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No. 350-Hirsutism: Evaluation and Treatment

  • Kimberly Liu
    Correspondence
    Corresponding Author: Dr. Kimberly Liu; University of Toronto, Department of Obstetrics and Gynecology, Toronto ON
    Affiliations
    Toronto, ON
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  • Tarek Motan
    Affiliations
    Edmonton, AB
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  • Paul Claman
    Affiliations
    Ottawa, ON
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  • Author Footnotes
    ∗ Members of the Reproductive Endocrinology and Infertility Committee: Belina Carranza-Mamane, MD, Sherbrooke, QC; Anthony Cheung (Co-chair), MD, Vancouver, BC; Catherine Dwyer, RN, Toronto, ON; James Graham, MD, Calgary, AB; Sarah Healey, MD, St. John’s, NL; Robert Hemmings, MD, Montréal, QC; Kimberly Liu, MD, Toronto, ON; Tarek Motan, MD, Edmonton, AB; Sony Sierra (Co-chair), MD, Toronto, ON; David Smithson, MD, Ottawa, ON; Tannys Vause, MD, Ottawa, ON; Benjamin Wong, MD, Calgary, AB. Disclosure statements have been received from all principal authors.

      Abstract

      Objectives

      To review the etiology, evaluation, and treatment of hirsutism.

      Evaluation

      A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment.

      Treatment

      Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response.

      Outcomes

      At least 6 to 9 months of therapy are required to produce improvement in hirsutism.

      Evidence

      The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination.

      Recommendations

      Hirsutism can be slowly but dramatically improved with a 3-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes, including weight loss and exercise, will lower serum androgen levels and improve self-esteem in patients with polycystic ovary syndrome. The patient should be educated regarding the associated health problems or long-term medical consequences of hyperandrogenism, particularly in the context of polycystic ovary syndrome, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease.

      Summary Statements

      • 1.
        The Ferriman-Gallwey score can be used in the assessment of hirsutism to help quantify the problem and help assess response to treatment. A score ≥8 represents excessive hair growth, with mild hirsutism <15, moderate 16 to 25, and severe >25 (II-2).
      • 2.
        Insulin resistance and hyperinsulinemia may lead to hyperandrogenism in women with polycystic ovary syndrome (PCOS) (II).
      • 3.
        Non-classical congenital adrenal hyperplasia often presents with hirsutism and has a clinical picture similar to that of PCOS. However, the prevalence of non-classical congenital adrenal hyperplasia is very low outside of specific high-risk ethnic groups (II-2).
      • 4.
        Hirsutism can be classified into 1 of 3 groups based on etiology: hyperandrogenic hirsutism (including polycystic ovarian syndrome or androgen-secreting tumours), non-androgenic hirsutism (including medication-induced hirsutism), and idiopathic hirsutism (II-3).
      • 5.
        Polycystic ovarian syndrome is the most common cause of hirsutism, with idiopathic hirsutism being the second most common cause (II-2).
      • 6.
        Although adolescents may present with hirsutism, the diagnosis of PCOS in these young women is controversial given that the diagnostic features of PCOS may be normal pubertal physiologic events (III).
      • 7.
        The most effective therapy for hirsutism is multimodal and combines physical hair removal techniques and medical therapies. At least 6 months of medical therapy are required to see a significant improvement in hirsutism (II-2).
      • 8.
        Only laser hair removal and electrolysis produce permanent hair reduction, and hair growth tends to recur after stopping medical therapy (II-2).

      Recommendations

      • 1.
        Women presenting with hirsutism should be evaluated with a focused history, physical examination, and appropriate investigations to differentiate among the possible etiologies (III-B).
      • 2.
        Laboratory investigations for women with moderate to severe hirsutism should include total testosterone, although the benefit in mild hirsutism is questionable. Additional testing is indicated for women with irregular menses and/or signs of hyperandrogenism or other endocrinopathies (III-B).
      • 3.
        Referral for evaluation by an endocrinologist or reproductive endocrinologist is indicated in the presence of the following: (1) virilisation, (2) serum testosterone or dehydroepiandrosterone sulfate levels more than twice the upper limit of normal, (3) signs or symptoms of Cushing's syndrome, or (4) early menstrual phase serum 17-hydroxyprogesterone levels >6 nmol/L (III-B).
      • 4.
        All patients experiencing hirsutism who desire treatment should be offered combined hormonal contraceptive therapy as first-line therapy, provided they have no contraindications (I-A).
      • 5.
        Mechanical hair removal and/or topical therapy can be offered as first-line therapy or as an adjuvant to medical therapy (I-A).
      • 6.
        Depending on a woman's goals of treatment, anti-androgens should be considered for moderate to severe hirsutism or to ensure an optimal response in milder hirsutism (I-A).
      • 7.
        Anti-androgens can be used in conjunction with combined hormonal contraceptive therapy to enhance treatment efficacy (I-A).
      • 8.
        If a woman on anti-androgen therapy wishes to conceive, anti-androgen therapy should be stopped prior to discontinuing the use of contraception to prevent the potential feminization of a male fetus if pregnancy were to occur (III-B).
      • 9.
        Health care providers assessing women with hirsutism should complete a comprehensive evaluation and, when applicable, explore the long-term health sequelae of hyperandrogenism and polycystic ovary syndrome, including abnormal uterine bleeding, infertility, and metabolic syndrome (III-B).

      Key Words

      Abbreviations:

      17-OHP (17-hydroxyprogesterone), AN (acanthosis nigricans), CAH (congenital adrenal hyperplasia), CHC (combined hormonal contraceptives), CPA (cyproterone acetate), MPA (medroxyprogesterone acetate), NCAH (non-classical congenital adrenal hyperplasia), OC (oral contraceptive), PCOS (polycystic ovary syndrome), SHBG (sex hormone–binding globulin)
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      References

        • Azziz R.
        • Sanchez L.A.
        • Knochenhauer E.S.
        • et al.
        Androgen excess in women: experience with over 1000 consecutive patients.
        J Clin Endocrinol Metab. 2004; 89: 453-462
        • Carmina E.
        • Rosato F.
        • Janni A.
        • et al.
        Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism.
        J Clin Endocrinol Metab. 2006; 91: 2-6
        • Willenberg H.S.
        • Bahlo M.
        • Schott M.
        • et al.
        Helpful diagnostic markers of steroidogenesis for defining hyperandrogenemia in hirsute women.
        Steroids. 2008; 73: 41-46
        • Ferriman D.
        • Gallwey J.D.
        Clinical assessment of body hair growth in women.
        J Clin Endocrinol Metab. 1961; 21: 1440-1447
        • Hatch R.
        • Rosenfield R.L.
        • Kim M.H.
        • et al.
        Hirsutism: implications, etiology, and management.
        Am J Obstet Gynecol. 1981; 140: 815-830
        • Yildiz B.O.
        • Bolour S.
        • Woods K.
        • et al.
        Visually scoring hirsutism.
        Hum Reprod Update. 2010; 16: 51-64
        • Hohl A.
        • Ronsoni M.F.
        • Oliveira M.
        Hirsutism: diagnosis and treatment.
        Arq Bras Endocrinol Metabol. 2014; 58: 97-107
        • Yildiz B.O.
        Diagnosis of hyperandrogenism: clinical criteria.
        Best Pract Res Clin Endocrinol Metab. 2006; 20: 167-176
        • Guyatt G.
        • Weaver B.
        • Cronin L.
        • et al.
        Health-related quality of life in women with polycystic ovary syndrome, a self-administered questionnaire, was validated.
        J Clin Epidemiol. 2004; 57: 1279-1287
        • Loriaux D.L.
        An approach to the patient with hirsutism.
        J Clin Endocrinol Metab. 2012; 97: 2957-2968
        • Erem C.
        Update on idiopathic hirsutism: diagnosis and treatment.
        Acta Clin Belg. 2013; 68: 268-274
        • Martin K.A.
        • Chang R.J.
        • Ehrmann D.A.
        • et al.
        Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline.
        J Clin Endocrinol Metab. 2008; 93: 1105-1120
        • Somani N.
        • Harrison S.
        • Bergfeld W.F.
        The clinical evaluation of hirsutism.
        Dermatol Ther. 2008; 21: 376-391
        • Fritz M.
        Hirsutism.
        in: Fritz Marc A. Speroff Leon Clinical gynecologic endocrinology and infertility. ed 8. Lippincott, William & Wilkins, Philadelphia, PA2011: 533-565
        • Lobo R.
        • Paul W.
        • Goebelsmann U.
        Dehydroepiandrosterone sulphate: an indicator of adrenal androgen function.
        Obstet Gynecol. 1981; 57: 69-72
        • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
        Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
        Fertil Steril. 2004; 81: 19-25
        • Laredo S.
        • Hannah M.
        • Casper R.
        • et al.
        Polycystic ovary syndrome and insulin resistance: new approaches to management, including exercise.
        J Soc Obstet Gynaecol Can. 2001; 23: 306-312
        • Poretsky L.
        • Piper B.
        Insulin resistance, hypersecretion of LH, and a dual-defect hypothesis for the pathogenesis of polycystic ovary syndrome.
        Obstet Gynecol. 1994; 84: 613-621
        • Flier J.S.
        • Eastman R.C.
        • Minaker K.L.
        • et al.
        Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state distinct from the type A and B syndromes.
        Diabetes. 1985; 34: 101-107
        • Barbieri R.L.
        • Ryan K.J.
        Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features.
        Am J Obstet Gynecol. 1983; 147: 90-101
        • Utiger R.D.
        Insulin and the polycystic ovary syndrome.
        N Engl J Med. 1996; 335: 657-658
        • Dunaif A.
        Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.
        Endocr Rev. 1997; 18: 774-800
        • Codner E.
        • Escobar-Morreale H.F.
        Clinical review: hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus.
        J Clin Endocrinol Metab. 2007; 92: 1209-1216
        • Goodman N.F.
        • Cobin R.H.
        • Futterweit W.
        • et al.
        American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 1.
        Endocr Pract. 2015; 21: 1291-1300
        • Goodman N.F.
        • Cobin R.H.
        • Futterweit W.
        • et al.
        American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 2.
        Endocr Pract. 2015; 21: 1415-1426
        • Harrison C.L.
        • Lombard C.B.
        • Moran L.J.
        • et al.
        Exercise therapy in polycystic ovary syndrome: a systematic review.
        Hum Reprod Update. 2011; 17: 171-183
        • Mario F.M.
        • Graff S.K.
        • Spritzer P.M.
        Habitual physical activity is associated with improved anthropometric and androgenic profile in PCOS: a cross-sectional study.
        J Endocrinol Invest. 2017; 40: 377-384
        • Karrer-Voegeli S.
        • Rey F.
        • Reymond M.J.
        • et al.
        Androgen dependence of hirsutism, acne, and alopecia in women: retrospective analysis of 228 patients investigated for hyperandrogenism.
        Medicine. 2009; 88: 32-45
        • McKenna T.J.
        Screening for sinister causes of hirsutism.
        N Engl J Med. 1994; 331: 1015-1016
        • Derksen J.
        • Nagesser S.K.
        • Meinders A.E.
        • et al.
        Identification of virilizing adrenal tumors in hirsute women.
        N Engl J Med. 1994; 331: 968-973
        • New M.I.
        Extensive clinical experience: nonclassical 21-hydroxylase deficiency.
        J Clin Endocrinol Metab. 2006; 91: 4205-4214
        • Falhammar H.
        • Nordenstrom A.
        Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome.
        Endocrine. 2015; 50: 32-50
        • New M.
        • Speiser P.
        Genetics of adrenal steroid 21-hydroxylase deficiency.
        Endocr Rev. 1986; 7: 331-335
        • Moran C.
        • Azziz R.
        • Carmina E.
        • et al.
        21-hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study.
        Am J Obstet Gynecol. 2000; 183: 1468-1474
        • Spritzer P.
        • Billaud L.
        • Thalabard J.C.
        • et al.
        Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia.
        J Clin Endocrinol Metab. 1990; 70: 642-646
        • Schriock E.A.
        • Schriock E.D.
        Treatment of hirsutism.
        Clin Obstet Gynecol. 1991; 34: 852-863
        • Piraccini B.M.
        • Iorizzo M.
        • Rech G.
        • et al.
        Drug-induced hair disorders.
        Curr Drug Saf. 2006; 1: 301-305
        • Escobar-Morreale H.F.
        Diagnosis and management of hirsutism.
        Ann N Y Acad Sci. 2010; 1205: 166-174
        • Azziz R.
        The evaluation and management of hirsutism.
        Obstet Gynecol. 2003; 101: 995-1007
        • Serafini P.
        • Ablan F.
        • Lobo R.A.
        5 alpha-reductase activity in the genital skin of hirsute women.
        J Clin Endocrinol Metab. 1985; 60: 349-355
        • Serafini P.
        • Lobo R.A.
        Increased 5 alpha-reductase activity in idiopathic hirsutism.
        Fertil Steril. 1985; 43: 74-78
        • Lobo R.A.
        Idiopathic hirsutism: fact or fiction.
        Sem Reprod Endocrinol. 1986; 4: 179-183
        • Brodell L.A.
        • Mercurio M.G.
        Hirsutism: diagnosis and management.
        Gend Med. 2010; 7: 79-87
        • Escobar-Morreale H.F.
        • Carmina E.
        • Dewailly D.
        • et al.
        Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society.
        Hum Reprod Update. 2012; 18: 146-170
        • Legro R.S.
        • Schlaff W.D.
        • Diamond M.P.
        • et al.
        Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism.
        J Clin Endocrinol Metab. 2010; 95: 5305-5313
        • Sachdeva S.
        Hirsutism: evaluation and treatment.
        Indian J Dermatol. 2010; 55: 3-7
        • Dessinioti C.
        • Katsambas A.
        Congenital adrenal hyperplasia.
        Dermatoendocrinol. 2009; 1: 87-91
        • Witchel S.F.
        • Oberfield S.
        • Rosenfield R.L.
        • et al.
        The diagnosis of polycystic ovary syndrome during adolescence [e-pub ahead of print].
        Horm Res Paediatr. 2015; 83 (Accessed May 31, 2017): 376-389https://doi.org/10.1159/000375530
        • Wild R.A.
        • Carmina E.
        • Diamanti-Kandarakis E.
        • et al.
        Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society.
        J Clin Endocrinol Metab. 2010; 95: 2038-2049
        • Pasch L.
        • He S.Y.
        • 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: 783-788
        • Ekback M.P.
        • Lindberg M.
        • Benzein E.
        • et al.
        Health-related quality of life, depression and anxiety correlate with the degree of hirsutism.
        Dermatology. 2013; 227: 278-284
        • Drosdzol A.
        • Skrzypulec V.
        • Plinta R.
        Quality of life, mental health and self-esteem in hirsute adolescent females.
        J Psychosom Obstet Gynaecol. 2010; 31: 168-175
        • Claman P.
        Hirsutism in women: evaluation and treatment.
        Hosp Med. 1995; : 17-29
        • Richards R.N.
        • Meharg G.E.
        Electrolysis: observations from 13 years and 140,000 hours of experience.
        J Am Acad Dermatol. 1995; 33: 662-666
        • Sommer S.
        • Render C.
        • Burd R.
        • et al.
        Ruby laser treatment for hirsutism: clinical response and patient tolerance.
        Br J Dermatol. 1998; 138: 1009-1014
        • Wheeland R.G.
        Laser-assisted hair removal.
        Dermatol Clin. 1997; 15: 469-477
        • Somani N.
        • Turvy D.
        Hirsutism: an evidence-based treatment update.
        Am J Clin Dermatol. 2014; 15: 247-266
        • Haedersdal M.
        • Gotzsche P.C.
        Laser and photoepilation for unwanted hair growth.
        Cochrane Database Syst Rev. 2006; : CD004684
        • Alexis A.F.
        Lasers and light-based therapies in ethnic skin: treatment options and recommendations for Fitzpatrick skin types V and VI.
        Br J Dermatol. 2013; 169: 91-97
        • Ismail S.A.
        Long-pulsed nd:YAG laser vs. intense pulsed light for hair removal in dark skin: a randomized controlled trial.
        Br J Dermatol. 2012; 166: 317-321
        • Puri N.
        Comparative study of diode laser versus neodymium-yttrium aluminum: garnet laser versus intense pulsed light for the treatment of hirsutism.
        J Cutan Aesthet Surg. 2015; 8: 97-101
        • Balfour J.A.
        • McClellan K.
        Topical eflornithine.
        Am J Clin Dermatol. 2001; 2 (discussion 202): 197-201
        • Jackson J.
        • Caro J.J.
        • Caro G.
        • et al.
        The effect of eflornithine 13.9% cream on the bother and discomfort due to hirsutism.
        Int J Dermatol. 2007; 46: 976-981
        • Hamzavi I.
        • Tan E.
        • Shapiro J.
        • et al.
        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: 54-59
        • Vissing A.C.
        • Taudorf E.H.
        • Haak C.S.
        • et al.
        Adjuvant eflornithine to maintain IPL-induced hair reduction in women with facial hirsutism: a randomized controlled trial.
        J Eur Acad Dermatol Venereol. 2016; 30: 314-319
        • van der Vange N.
        • Blankenstein M.A.
        • Kloosterboer H.J.
        • et al.
        Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone.
        Contraception. 1990; 41: 345-352
        • van Zuuren E.J.
        • Fedorowicz Z.
        • Carter B.
        • et al.
        Interventions for hirsutism (excluding laser and photoepilation therapy alone).
        Cochrane Database Syst Rev. 2015; : CD010334
        • Sahin Y.
        • Dilber S.
        • Kelestimur F.
        Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of hirsutism.
        Fertil Steril. 2001; 75: 496-500
        • Hugon-Rodin J.
        • Gompel A.
        • Plu-Bureau G.
        Epidemiology of hormonal contraceptives-related venous thromboembolism.
        Eur J Endocrinol. 2014; 171: R221-R230
        • Bitzer J.
        • Amy J.J.
        • Beerthuizen R.
        • et al.
        Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism.
        Eur J Contracept Reprod Health Care. 2013; 18: 143-147
        • Dinger J.
        • Bardenheuer K.
        • Heinemann K.
        Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: final results from the International Active Surveillance Study of Women Taking Oral Contraceptives.
        Contraception. 2014; 89: 253-263
        • Dinger J.C.
        • Heinemann L.A.
        • Kuhl-Habich D.
        The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation.
        Contraception. 2007; 75: 344-354
        • Okoroh E.M.
        • Boulet S.L.
        • George M.G.
        • et al.
        Assessing the intersection of cardiovascular disease, venous thromboembolism, and polycystic ovary syndrome.
        Thromb Res. 2015; 136: 1165-1168
        • Bird S.T.
        • Hartzema A.G.
        • Brophy J.M.
        • et al.
        Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis.
        CMAJ. 2013; 185: E115-E120
        • Okoroh E.M.
        • Hooper W.C.
        • Atrash H.K.
        • et al.
        Is polycystic ovary syndrome another risk factor for venous thromboembolism? United States, 2003-2008.
        Am J Obstet Gynecol. 2012; 207: 377.e1-377.e8
        • Rittmaster R.S.
        Medical treatment of androgen dependent hirsutism.
        J Clin Endocrinol Metab. 1995; 80: 2559-2563
        • Kelekci K.H.
        • Kelekci S.
        • Yengel I.
        • et al.
        Cyproterone acetate or drospirenone containing combined oral contraceptives plus spironolactone or cyproterone acetate for hirsutism: randomized comparison of three regimens.
        J Dermatolog Treat. 2012; 23: 177-183
        • Swiglo B.A.
        • Cosma M.
        • Flynn D.N.
        • 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: 1153-1160
        • 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
        • 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
        • 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
        • Erenus M.
        • Yucelten D.
        • Gurbuz O.
        • et al.
        Comparison of spironolactone-oral contraceptive versus cyproterone acetate-estrogen regimens in the treatment of hirsutism.
        Fertil Steril. 1996; 66: 216-219
        • Tremblay R.R.
        Treatment of hirsutism with spironolactone.
        Clin Endocrinol Metab. 1986; 15: 363-371
        • Barth J.H.
        • Cherry C.A.
        • Wojnarowska F.
        • et al.
        Cyproterone acetate for severe hirsutism: results of a double-blind dose-ranging study.
        Clin Endocrinol (Oxf). 1991; 35: 5-10
        • Belisle S.
        • Love E.J.
        Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study.
        Fertil Steril. 1986; 46: 1015-1020
        • Van der Spuy Z.M.
        • le Roux P.A.
        Cyproterone acetate for hirsutism.
        Cochrane Database Syst Rev. 2003; : CD001125
        • Heinemann L.A.
        • Will-Shahab L.
        • van Kesteren P.
        • et al.
        Safety of cyproterone acetate: report of active surveillance.
        Pharmacoepidemiol Drug Saf. 1997; 6: 169-178
        • Moghetti P.
        • Castello R.
        • Magnani C.M.
        • et al.
        Clinical and hormonal effects of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism.
        J Clin Endocrinol Metab. 1994; 79: 1115-1121
        • Fruzzetti F.
        • de Lorenzo D.
        • Parrini D.
        • et al.
        Effects of finasteride, a 5 alpha-reductase inhibitor, on circulating androgens and gonadotropin secretion in hirsute women.
        J Clin Endocrinol Metab. 1994; 79: 831-835
        • Sahin Y.
        • Bayram F.
        • Kelestimur F.
        • et al.
        Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism.
        J Endocrinol Invest. 1998; 21: 348-352
        • Cusan L.
        • Dupont A.
        • Gomez J.L.
        • et al.
        Comparison of flutamide and spironolactone in the treatment of hirsutism: a randomized controlled trial.
        Fertil Steril. 1994; 61: 281-287
        • 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 Metab. 1999; 84: 1304-1310
        • 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.
        Fertil Steril. 1996; 66: 734-740
        • Muderris II,
        • Bayram F.
        • Sahin Y.
        • et al.
        A comparison between two doses of flutamide (250 mg/d and 500 mg/d) in the treatment of hirsutism.
        Fertil Steril. 1997; 68: 644-647
        • Carmina E.
        • Lobo R.A.
        Peripheral androgen blockade versus glandular androgen suppression in the treatment of hirsutism.
        Obstet Gynecol. 1991; 78: 845-849
        • Rittmaster R.S.
        • Givner M.L.
        Effect of daily and alternate day low dose prednisone on serum cortisol and adrenal androgens in hirsute women.
        J Clin Endocrinol Metab. 1988; 67: 400-403
        • Carmina E.
        • Lobo R.A.
        Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as high dose cyproterone acetate but results in a longer remission.
        Hum Reprod. 1997; 12: 663-666
        • Heiner J.S.
        • Greendale G.A.
        • Kawakami A.K.
        • et al.
        Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism.
        J Clin Endocrinol Metab. 1995; 80: 3412-3418
        • Acien P.
        • Mauri M.
        • Gutierrez M.
        Clinical and hormonal effects of the combination gonadotrophin-releasing hormone agonist plus oral contraceptive pills containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone on polycystic ovarian disease-related hyperandrogenisms.
        Hum Reprod. 1997; 12: 423-429
        • Morin-Papunen L.C.
        • Koivunen R.M.
        • Ruokonen A.
        • et al.
        Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome.
        Fertil Steril. 1998; 69: 691-696
        • Cosma M.
        • Swiglo B.A.
        • Flynn D.N.
        • 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: 1135-1142
        • Anttila L.
        • Koskinen P.
        • Kaihola H.L.
        • et al.
        Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.
        Fertil Steril. 1992; 58: 697-702
        • Segall-Gutierrez P.
        • Du J.
        • Niu C.
        • et al.
        Effect of subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) on serum androgen markers in normal-weight, obese, and extremely obese women.
        Contraception. 2012; 86: 739-745
        • Coulam C.B.
        • Annegers J.F.
        • Kranz J.S.
        Chronic anovulation syndrome and associated neoplasia.
        Obstet Gynecol. 1983; 61: 403-407
        • Vause T.D.
        • Cheung A.P.
        • Sierra S.
        • et al.
        Ovulation induction in polycystic ovary syndrome: No. 242, May 2010.
        Int J Gynaecol Obstet. 2010; 111: 95-100