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Management of Hirsutism

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Abstract

This review reports our own experience with, and literature studies of, the pharmacological management of hirsutism in women with hyperandrogenism (polycystic ovary syndrome) or with normal serum androgen levels and regular ovulatory menstrual cycles (idiopathic hirsutism). Treatment consists of suppressing ovarian or adrenal androgen secretion, or blocking androgen actions in the skin. The major drugs used are gonadotropinreleasing hormone (GnRH) agonists, combined oral contraceptives (COCs), and steroidal (cyproterone acetate and spironolactone) or nonsteroidal (flutamide and finasteride) antiandrogens.

GnRH agonists, suppressing the pituitary, decrease androgen and estradiol secretion and improve severe hirsutism. To avoid estrogen deficiency problems, ‘add back’ therapy with estrogen-progestogen or COCs is advisable. This method of treatment is complicated and expensive, limiting its use to severe forms of ovarian hyperandrogenism with hyperinsulinemia.

The third-generation COCs, containing new progestogens or cyproterone, have very restricted effectiveness in the short term (6 cycles), but their long term use (>12 cycles) cures mild-to-moderate hirsutism and improves severe hirsutism. As well as suppressing gonadotropins and ovarian androgen steroidogenesis, these formulations decrease free testosterone levels and may also decrease adrenal androgen production. In women being treated with antiandrogens, COCs are important to provide control of the menstrual cycle and contraception.

Cyproterone, a progestational agent, inhibits gonadotropin secretion and blocks androgen action. It is used in COCs or in a reverse sequential regimen. In the latter, it is very effective in the short term treatment of hirsutism.

Spironolactone blocks androgen receptors. Its effectiveness in hirsutism is dosage-dependent: low dosages are less active than other antiandrogens, whereas high dosages (200 mg/day) are very effective at the cost of several adverse effects (particularly dysfunctional uterine bleeding), but the concomitant use of a COC may prevent these.

Flutamide is a pure antiandrogen that blocks androgen receptors and inhibits hair growth. It is very effective in treating hirsutism within 6 to 12 months. Dry skin is very frequent during treatment with flutamide, and hepatotoxicity is possible at high dosages. Finasteride, a 5α-reductase type 2 inhibitor, is the least effective antiandrogen, but a dosage of 5 mg/day decreases hirsutism without adverse effects. Pregnancy must be avoided during therapy with antiandrogens because of the possible risk of abnormal development of a male fetus.

Antiandrogens, especially flutamide (250 to 500 mg/day) and cyproterone (12.5 to 50 mg/day in a reverse sequential regimen), alone or in association with COCs, seem to be the most effective agents for the treatment of hirsutism.

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References

  1. Knochenhauer E.S., Azziz R. Advances in the diagnosis and treatment of the hirsute patient. Curr Opin Obstet Gynecol 1995; 7: 344–350

    Article  PubMed  CAS  Google Scholar 

  2. Azziz R., Ochoa T. Idiopathic hirsutism (IH): an uncommon cause of hirsutism in Alabama [abstract P 075]. 53rd Annual Meeting of the American Society of Reproductive Medicine; 1997 Oct 18–22; Cincinnati

    Google Scholar 

  3. Carmina E.Prevalence of idiophatic hirsutism. Eur J Endocrinol 1998; 139: 421–423

    Article  PubMed  CAS  Google Scholar 

  4. Maroulis G.B. Evaluation of hirsutism and hyperandrogenemia. Fertil Steril 1981; 36: 273–305

    PubMed  CAS  Google Scholar 

  5. Rittmaster R.S., Loriaux D.L. Hirsutism. Ann Intern Med 1987; 106: 95–107

    PubMed  CAS  Google Scholar 

  6. Serafini P., Lobo R.A. Increased 5-alpha reductase activity in idiopathic hirsutism.Fertil Steril 1985; 43: 74–78

    PubMed  CAS  Google Scholar 

  7. Barbieri R.L. Polycystic ovarian disease. Annu Rev Med 1991; 42: 199–204

    Article  PubMed  CAS  Google Scholar 

  8. Ehrman D.A., Barnes R.B., Rosenfield R.L. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion.Endocrinol Rev 1995; 16: 322–353

    Google Scholar 

  9. Goldzieher J.W., Green J.A. The polycystic ovary: clinical and histologic features.J Clin Endocrinol Metab 1962; 22: 325–338

    Article  PubMed  CAS  Google Scholar 

  10. Conway G.S., Honour J.W., Jacobs H.S. Heterogeneity of the polycystic ovary syndrome: clinical, endocrine and ultrasound features in 556 patients. Clin Endocrinol 1989; 30: 459–470

    Article  CAS  Google Scholar 

  11. Prevelic G. Insulin resistance in polycystic ovary syndrome. Curr Opin Obstet Gynecol1997; 9: 193–201

    Google Scholar 

  12. Acièn P., Quereda F., Matallìn P., et al. Insulin, androgens and obesity in women with and without polycystic ovary syndrome: a heterogeneous group of disorders.Fertil Steril 1999; 72: 32–40

    Article  PubMed  Google Scholar 

  13. Falsetti L., Eleftheriou G. Hyperinsulinemia in the polycystic ovary syndrome: a clinical, endocrine and echographic study in 240 patients. Gynecol Endocrinol 1996; 10: 319–326

    Article  PubMed  CAS  Google Scholar 

  14. Duleba A.J., Spaczynski R.Z., Olive D.L. Insulin and insulin-like growth factor I stimulate the proliferation of human ovarian theca-interstitial cells. Fertil Steril 1998; 69: 335–340

    Article  PubMed  CAS  Google Scholar 

  15. Paulson R.J., Serafini P.C., Catalino J.A., et al. Measurements of 3α,17β-androstanediol glucuronide in serum and urine and the correlation with skin 5α-reductase activity. Fertil Steril 1986; 46: 222–226

    PubMed  CAS  Google Scholar 

  16. Falsetti L., Rosina B., De Fusco D. Serum levels of 3α-androstanediol glucuronide in hirsute and non hirsute women. Eur J Endocrinol 1998; 138: 385–389

    Article  Google Scholar 

  17. Jahanfar S., Eden J.A., Warren P., et al. A twin study of polycystic ovary syndrome.Fertil Steril 1995; 63: 478–486

    PubMed  CAS  Google Scholar 

  18. George F.W., Russel D.W., Wilson J.D. Feed-forward control of prostatic growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5α-reductase. Proc Natl Acad Sci USA 1991; 88: 8044–8047

    Article  PubMed  CAS  Google Scholar 

  19. Lobo R.A. Hirsutism in polycystic ovary syndrome: current concepts. Clin Obstet Gynecol 1991; 34: 817–825

    Article  PubMed  CAS  Google Scholar 

  20. Lobo R.A., Kletzky O.A. Normalization of androgen and sex hormone binding globulin levels after treatment of hyperprolactinemia. J Clin Endocrinol Metab1983; 56: 562–568

    Article  CAS  Google Scholar 

  21. Danilenko D.M., Ring B.D., Pierce G.F. Growth factors and cytokines in hair follicle development and cycling: recent insights from animal models and the potentials for clinical therapy. Mol Med Today 1996; 2: 460–467

    Article  PubMed  CAS  Google Scholar 

  22. Andersson S., Bishop R.W. & Russell D.W. Expression, cloning and regulation of the steroid 5α-reductase, an enzyme essential for male sexual differentiation.J Biol Chem 1989; 264: 16249–16255

    PubMed  CAS  Google Scholar 

  23. Andersson S., Berman D.M., Jenkins E.P., et al. Deletione of the steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature 1991; 354: 159–161

    Article  PubMed  CAS  Google Scholar 

  24. Mestayer C.H., Berthaut I., Portois M.C., et al. Predominant expression of 5α-reductase type 1 in pubic skin from normal subjects and hirsute patients. J Clin Endocrinol Metab 1996; 81: 1989–1993

    Article  PubMed  CAS  Google Scholar 

  25. Roger S., Rittmaster M.D. Finasteride. N Engl J Med 1994; 330: 120–125

    Article  Google Scholar 

  26. Harris G., Azzolina B., Baginsky W., et al. Identification and selective inhibition of an isozyme of steroid 5α-reductase in human scalp. Proc Natl Acad Sci USA1992; 89: 10787–10791

    Article  CAS  Google Scholar 

  27. Moore R.J., Wilson J.D. Steroid 5α-reductase in cultured human fibroblasts: biochemical and genetic evidence for two distinct enzyme activities. J Biol Chem 1976; 251: 5895–5900

    PubMed  CAS  Google Scholar 

  28. Paus R., Cotsarelis G. The biology of hair follicles. N Engl J Med 1999; 341: 491–497

    Article  PubMed  CAS  Google Scholar 

  29. Adams J., Polson D.W., Abdulwahid N., et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone.Lancet 1985; 2: 1375–1378

    Article  PubMed  CAS  Google Scholar 

  30. Ferriman D., Gallwey J.D. Clinical assessment of body hair growth in woman. J Clin Endocrinol Metab 1961; 21: 1440–1448

    Article  PubMed  CAS  Google Scholar 

  31. Chang R.J., Laufer R.L., Meldrum D.R., et al. Steroid secretion in polycystic ovarian desease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist. J Clin Endocrinol Metab 1983; 56: 897–904

    Article  PubMed  CAS  Google Scholar 

  32. Wilson E.E., Little B.B., Byrd W., et al. The effect of gonadotropin-releasing hormone agonists on adrenocorticotropin and cortisol secretion in premenopausal women.J Clin Endocrinol Metab 1993; 76: 162–169

    Article  PubMed  CAS  Google Scholar 

  33. Falsetti L., Pasinetti E. Treatment of moderate and severe hirsutism by gonadotropin-releasing hormone agonists in women with polycystic ovary syndrome and idiopathic hirsutism. Fertil Steril 1994; 61: 817–822

    PubMed  CAS  Google Scholar 

  34. Cagnacci A., Paoletti A.M., Arangino S., et al. Effect of ovarian suppression on glucose metabolism of young lean women with or without ovarian hyperandrogenism.Hum Reprod 1999; 14: 893–897

    Article  PubMed  CAS  Google Scholar 

  35. Morcos R.M., Abdul-Malak M.E., Shikora E. Treatment of hirsutism with gonadotropin-releasing hormone agonist and estrogen replacement therapy. Fertil Steril 1994; 61: 427–431

    PubMed  CAS  Google Scholar 

  36. Carmina E., Janni A., Lobo R.A. Physiological estrogen replacement may enance the effectiveness of the gonadotropin-releasing hormone agonist in the treatment of hirsutism. J Clin Endocrinol Metab 1994; 78: 126–130

    Article  PubMed  CAS  Google Scholar 

  37. Heiner J.S., Greendale G.A., Kawakami A.K., et al. Comparison of gonadotropin-releasing hormone agonist and low dose oral contraceptive given alone or together in the treatment of hirsutism. J Clin Endocrinol Metab 1995; 80: 3412–3418

    Article  PubMed  CAS  Google Scholar 

  38. Andreyko J.L., Monroe S.E., Jaffe R.B. Treatment of hirsutism with gonadotropin-releasing hormone agonist (Naferelin). J Clin Endocrinol Metab 1986; 63: 854–859

    Article  PubMed  CAS  Google Scholar 

  39. Suikkari A.M., Tiitinen A., Stenman U.H., et al. Oral contraceptives increase IGFBP-1 in women with polycystic ovarian disease. Fertil Steril 1991; 55: 895–899

    PubMed  CAS  Google Scholar 

  40. Porcile A., Gallardo E. Long-term treatment of hirsutism: desogestrel compared with cyproterone acetate in oral contraceptives. Fertil Steril 1991; 55: 877–881

    PubMed  CAS  Google Scholar 

  41. Falsetti L., Ramazzotto F., Rosina B. Efficacy of combined ethinyloestradiol (0.035 mg) and cyproterone acetate (2 mg) in acne and hirsutism in women with polycystic ovary syndrome. J Obstet Gynecol 1997; 17: 565–568

    Article  CAS  Google Scholar 

  42. Falsetti L., Galbignani E. Long-term treatment with the combination ethinylestradiol and cyproterone acetate in polycystic ovary syndrome. Contraception 1990; 42: 611–619

    Article  PubMed  CAS  Google Scholar 

  43. Brogden R.N., Clissold S.P. Flutamide: a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in advanced prostatic cancer. Drugs 1989; 38: 185–203

    Article  PubMed  CAS  Google Scholar 

  44. Pucci E., Genazzani A.D., Monzani F., et al. Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome. Gynecol Endocrinol 1995; 9: 221–228

    Article  PubMed  CAS  Google Scholar 

  45. Couzinet B., Pholsena M., Young J., et al. The impact of a pure anti-androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism. Clin Endocrinol 1993; 39: 157–162

    Article  CAS  Google Scholar 

  46. Moghetti P., Castello R., Negri C. et al. Flutamide in the treatment of hirsutism: Long-term clinical effects, endocrine changes and androgen receptor behaviour.Fertil Steril 1995; 64: 511–517

    PubMed  CAS  Google Scholar 

  47. Calandra R.S., Purvis K., Naess O., et al. Androgen receptors in the rat adrenal gland.J Steroid Biochem Mol Biol 1978; 9: 1009–1015

    CAS  Google Scholar 

  48. Bèlanger A., Labrie F., Dupont A., et al. Endocrine effects of combined treatment with an LHRH-agonist in association with flutamide in metastatic prostatic carcinoma.Clin Invest Med 1988; 11: 321–326

    PubMed  Google Scholar 

  49. Falsetti L., Gambera A. Comparison of finasteride and flutamide in the treatment of idiopathic hirsutism. Fertil Steril 1999; 72: 41–46

    Article  PubMed  CAS  Google Scholar 

  50. Cusan L., Dupont A., Belanger A., et al. Treatment of hirsutism with the pure antiandrogen flutamide. J Ann Acad Dermatol 1990; 23: 462–469

    Article  CAS  Google Scholar 

  51. De Leo V., Lanzetta D., D’Antona D., et al. Hormonal effects of flutamide in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83: 99–102

    Article  PubMed  Google Scholar 

  52. Venturoli S., Marescalchi O., Colombo F.M., et al. A prospective randomized trial comparing low dose flutamide, finasteride, ketoconazole and cyproterone acetate-estrogen regimens in the treatment of hirsutism. J Clin Endocrinol Metab1999; 84: 1304–1310

    Article  CAS  Google Scholar 

  53. Erenus M., Gübürz O., Durmusoglu F., et al. Comparison of the efficacy of spironolactone versus flutamide in the treatment of hirsutism. Feril Steril 1994; 61: 613–616

    CAS  Google Scholar 

  54. Falsetti L., Gambera A., Legrenzi L., et al. Comparison of finasteride versus flutamide in the treatment of hirsutism. Eur J Endocrinol 1999; 141: 361–367

    Article  PubMed  CAS  Google Scholar 

  55. Falsetti L., De Fusco D., Eleftheriou G., et al. Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome. Gynecol Endocrinol 1997; 11: 251–257

    Article  PubMed  CAS  Google Scholar 

  56. Crownover R.L., Holland J., Chen A., et al. Flutamide induced liver toxicity including fatal hepatic necrosis. Int J Radiat Oncol Biol Phys 1996; 34: 911–915

    Article  PubMed  CAS  Google Scholar 

  57. Moszowitcz I., Wright F., Vicens M., et al. Androgen metabolism in hirsute patients treated with cyproterone acetate. Steroid Biochem 1986; 20: 757–761

    Article  Google Scholar 

  58. Marcondes J.A., Waychenberg B.L., Abujamra A.G., et al. Monthly cyproterone acetate in the treatment of hirsute women: clinical and laboratory effects. Fertil Steril 1990; 53: 40–44

    PubMed  CAS  Google Scholar 

  59. Fruzetti F., Bersi C., Parrini D., et al. Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects. Fertil Steril 1999; 71: 445–451

    Article  Google Scholar 

  60. Grigoriou O., Papadias C., Konidaris S., et al. Comparison of flutamide and cyproterone acetate in the treatment of hirsutism: a randomized controlled trial. Gynecol Endocrinol 1996; 10: 119–123

    Article  PubMed  CAS  Google Scholar 

  61. Jasonni B., Bulletti C., Nardi S., et al. Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17ß-estradiol. Fertil Steril 1991; 55: 742–745

    PubMed  CAS  Google Scholar 

  62. Fruzzetti F. Treatment of hirsutism: antiandrogen and 5α-R inhibitor therapy. In: Azziz R., Nestler J.E., Dewnilly D., editors. Androgen excess disorders in women. Philadelphia: Lippincot-Raven, 1997: 787–797

    Google Scholar 

  63. Carmina E., Lobo A.R. Peripheral androgen blockade versus glandular androgen suppression in the treatment of hirsutism. Obstet Gynecol 1991; 78: 845–849

    PubMed  CAS  Google Scholar 

  64. Cumming D.C., Yang J.C., Rebar R.W., et al. Treatment of hirsutism with spironolactone. JAMA 1982; 247: 1295–1305

    Article  PubMed  CAS  Google Scholar 

  65. Barth J.H., Cherry C.A., Wojnarowska F., et al. Spironolactone is an effective and well tolerated systemic antiandrogen therapy for hirsute women. J Clin Endocrinol Metab 1989; 68: 966–970

    Article  PubMed  CAS  Google Scholar 

  66. Dallob A.L., Sadick N.S., Unger W., et al. The effect of finasteride, a 5α-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. J Clin Endocrinol Metab 1994; 79: 703–706

    Article  PubMed  CAS  Google Scholar 

  67. Wong I.L., Morris R.S., Chang L., et al. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 1995; 80: 233–238

    Article  PubMed  CAS  Google Scholar 

  68. Tolino A., Petrone A., Sarnacchiaro F., et al. Finasteride in the treatment of hirsutism: new therapeutic perspectives. Fertil Steril 1996; 66: 61–65

    PubMed  CAS  Google Scholar 

  69. Erenus M., Yücelten D, Durmusoglu F., et al. Comparison of finasteride versus spironolactone in the treatment of idiopathic hirsutism. Feril Steril 1997; 68: 1000–1003

    Article  CAS  Google Scholar 

  70. Castello R., Tosi F., Perrone F., et al. Outcome of long-term treatment with the 5-alpha reductase inhibitor finasteride in idiopathic hirsutism. Clinical and hormonal effects during a 1 year course of therapy and 1 year follow up. Feril Steril 1996; 66: 734–740

    CAS  Google Scholar 

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Falsetti, L., Gambera, A., Platto, C. et al. Management of Hirsutism. Am J Clin Dermatol 1, 89–99 (2000). https://doi.org/10.2165/00128071-200001020-00003

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