, in the treatment of hirsutism.  Fertil Steril . 1999;  71 122-128
  • 13 Rittmaster R. Differential suppression of testosterone and estradiol in hirsute women with the superactive gonadotropin-releasing hormone agonist leuprolide.  J Clin Endocrinol Metab . 1988;  67 651-655
  • 14 Sidenius-Johansen J, Juel-Riis B, Hassager C, Moen M, Jacobson J, Christiansen C. The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism.  J Clin Endocrinol Metab . 1988;  67 701-706
  • 15 Matta W, Shaw R, Hesp R, Evans R. Reversible trabecular bone density loss following induced hypooestrogenism with the GnRH analogue buserelin in premenopausal women.  Clin Endocrinol (Oxf) . 1988;  29 45-51
  • 16 Adashi E. Potential utility of gonadotropin-releasing hormone agonists in the management of ovarian hyperandrogenism.  Fertil Steril . 1990;  53 765-779
  • 17 Rittmaster R, Loriaux D, Cutler G. Sensitivity of cortisol and adrenal androgens to dexamethasone suppression in hirsute women.  J Clin Endocrinol Metab . 1985;  61 462-466
  • 18 Steinberger E, Rodriguez-Rigau L, Weidman E, Smith K, Ayala C. Glucocorticoid therapy in hyperandrogenism.  Baillieres Clin Obstet Gynaecol . 1990;  4 457-471
  • 19 Azziz R, Rafi A, Smith B R, Bradley Jr L E, Zacur H A. On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.  J Clin Endocrinol Metab . 1990;  70 431-436
  • 20 Liang T, Rasmusson G, Brooks J. Biochemical and biological studies with 4-aza-steroidal 5α-reductase inhibitors.  J Steroid Biochem . 1983;  19 385-390
  • 21 Rittmaster R S. 5alpha-Reductase inhibitors.  J Androl . 1997;  18 582-587
  • 22 Jafari K, Tavaheri C, Ruiz G. Endometrial adenocarcinoma and the Stein-Leventhal syndrome.  Obstet Gynecol . 1978;  51 97-100
  • 23 Coulam C, Annegers J, Kranz J. Chronic anovulation syndrome and associated neoplasia.  Obstet Gynecol . 1983;  61 403-407
  • 24 Farhi D, Nosanchuk J, Silverberg S. Endometrial adenocarcinoma in women under 25 years of age.  Obstet Gynecol . 1986;  68 741-745
  • 25 Bayer S, DeCherney A. Clinical manifestations and treatment of dysfunctional uterine bleeding.  JAMA . 1993;  269 1823-1828
  • 26 Group P TW. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women.  JAMA . 1995;  273 199-208
  • 27 Woodruff J, Pickar J. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone.  Am J Obstet Gynecol . 1994;  170 1213-1223
  • 28 Messinis I, Milingos S. Current and future status of ovulation induction in polycystic ovary syndrome.  Hum Reprod Update . 1997;  3 235-253
  • 29 Barnes R. Diagnosis and therapy of hyperandrogenism.  Baillieres Clin Obstet Gynaecol . 1997;  11 369-396
  • 30 Hammond M, Halme J, Talbert L. Factors affecting the pregnancy rate in clomiphene citrate induction of ovulation.  Obstet Gynecol . 1983;  62 196-202
  • 31 Gysler M, March C, Mishell D, Bailey E. A decade's experience with an individualized clomiphene treatment regimen including its effects on the post-coital test.  Fertil Steril . 1982;  37 161-167
  • 32 Glueck C J, Phillips H, Cameron D, Sieve-Smith L, Wang P. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study.  Fertil Steril . 2001;  75 46-52
  • 33 Sagle A, Hamilton-Fairley D, Kiddy D, Franks S. A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome.  Fertil Steril . 1991;  55 56-60
  • 34 Buvat J, Buvat-Herbaut M, Marcolin G. Purified follicle-stimulating hormone in polycystic ovary syndrome: slow administration is safer and more effective.  Fertil Steril . 1989;  52 553-559
  • 35 Shoham Z, Patel A, Jacobs H. Polycystic ovarian syndrome: safety and effectiveness of stepwise and low-dose administration of purified follicle-stimulating hormone.  Fertil Steril . 1991;  55 1051-1056
  • 36 Mizunuma H, Takagi T, Yamada K. Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome.  Fertil Steril . 1991;  55 1195-1196
  • 37 Homburg R, Levy T, Ben-Rafael Z. A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome.  Fertil Steril . 1995;  63 729-733
  • 38 Brzyski R, Grow D, Sims J, Seltman H. Increase in androgen:estrogen ratio specifically during low-dose follicle-stimulating hormone therapy for polycystic ovary syndrome.  Fertil Steril . 1995;  64 693-697
  • 39 Hugues J, Cedrin-Durnerin I, Avril C. Sequential step-up and step-down regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome.  Hum Reprod . 1996;  11 2581-2584
  • 40 van Santbrink E, Fauser B. Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: prospective, randomized comparison between low dose step-up and step-down dose regimens.  J Clin Endocrinol Metab . 1997;  82 3597-3602
  • 41 White D, Polson D, Kiddy D. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women.  J Clin Endocrinol Metab . 1996;  81 3821-3824
  • 42 Homburg R, Levy T, Berkovitz D. Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome.  Fertil Steril . 1993;  59 527-531
  • 43 Balen A, Tan S, MacDougall J, Jacobs H. Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin.  Hum Reprod . 1993;  8 959-964
  • 44 Campo S. Ovulatory cycles, pregnancy outcome and complications after surgical treatment of polycystic ovary syndrome.  Obstet Gynecol Surv . 1998;  53 297-308
  • 45 Amar N, Lachelin G. Laparoscopic ovarian diathermy: an effective treatment for anti-oestrogen resistant anovulatory infertility in women with the polycystic ovary syndrome.  Br J Obstet Gynaecol . 1993;  100 161-164
  • 46 Donesky B, Adashi E. Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy.  Fertil Steril . 1995;  63 439-463
  • 47 Kiddy D S, Hamilton-Fairley D, Bush A. et al . Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome.  Clin Endocrinol (Oxf) . 1992;  36 105-111
  • 48 Velazquez E M, Mendoza S G, Wang P, Glueck C J. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome.  Metabolism . 1997;  46 454-457
  • 49 Hasegawa I, Murakawa H, Suzuki M. Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome.  Fertil Steril . 1999;  71 323-327
  • 50 Azziz R, Ehrmann D, Legro R S. et al . Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial.  J Clin Endocrinol Metab . 2001;  86 1626-1632
  • 51 Nestler J, Jakubowicz D, Evans W, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.  N Engl J Med . 1998;  338 1876-1880
  • 52 Inzucchi S E, Maggs D G, Spollett G R. et al . Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus.  N Engl J Med . 1998;  338 867-872
  • 53 Ehrmann D, Cavaghan M, Imperial J, Sturis J, Rosenfield R, Polonsky K. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome.  J Clin Endocrinol Metab . 1997;  82 524-530
  • 54 Nestler J E, Jakubowicz D J. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.  N Engl J Med . 1996;  335 617-623
  • 55 Nestler J E, Stovall D, Akhter N, Iuorno M J, Jakubowicz D J. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome.  Fertil Steril . 2002;  77 209-215
  • 56 Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.  J Clin Endocrinol Metab . 1996;  81 3299-3306
  • 57 Ehrmann D, Schneider D, Sobel B. et al . Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome.  J Clin Endocrinol Metab . 1997;  82 2108-2116
    >