Treatment of hirsutism
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- Jeffrey Chang, MD
Jeffrey Chang, MD
- University of California, San Diego
- Section Editors
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
- William F Crowley, Jr, MD
William F Crowley, Jr, MD
- Section Editor — Female Reproductive Endocrinology
- Daniel K Podolsky Professor of Medicine
- Harvard Medical School
Hirsutism, defined as excessive male-pattern hair growth in a woman, affects between 5 and 10 percent of women of reproductive age. In some cases, hirsutism is mild and requires only reassurance and perhaps cosmetic therapy, while in others, it causes significant distress and requires more extensive intervention.
The treatment of hirsutism will be reviewed here. The pathogenesis, causes, and evaluation of hirsutism are discussed separately. Direct methods of hair removal are reviewed briefly here and in greater detail elsewhere. (See "Pathophysiology and causes of hirsutism" and "Evaluation of premenopausal women with hirsutism" and "Removal of unwanted hair".)
Hirsutism is a clinical diagnosis defined by the presence of excess terminal hair growth (dark, coarse hairs) in androgen-dependent areas (eg, upper lip, chin, midsternum, upper abdomen, back, and buttocks) [1,2]. Hair growth can be graded as either normal or excessive based upon the Ferriman-Gallwey score. There are several conditions characterized by generalized or "excess" hair growth that do not represent hirsutism and do not require biochemical evaluation with serum androgens, including hypertrichosis and "unwanted hair" (any hair growth [usually light, unpigmented facial hair] that the patient finds bothersome). This type of hair is not a sign of androgen excess. (See "Evaluation of premenopausal women with hirsutism", section on 'Other types of excess hair'.)
Hirsutism is an important clinical problem that affects approximately 5 to 10 percent of women . It is important to evaluate and treat because:
●It is associated with significant emotional distress and depression [4-6]. (See "Evaluation of premenopausal women with hirsutism", section on 'Emotional distress/depression'.)
- Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005; 353:2578.
- FERRIMAN D, GALLWEY JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961; 21:1440.
- Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998; 83:3078.
- Clayton WJ, Lipton M, Elford J, et al. A randomized controlled trial of laser treatment among hirsute women with polycystic ovary syndrome. Br J Dermatol 2005; 152:986.
- Lipton MG, Sherr L, Elford J, et al. Women living with facial hair: the psychological and behavioral burden. J Psychosom Res 2006; 61:161.
- Hahn S, Janssen OE, Tan S, et al. Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome. Eur J Endocrinol 2005; 153:853.
- Souter I, Sanchez LA, Perez M, et al. The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol 2004; 191:1914.
- Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev 2000; 21:363.
- Di Fede G, Mansueto P, Pepe I, et al. High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms. Fertil Steril 2010; 94:194.
- Martin KA, Chang RJ, Ehrmann DA, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93:1105.
- Cheewadhanaraks S, Peeyananjarassri K, Choksuchat C. Clinical diagnosis of hirsutism in Thai women. J Med Assoc Thai 2004; 87:459.
- Pasch L, He SY, Huddleston H, et al. Clinician vs Self-ratings of Hirsutism in Patients With Polycystic Ovarian Syndrome: Associations With Quality of Life and Depression. JAMA Dermatol 2016; 152:783.
- DeUgarte CM, Woods KS, Bartolucci AA, Azziz R. Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism. J Clin Endocrinol Metab 2006; 91:1345.
- Cosma M, Swiglo BA, Flynn DN, et al. Clinical review: Insulin sensitizers for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. J Clin Endocrinol Metab 2008; 93:1135.
- Spritzer PM, Lisboa KO, Mattiello S, Lhullier F. Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol (Oxf) 2000; 52:587.
- Burkman RT Jr. The role of oral contraceptives in the treatment of hyperandrogenic disorders. Am J Med 1995; 98:130S.
- Saeed, R, Akram, J, Changezi, HE, Saeed, M. Specialist 1993; 9:109.
- Porcile A, Gallardo E. Long-term treatment of hirsutism: desogestrel compared with cyproterone acetate in oral contraceptives. Fertil Steril 1991; 55:877.
- Zimmerman Y, Eijkemans MJ, Coelingh Bennink HJ, et al. The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis. Hum Reprod Update 2014; 20:76.
- White T, Jain JK, Stanczyk FZ. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. Am J Obstet Gynecol 2005; 192:2055.
- Givens JR, Andersen RN, Wiser WL, Fish SA. Dynamics of suppression and recovery of plasma FSH, LH, androstenedione and testosterone in polycystic ovarian disease using an oral contraceptive. J Clin Endocrinol Metab 1974; 38:727.
- 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 1976; 124:333.
- Raj SG, Raj MH, Talbert LM, et al. Normalization of testosterone levels using a low estrogen-containing oral contraceptive in women with polycystic ovary syndrome. Obstet Gynecol 1982; 60:15.
- Dewis P, Petsos P, Newman M, Anderson DC. The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol. Clin Endocrinol (Oxf) 1985; 22:29.
- Vermeulen A, Stoïca T, Verdonck L. The apparent free testosterone concentration, an index of androgenicity. J Clin Endocrinol Metab 1971; 33:759.
- Pardridge WM, Mietus LJ, Frumar AM, et al. Effects of human serum on transport of testosterone and estradiol into rat brain. Am J Physiol 1980; 239:E103.
- Mathur RS, Moody LO, Landgrebe SC, et al. Sex-hormone-binding globulin in clinically hyperandrogenic women: association of plasma concentrations with body weight. Fertil Steril 1982; 38:207.
- Zhang YW, Stern B, Rebar RW. Endocrine comparison of obese menstruating and amenorrheic women. J Clin Endocrinol Metab 1984; 58:1077.
- Easterling WE Jr, Talbert LM, Potter HD. Serum testosterone levels in the polycystic ovary syndrome. Effect of an estrogen-progestin on protein binding of testosterone. Am J Obstet Gynecol 1974; 120:385.
- Cullberg G, Hamberger L, Mattsson LA, et al. Effects of a low-dose desogestrel-ethinylestradiol combination on hirsutism, androgens and sex hormone binding globulin in women with a polycystic ovary syndrome. Acta Obstet Gynecol Scand 1985; 64:195.
- Bowles SM, Mills RJ. Sex hormone binding globulin: effect of synthetic steroids on the assay and effect of oral contraceptives. Ann Clin Biochem 1981; 18:226.
- Sánchez LA, Pérez M, Centeno I, et al. Determining the time androgens and sex hormone-binding globulin take to return to baseline after discontinuation of oral contraceptives in women with polycystic ovary syndrome: a prospective study. Fertil Steril 2007; 87:712.
- Casey JH. Chronic treatment regimens for hirsutism in women: effect on blood production rates of testosterone and on hair growth. Clin Endocrinol (Oxf) 1975; 4:313.
- Kim MH, Rosenfield RL, Hosseinian AH, Schneir HG. Ovarian hyperandrogenism with normal and abnormal histologic findings of the ovaries. Am J Obstet Gynecol 1979; 134:445.
- Fern M, Rose DP, Fern EB. Effect of oral contraceptives on plasma androgenic steroids and their precursors. Obstet Gynecol 1978; 51:541.
- Wiebe RH, Morris CV. Effect of an oral contraceptive on adrenal and ovarian androgenic steroids. Obstet Gynecol 1984; 63:12.
- Wild RA, Umstot ES, Andersen RN, Givens JR. Adrenal function in hirsutism. II. Effect of an oral contraceptive. J Clin Endocrinol Metab 1982; 54:676.
- Carr BR, Parker CR Jr, Madden JD, et al. Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment. J Clin Endocrinol Metab 1979; 49:346.
- Muhn P, Fuhrmann U, Fritzemeier KH, et al. Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci 1995; 761:311.
- Batukan C, Muderris II, Ozcelik B, Ozturk A. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol 2007; 23:38.
- Kriplani A, Periyasamy AJ, Agarwal N, et al. Effect of oral contraceptive containing ethinyl estradiol combined with drospirenone vs. desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome. Contraception 2010; 82:139.
- Bhattacharya SM, Jha A. Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome. Fertil Steril 2012; 98:1053.
- Breitkopf DM, Rosen MP, Young SL, Nagamani M. Efficacy of second versus third generation oral contraceptives in the treatment of hirsutism. Contraception 2003; 67:349.
- Knopp RH, Broyles FE, Cheung M, et al. Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel. Contraception 2001; 63:1.
- Van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. Cochrane Database Syst Rev 2003; :CD001125.
- Brown J, Farquhar C, Lee O, et al. Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev 2009; :CD000194.
- Swiglo BA, Cosma M, Flynn DN, et al. Clinical review: Antiandrogens for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. J Clin Endocrinol Metab 2008; 93:1153.
- Lobo RA, Shoupe D, Serafini P, et al. The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. Fertil Steril 1985; 43:200.
- Wong 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.
- 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.
- 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.
- 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.
- Müderris II, Bayram F, Güven M. A prospective, randomized trial comparing flutamide (250 mg/d) and finasteride (5 mg/d) in the treatment of hirsutism. Fertil Steril 2000; 73:984.
- Wysowski DK, Freiman JP, Tourtelot JB, Horton ML 3rd. Fatal and nonfatal hepatotoxicity associated with flutamide. Ann Intern Med 1993; 118:860.
- Wysowski DK, Fourcroy JL. Flutamide hepatotoxicity. J Urol 1996; 155:209.
- Brahm J, Brahm M, Segovia R, et al. Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature. Ann Hepatol 2011; 10:93.
- Bruni V, Peruzzi E, Dei M, et al. Hepatotoxicity with low- and ultralow-dose flutamide: a surveillance study on 203 hyperandrogenic young females. Fertil Steril 2012; 98:1047.
- Ibáñez L, de Zegher F. Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity. J Clin Endocrinol Metab 2004; 89:1592.
- Ibáñez L, De Zegher F. Flutamide-metformin therapy to reduce fat mass in hyperinsulinemic ovarian hyperandrogenism: effects in adolescents and in women on third-generation oral contraception. J Clin Endocrinol Metab 2003; 88:4720.
- Ibáñez L, De Zegher F. Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity. Hum Reprod 2004; 19:1725.
- Ibáñez L, Ong K, Ferrer A, et al. Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adolescents with ovarian hyperandrogenism. J Clin Endocrinol Metab 2003; 88:2600.
- Paradisi R, Venturoli S. Retrospective observational study on the effects and tolerability of flutamide in a large population of patients with various kinds of hirsutism over a 15-year period. Eur J Endocrinol 2010; 163:139.
- Anonymous. Germany's cyproterone warning. Lancet 1995; 345:979.
- Heinemann LA, Will-Shahab L, van Kesteren P, et al. Safety of cyproterone acetate: report of active surveillance. Pharmacoepidemiol Drug Saf 1997; 6:169.
- Kokaly W, McKenna TJ. Relapse of hirsutism following long-term successful treatment with oestrogen-progestogen combination. Clin Endocrinol (Oxf) 2000; 52:379.
- Koulouri O, Conway GS. Management of hirsutism. BMJ 2009; 338:b847.
- Somani N, Turvy D. Hirsutism: an evidence-based treatment update. Am J Clin Dermatol 2014; 15:247.
- "The Pink Sheet". August 7, 2000; 62:7.
- Wolf JE Jr, Shander D, Huber F, et al. Randomized, double-blind clinical evaluation of the efficacy and safety of topical eflornithine HCl 13.9% cream in the treatment of women with facial hair. Int J Dermatol 2007; 46:94.
- Smith SR, Piacquadio DJ, Beger B, Littler C. Eflornithine cream combined with laser therapy in the management of unwanted facial hair growth in women: a randomized trial. Dermatol Surg 2006; 32:1237.
- Hamzavi I, Tan E, Shapiro J, Lui H. A randomized bilateral vehicle-controlled study of eflornithine cream combined with laser treatment versus laser treatment alone for facial hirsutism in women. J Am Acad Dermatol 2007; 57:54.
- Morin-Papunen LC, Vauhkonen I, Koivunen RM, et al. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 2000; 85:3161.
- Costello M, Shrestha B, Eden J, et al. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst Rev 2007; :CD005552.
- Spritzer P, Billaud L, Thalabard JC, et al. Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia. J Clin Endocrinol Metab 1990; 70:642.
- Frank-Raue K, Junga G, Raue F, et al. [Therapy of hirsutism in females with adrenal enzyme defects of steroid hormone biosynthesis: comparison of dexamethasone with cyproterone acetate]. Klin Wochenschr 1990; 68:597.
- Carmina E, Lobo RA. Peripheral androgen blockade versus glandular androgen suppression in the treatment of hirsutism. Obstet Gynecol 1991; 78:845.
- Carmina E, Lobo RA. The addition of dexamethasone to antiandrogen therapy for hirsutism prolongs the duration of remission. Fertil Steril 1998; 69:1075.
- Rittmaster RS, Thompson DL. Effect of leuprolide and dexamethasone on hair growth and hormone levels in hirsute women: the relative importance of the ovary and the adrenal in the pathogenesis of hirsutism. J Clin Endocrinol Metab 1990; 70:1096.
- Gambineri A, Patton L, Vaccina A, et al. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab 2006; 91:3970.
- Mitkov M, Pehlivanov B, Terzieva D. Combined use of metformin and ethinyl estradiol-cyproterone acetate in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2005; 118:209.
- Carmina E, Koyama T, Chang L, et al. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992; 167:1807.
- Gomez F, Ramelet AA, Rüedi B, Mühlemann M. Lack of effect of a spironolactone-containing cream on hair growth in hirsute women. Dermatologica 1987; 174:102.
- GENERAL PRINCIPLES
- OVERVIEW OF APPROACH
- Drug therapy or hair removal?
- Pharmacologic therapy
- - Oral contraceptives
- Mechanisms of action in hyperandrogenism/hirsutism
- - Choice of pill
- - Monitoring
- Good cosmetic response
- Suboptimal response
- - Add antiandrogen to OC
- Severe symptoms causing distress
- - Antiandrogen therapy
- Choice of antiandrogen
- Duration of drug therapy
- - Direct hair removal methods
- - Treatments not recommended
- - Special populations
- Coexisting depression
- Women with NCCAH
- Postmenopausal women
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS