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A Risk-Benefit Assessment of Pharmacological Therapies for Hirsutism

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Abstract

In recent years, many new therapeutic regimens for hirsutism have been introduced. This has considerably enlarged the different choices of the physician but at the same time has produced considerable confusion and uncertainty as to what is the best possible therapy for the single patient or for the different pathologies of this condition.

This review presents data on the characteristics, adverse effects and effective dosage for the more commonly used drugs for hirsutism.

In most patients, low doses of antiandrogens (cyproterone acetate, flutamide or spironolactone) are used with few adverse effects and good results in terms of improvement of the hirsutism. Patients with severe hyperandrogenic hirsutism may require larger doses of antiandrogens. In only a few patients, therapy with agents that primarily reduce androgen secretion (mostly a gonadotropin releasing hormone agonist) is needed. In responsive patients, dexamethasone may be used at low doses (associated with an antiandrogen) to prolong the length of the remission. Finally, agents that inhibit 5α-reductase activity (finasteride) may be used as alternative to low dose antiandrogen therapy but the results are often less satisfactory.

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References

  1. Carmina E, Lobo RA. Hirsutism, alopecia and acne. In: Beckers KL, editor. Principles and practice of endocrinology and metabolism. 2nd ed., Philadelphia (PA): Lippincott Publishing, 1995: Part VII: 75–9

    Google Scholar 

  2. de Oliveira RFC, Novaes LP, Lima MB, et al. A new treatment for hirsutism. Ann Intern Med 1975; 83: 817–9

    Google Scholar 

  3. Shapiro G, Evron S. A novel use of spironolactone: treatment of hirsutism. J Clin Endocrinol Metab 1980; 51: 429–32

    Article  PubMed  CAS  Google Scholar 

  4. Cumming DC, Yang JC, Rebar RW, et al. Treatment of hirsutism with spironolactone. JAMA 1982; 247: 1295–8

    Article  PubMed  CAS  Google Scholar 

  5. Helfer EL, Miller JL, Rose LI. Side effects of spironolactone therapy in the hirsute women. J Clin Endocrinol Metab 1988; 66: 208–11

    Article  PubMed  CAS  Google Scholar 

  6. Barth JH, Cherry CA, Wojnarowska F, et al. Spironolactone is an effective and well tolerated systemic antiandrogen therapy for hirsute women. J Clin Endocrinol Metab 1989; 68: 966–70

    Article  PubMed  CAS  Google Scholar 

  7. Loriaux DL, Menard R, Taylor A, et al. Spironolactone and endocrine dysfunction. Ann Intern Med 1976; 85: 630–6

    CAS  Google Scholar 

  8. Serafini PC, Catalino J, Lobo RA. The effect of spironolactone on genital skin 5-reductase activity. J Steroid Biochem 1985; 23: 1911–4

    Article  Google Scholar 

  9. Searafini P, Lobo RA. The effects of spironolactone on adrenal steroidogenesis in hirsute women. Fertil Steril 1985; 44: 595–9

    Google Scholar 

  10. Lobo RA, Shoupe D, Serafini P, et al. The effect of two does of spironolactone on serum androgens and anagen hair in hirsute women. Fertil Steril 1985; 43: 200–5

    PubMed  CAS  Google Scholar 

  11. Carmina E, Lobo RA. Peripheral androgen blockade versus glandular androgen suppression in the treatment of hirsutism. Obstet Gynecol 1991; 18: 845–9

    Google Scholar 

  12. Chapman MG, Dowsett M, Dewhurst CJ, et al. Spironolactone in combination with an oral contraceptive: an alternative treatment for hirsutism. Br J Obstet Gynecol 1984; 92: 983–5

    Google Scholar 

  13. Board JA, Rosenberg SM, Smeltzer JS. Spironolactone and estrogen-progestin therapy for hirsutism. South Med J 1987; 80: 483–6

    Article  PubMed  CAS  Google Scholar 

  14. Pittaway DE, Maxson WS, Wentz AC. Spironolactone in combination drug therapy for unresponsive hirsutism. Fertil Steril 1985; 43: 878–82

    PubMed  CAS  Google Scholar 

  15. Hammerstein J, Meckies J, Leo-Rossberg I, et al. Use of cyproterone acetate (CPA) in the treatment of acne, hirsutism and virilism. J Steroid Biochem 1975; 6: 827–36

    Article  PubMed  CAS  Google Scholar 

  16. Underhill R, Dewhurst J. Further clinical experience in the treatment of hirsutism with cyproterone acetate. Br J Obstet Gynecol 1979; 86: 139–41

    Article  CAS  Google Scholar 

  17. Belisle S, Love EJ. Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study. Fertil Steril 1986; 46: 1015–20

    PubMed  CAS  Google Scholar 

  18. Kuttenn F, Rigaud C, Wright F, et al. Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17β-estradiol. J Clin Endocrinol Metab 1980; 51: 1107–11

    Article  PubMed  CAS  Google Scholar 

  19. Carmina E, Lobo RA. Effect of the estrogen dose in the treatment of hirsutism using cyproterone acetate. Obstet Gynecol. In press

  20. Venturoli S, Marescalchi O, Colombo FM, 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 Metab 1999; 84: 1304–10

    Article  PubMed  CAS  Google Scholar 

  21. Vexiau P, Bourdou P, Fiet J, et al. 17β-estradiol: oral or parenteral administration in hyperadrogenic women? Metabolic tolerance in association with cyproterone acetate. Fertil Steril 1995; 63: 508–15

    PubMed  CAS  Google Scholar 

  22. Carmina E, Lobo RA. Polycystic Ovary Syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 1999; 84: 1897–9

    Article  PubMed  CAS  Google Scholar 

  23. Barth J, Cherry CA, Wojnarowska F, et al. Cyproterone acetate for severe hirsutism: results of a double binding dose ranging study. Clin Endocrinol (Oxf) 1991; 35: 5–10

    Article  CAS  Google Scholar 

  24. Carmina E, Lobo RA. Gonadotrophin releasing hormone agonist therapy for hirsutism is a effective as high dose cyproterone acetate but results in a longer remission. Hum Reprod 1997; 12: 663–6

    Article  PubMed  CAS  Google Scholar 

  25. Sherwin BN, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in surgical menopause. Psychosom Med 1997; 47: 339–51

    Google Scholar 

  26. Simard J, Luthy I, Guay J, et al. Characteristics of interaction of the antiandrogen flutamide with the androgen receptor in various target tissues. Mol Cell Endocrinol 1986; 44: 261–70

    Article  PubMed  CAS  Google Scholar 

  27. Cusan L, Dupont A, Belanger A, et al. Treatment of hirsutism with the pure antiandrogen flutamide. J Am Acad Dermatol 1990; 23: 462–9

    Article  PubMed  CAS  Google Scholar 

  28. Motta T, Maggi G, Perra M, et al. Flutamide in the treatment of hirsutism. Int J Gynaecol Obstet 1991; 36: 155–7

    Article  PubMed  CAS  Google Scholar 

  29. Marconides JAM, Minnani SL, Luthold WW, et al. Treatment of hirsutism in women with flutamide. Fertil Steril 1992; 57: 543–7

    Google Scholar 

  30. Ayub M, Levell MJ. Inhibition of rat testicular 17α-hydroxylase and 17,20-lyase activities by antiandrogens (flutamide, hydroxyflutamide, RU23908, cyproterone acetate) in vitro. J Steroid Biochem 1987; 28: 43–7

    Article  PubMed  CAS  Google Scholar 

  31. Brochu M, Belanger A, Dupont A, et al. Effects of flutamide and aminoglutethimide on plasma 5α-reduced steroid glucuronide concentrations in castrated patients with cancer of the prostate. J Steroid Biochem 1987; 28: 619–22

    Article  PubMed  CAS  Google Scholar 

  32. Moghetti P, Castello R, Negri C, et al. Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor blockade. Fertil Steril 1995; 64: 511–7

    PubMed  CAS  Google Scholar 

  33. Muderris II, Bayram F, Sahin Y, et al. The efficacy of 250 mg/day flutamide in the treatment of patients with hirsutism. Fertil Steril 1996; 66: 220–2

    PubMed  CAS  Google Scholar 

  34. Gomez JL, Dupont A, Cusan L, et al. Incidence of liver toxicity associated with the use of flutamide in prostate cancer patients. Am J Med 1992; 92: 465–70

    Article  PubMed  CAS  Google Scholar 

  35. Wysowski DK, Freiman JP, Tourtelot JB, et al. Fatal and nonfatal hepatotoxicity associated with flutamide. Ann Intern Med 1993; 118: 860–4

    PubMed  CAS  Google Scholar 

  36. Wysowski DK, Foucroy JL. Flutamide hepatotoxicity. J Urol 1996; 155: 209

    Article  PubMed  CAS  Google Scholar 

  37. Lobo RA, Goebelsmann U, Horton R. Evidence for the importance of peripheral tissue events in the development of hirsutism in polycystic ovary syndrome. J Clin Endocrinol Metab 1983; 57: 393–7

    Article  PubMed  CAS  Google Scholar 

  38. Serafini P, Ablan F, Lobo RA. 5α-reductase activity in the genital skin of hirsute women. J Clin Endocrinol Metab 1985; 60: 349–55

    Article  PubMed  CAS  Google Scholar 

  39. Matteri RK, Stanczyk FZ, Gentzscein EE, et al. Androgen sulfate and glucuronide conjugates in nonhirsute and hirsute women with polycystic ovary syndrome. Am J Obstet Gynecol 1989; 161: 1704–9

    PubMed  CAS  Google Scholar 

  40. Russel DW, Wilson JD. Steroid 5α-reductase: two genes, two enzymes. Annu Rev Biochem 1994; 63: 25–61

    Article  Google Scholar 

  41. Courchay G, Boyera N, Bernard BA, et al. Messenger RNA expression of steroidogenesis enzyme subtypes in the human pilosebaceous unit. Skin Pharmacol 1996; 9: 169–76

    Article  PubMed  CAS  Google Scholar 

  42. Carmina E. Role of 5α-reductase isoenzymes in the pathogenesis of acne and hirsutism. In: Dastidar KG, Dastidar SG, Chowdurry NNR, editors. Proceedings of the International Conference on Advanced Reproductive Medicine; 1997; Calcutta, 154–62

  43. Stoner E. The clinical development of a 5α-reductase inhibitor, finasteride. J Steroid Biochem Mol Biol 1990; 37: 375–8

    Article  PubMed  CAS  Google Scholar 

  44. Rittmaster RS. Finasteride. N Engl J Med 1994; 330: 120–5

    Article  PubMed  CAS  Google Scholar 

  45. Fruzzetti F, De Lorenzo D, Parrini D, et al. Effects of finasteride, a 5-reductase inhibitor, on circulating androgens and gonadotropin secretion in hirsute women. J Clin Endocrinol Metab 1994; 79: 831–5

    Article  PubMed  CAS  Google Scholar 

  46. Wang IL, Morris RS, Chang L, et al. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 1995; 80: 233–8

    Article  Google Scholar 

  47. Carmina E. Prevalence of idiopathic hirsutism. Eur J Endocrinol 1998; 139: 424–7

    Article  Google Scholar 

  48. Chang FJ, Laufer LR, Meldrum DR, et al. Steroid secretion in polycystic ovarian disease after ovarian suppression by a long acting gonadotropin releasing hormone agonist. J Clin Endocrinol Metab 1983; 56: 897–904

    Article  PubMed  CAS  Google Scholar 

  49. DeFazio J, Meldrum DR, Laufer L, et al. Induction of hot flashes in menopausal women treated with a long acting GnRH-agonist. J Clin Endocrinol Metab 1983; 56: 445–8

    Article  PubMed  CAS  Google Scholar 

  50. Johansen J, Riis BL, Hassager C, et al. The effect of a gonadotropin releasing hormone agonist analog (nafarelin) on bone metabolism. J Clin Endocrinol Metab 1988; 67: 701–6

    Article  PubMed  CAS  Google Scholar 

  51. Carmina E, Janni A, Lobo RA. Physiological estrogen replacement may enhance the effectiveness of the gonadotropin releasing hormone agonist in the treatment of hirsutism. J Clin Endocrinol Metab 1994; 78: 126–30

    Article  PubMed  CAS  Google Scholar 

  52. Azziz RA, Ochoa TM, Bradley EL, et al. Leuprolide and estrogen versus oral contraceptive for the treatment of hirsutism: a prospective randomized study. J Clin Endocrinol Metab 1995; 80: 3406–11

    Article  PubMed  CAS  Google Scholar 

  53. Elkind-Hirsch KI, Anania C, Mack M, et al. Combination gonadotropin releasing hormone agonist and oral contraceptive therapy improves treatment of hirsute women with ovarian hyperandrogenism. Fertil Steril 1995; 63: 970–8

    PubMed  CAS  Google Scholar 

  54. Sugimoto AK, Hodsman AB, Nisker JA. Long term gonadotropin releasing hormone agonist with standard postmenopausal estrogen replacement failed to prevent vertebral bone loss in premenopausal women. Fertil Steril 1993; 60: 672–4

    PubMed  CAS  Google Scholar 

  55. Carmina E, Lobo RA. Steroid supplementation of GnRH analog in ovarian hyperandrogenism. In: Filicori M, Flamigni C, editors. Treatment with GnRH analogs: controversies and perspectives. New York: Parthenon Publishing Group, 1996: 115–21

    Google Scholar 

  56. Porcile A, Gallardo E. Long term treatment of hirsutism: desogestrel compared with cyproterone acetate in oral contraceptives. Fertil Steril 1991; 55: 877–81

    PubMed  CAS  Google Scholar 

  57. Creatsas G, Koliopoulos C, Mastorakos G. Combined oral contraceptive treatment of adolescent girls with polycistic ovary syndrome. Lipid profile. Ann NY Acad Sci 2000; 900: 245–52

    Article  PubMed  CAS  Google Scholar 

  58. Givens JR, Andersen RN, Wiser WL, et al. The effectiveness of two oral contraceptives in suppressing plasma androstenedione, testosterone, LH and FSH and in stimulating plasma testosterone binding capacity in hirsute women. Am J Obstet Gynecol 1975; 124: 333–9

    Google Scholar 

  59. Lobo RA, Carmina E. Androgen excess. In: Lobo RA, Mishell Jr DR, et al., editors. Infertility, contraception and reproductive endocrinology. Oxford: Blackwell Publishing, 1997: 341–62

    Google Scholar 

  60. Wild RA, Umstot ES, Andersen RN, et al. Adrenal function in hirsutism. II. Effect of an oral contraceptive. J Clin Endocrinol Metab 1982; 54: 676–83

    Article  PubMed  CAS  Google Scholar 

  61. Rittmaster RS, Loriaux DL, Cutler Jr GB. Sensitivity of adrenal androgens to dexamethasone suppression in hirsute women. J Clin Endocrinol Metab 1985; 81: 462–6

    Article  Google Scholar 

  62. Carmina E, Caputo A, Malizia G, et al. Long term dexamethasone treatment of hirsutism. In: Genazzani AR, Volpe A, Facchinetti F, editors. Research on gynecological endocrinology. Canforth: Parthenon Publishing, 1987: 205–8

    Google Scholar 

  63. Redmond G, Gidwani G, Gupta M, et al. Treatment of androgenic disorders with dexamethasone. Dose response relationship for suppression of dehydroepiandrosterone sulfate. J Am Acad Dermatol 1990; 22: 91–3

    Article  PubMed  CAS  Google Scholar 

  64. Azziz R. Glucocorticoid suppression in the treatment of androgen excess. In: Azziz R, Nestler JE, Dewailly D, editors. Androgen excess disorders in women. Philadelphia (PA): Lippincott-Raven Publishing, 1997: 737–47

    Google Scholar 

  65. Carmina E, Lobo RA. The addiction of dexamethasone to antiandrogen therapy for hirsutism prolongs the duration of remission. Fertil Steril 1998; 69: 1075–9

    Article  PubMed  CAS  Google Scholar 

  66. Barman Balfour JA, McClellan KM. Topical eflornithine. Am J Clin Dermatol 2001. In press

    Google Scholar 

  67. Schrode K, Huber F, Staszak J, et al. Randomized, double-blind, vehicle controlled safety and efficacy evaluation of eflornithine 15% cream in the treatment of women with excessive facial hair. 58th Annual Meeting of The American Academy of Dermatology; 2000 Mar 10-15; San Francisco

  68. Rittmaster RS. Medical treatment of androgen dependent hirsutism. J Clin Endocrinol Metab 1995; 80: 2559–63

    Article  PubMed  CAS  Google Scholar 

  69. Spritzer PM, Lisboa KO, Mattiello S, et al. Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol (Oxf) 2000; 52: 587–94

    Article  CAS  Google Scholar 

  70. Kokaly W, Mc Kenna T. Relapse of hirsutism following long-term successful treatment with oestrogen-progestogen combination. Clin Endocrinol (Oxf) 2000; 52: 379–82

    Article  CAS  Google Scholar 

  71. Cusan L, Dupont A, Gomez JL, et al. Comparison of flutamide and spironolactone in the treatment of hirsutism: a randomized controlled trial. Fertil Steril 1994; 61: 281–7

    PubMed  CAS  Google Scholar 

  72. Erenus M, Yucelten D, Durmusuglu F, et al. Comparison of finasteride vs spironolactone in the treatment of idiopathic hirsutism. Fertil Steril 1997; 68: 1000–3

    Article  PubMed  CAS  Google Scholar 

  73. Fruzzetti F, Bersi C, Parrini D, et al. Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects. Fertil Steril 1999; 71: 445–51

    Article  PubMed  CAS  Google Scholar 

  74. Falsetti L, Gambera A, Lagrenzi L, et al. Comparison of finasteride versus flutamide in the treatment of hirsutism. Eur J Endocrinol 1999; 41: 361–7

    Article  Google Scholar 

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Carmina, E. A Risk-Benefit Assessment of Pharmacological Therapies for Hirsutism. Drug-Safety 24, 267–276 (2001). https://doi.org/10.2165/00002018-200124040-00004

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