Comparison of the clinical efficacy of flutamide and spironolactone plus ethinyloestradiol/cyproterone acetate in the treatment of hirsutism: A randomised controlled study
Introduction: Hirsutism is commonly a consequence of ovarian androgen over-production. Polycystic ovary syndrome (PCOS) or peripheral hypersensitivity to normal androgen circulating levels (idiopathic hirsutism) can be the underlying cause. Several drugs with anti-androgenic properties, such as cyproterone acetate (CPA), spironolactone and flutamide have been used to treat hirsutism, but the efficacy of these drugs has yet to be fully elucidated. The objective of this study was to compare the effectiveness of flutamide, and spironolactone plus a combination tablet of 2 mg CPA/35 μg ethinyloestradiol (EE) in the treatment of hirsutism.
Methods: A prospective randomised clinical study was conducted in a tertiary care hospital setting. Twenty-nine women with hirsutism as a consequence of PCOS or idiopathic hirsutism were randomly assigned to receive 250 mg/day flutamide alone or 100 mg/day spironolactone plus a combination tablet of 2 mg CPA/35 μg EE, for 6 months. Patients’ hormonal and lipid profiles were evaluated. Hirsutism was graded according to the modified Ferriman-Gallwey (mF-G) score, and side effects were monitored.
Results: A significant decrease in mF-G scores was observed in the flutamide (from 11.2±3.3 to 7.6±4.0) and spironolactone plus CPA/EE (from 9.9±1.9 to 7.1±2.0) groups. However, there was no statistically significant difference between the two groups. After flutamide therapy, total cholesterol levels decreased significantly but no significant change was observed in any other lipid parameters or in the patients’ hormone profiles. After spironolactone plus CPA/EE therapy, levels of luteinising hormone, total testosterone and free testosterone significantly decreased and triglyceride levels increased. No patients were found to have abnormal liver function test results.
Conclusion: Flutamide and spironolactone plus CPA/EE are effective drugs in the treatment of hirsutism.
- Jeffcoate W. The treatment of women with hirsutism. Clin Endocrinol (Oxf). 1993;39:143–150. CrossRef
- Rittmaster RS. 1995 medical treatment of androgen-dependent hirsutism. J Clin Endocrinol Metab. 1995;80:2559–2563. CrossRef
- Aziz R, Ochoa TM, Bradley EL, Potter HD, Boots LR. Luprolide and estrogen vs oral contraceptive pills for the treatment of hirsutism: a prospective randomized study. J Clin Endocrinol Metab. 1995; 80:3406–3411. CrossRef
- Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab. 1987;65:499–507. CrossRef
- Moghetti P, Castello R, Negri C, et al. Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior. Fertil Steril. 1995;64:511–517.
- Müderris II, Bayram F, Sahin Y, Kelestimur F. A comparison between two doses of flutamide (250mg/d and 500mg/d) in the treatment of hirsutism. Fertil Steril. 1997;68:644–647. CrossRef
- de Leo V, la Marca A, Lanzetta D, Cariello PL, D’Antona D, Morgante G. Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF). Clin Endocrinol (Oxf). 1998;49:85–89. CrossRef
- Dodin S, Faure N, Cerdin I, et al. Clinical efficacy and safety of low-dose flutamide alone and combined with oral contraceptive for the treatment of idiopatic hirsutism. Clin Endocrinol. 1995;43:575–582. CrossRef
- Fruzzetti F, Bersi C, Parrini D, Ricci C, Genazzani R. Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects. Fertil Steril. 1999;71:4445–4451. CrossRef
- Pucci E, Genazzani AD, Monzani F, Lippi F, et al. Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome. Gynecol Endocrinol. 1995;90:221–228.
- Paoletti AM, Cagnacci A, Orru M, Ajossa S, Guerriero S, Melis GB. Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism. Fertil Steril. 1999;72:448–453. CrossRef
- Mercurio MG. Managing patient with hirsutism. Hosp Med. 1998;34:41–51.
- McMullen GR, Van Herle AJ. Hirsutism and the effectiveness of spironolactone in its management. J Endocrinol Invest. 1993;16:925.
- Lobo RA, Shoupe D, Serafini P, Brinton D, Horton R. The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. Fertil Steril. 1985;43:200–205.
- Biffignandi P, Massuchettic C, Molinatti GM. Female hirsutism pathophysiological considerations and therapeutic implications. Endocrinol Rev. 1984;5:498–513. CrossRef
- Belisle S, Love EJ. Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study. Fertil Steril. 1986;46:1015–1020.
- Venturoli S, Ravaioli B, Bagnoli A, et al. Contraceptive and therapeutic effectiveness of two low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsute patients. Eur J Contrac Reprod Health Care. 1998:3:29–33. CrossRef
- Hatch R, Rosenfield R, Kim MH, Treway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. 1981;140:815–830.
- Moghetti P, Tosi F, Tosti A, 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. 2000;85:89–94. CrossRef
- Spritzer PM, Lisboa KO, Mattiello S, Lhullier F. Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol. 2000;52:587–594. CrossRef
- Lumachi F, Rondinone R. Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism. Fertil Steril. 2003;79:942–946. CrossRef
- Inal M, Yildirim Y, Taner CE. Comparison of the clinical efficacy of flutamide and spironolactone plus Diane 35 in the treatment of idiopathic hirsutism: a randomized controlled study. Fertil Steril. 2005; 84:1693–1697. CrossRef
- Beigi A, Sobhi A, Zarrinkoub F. Finasteride versus cyproterone acetate-estrogen regimens in the treatment of hirsutism. Int J Gynaecol Obstet. 2004;87:29–33. CrossRef
- Falsetti L, Pasinetti E. Effects of long-term administration of an oral contraceptive containing ethinylestradiol and cyproterone acetate on lipid metabolism in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 1995;74:56–60. CrossRef
- Mastorakos G, Koliopoulos C, Creatsas G. Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril. 2002; 77:919–927. CrossRef
- Comparison of the clinical efficacy of flutamide and spironolactone plus ethinyloestradiol/cyproterone acetate in the treatment of hirsutism: A randomised controlled study
Advances in Therapy
Volume 25, Issue 4 , pp 321-328
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- 1. Department of Endocrinology and Metabolic Diseases, Fatih University Faculty of Medicine, Isci Bloklari Mah 420. Sokak, 52/11 Yuzuncuyil, Ankara, Turkey
- 2. Ankara Postgraduate Training Hospital, Ankara, Turkey
- 3. Department of Nephrology, Fatih University Faculty of Medicine, Ankara, Turkey