RxFiles Approach to the management of idiopathic hirsutism Milena Markovski MD CCFP Jill Hall ACPR Margaret Jin PharmD CDE CGP Tessa Laubscher MB ChB CCFP FCFP Loren Regier Case description • idiopathic hyperandrogenism—clinical and biochem- A 25-year-old white woman, A.G., presents to a ical hyperandrogenism but regular ovulatory cycles of family practice clinic seeking a levonorgestrel intra- normal length and normal ovary morphology; uterine device (IUD) for contraception. She has only • idiopathic hirsutism—hirsutism with normal andro- used condoms in the past, but A.G. recently became gen concentrations, ovulatory cycles, and ovary engaged and wants to avoid pregnancy for several morphology; more years while she completes her master’s degree. • nonclassic congenital adrenal hyperplasia; Her medical history is noncontributory; she has no • androgen-secreting tumours; and known allergies, is a non-smoker, uses no illicit • iatrogenic excess androgen. drugs, and has minimal alcohol intake. She takes a Hirsutism should be investigated and treated, not only daily multivitamin. to determine the underlying cause, but also because it Further history reveals that since puberty A.G. can negatively affect women’s psychological well-being. has experienced increased growth of facial hair. It A detailed history and physical examination are has caused considerable embarrassment for her, and most valuable when determining the cause of hirsutism. she is reluctant to discuss this issue with her physi- Methods for evaluation can be subjective and objective. cian. She also has mild acne, but has not tried any Visually scoring the body and facial terminal hair growth prescription therapies. She has heard from friends in specified body areas using the Ferriman-Gallwey that contraceptive pills cause increased growth score is more convenient and less expensive than of facial hair, and for this reason she has never more objective scoring with photographic evaluations, used any birth control medication. She has regular microscopic measurements, and weighing of shaved or monthly menses. plucked hair. The Ferriman-Gallwey tool scores 9 of the 11 androgen-sensitive hair growth areas on a scale of Examination 0 to 4 (for a maximum score of 36). A score of 8 to 15 Examination findings reveal that A.G. is a pleas- is considered mild hirsutism; a score above 15 is con- ant woman with appropriate affect. Measurements of sidered moderate to severe hirsutism.1 her vital signs are normal, with a blood pressure of Determination of serum androgen levels should be 110/84 mm Hg. Her body mass index is 26.8 kg/m2. the first step for establishing the cause of hirsutism. There is a moderate increase of dark facial hair in the Androgen contributes to the growth of sexual hair in chin area and on the upper lip. Her abdomen is soft and both sexes, as well as to the growth of facial and trunk nontender. She declines a pelvic examination because hair in women with hirsutism. The androgens found in she is menstruating. female serum include DHEA-S, DHEA, androstenedione, The patient is counseled about the causes of hirsut- testosterone, and dihydrotestosterone. The most active ism and agrees to further investigation. She is given a androgen, dihydrotestosterone, has low serum levels requisition for measurement of complete blood count; because it is synthesized in androgen target tissues. thyroid-stimulating hormone, fasting plasma glucose, For this reason, measurable circulating androgen levels and lipid levels; a renal panel; and free testosterone, might not reflect androgen activity in the hair follicles of luteinizing hormone, follicle-stimulating hormone, and women with hirsutism. Serum levels of DHEA-S and free dehydroepiandrosterone sulfate (DHEA-S) levels. A pel- testosterone are the most sensitive measurements of vic ultrasound is ordered as well, and A.G. is asked to androgen excess and are considered tumour markers.2,3 follow up in 2 weeks, at which time a suitable contra- If PCOS is suspected, a metabolic evaluation (meas- ceptive method will be discussed. urement of plasma glucose levels, waist circumference and body mass index, complete lipid profile, and blood Diagnostic approach pressure) is necessary to evaluate the patient’s risk of Androgen-excess disorders to consider in A.G.’s case metabolic and cardiovascular dysfunction. A common include the following: finding in PCOS is an increased luteinizing hormone to fol- • polycystic ovary syndrome (PCOS)—clinical or bio- licle-stimulating hormone ratio (> 2.5). Ultrasound might chemical hyperandrogenism in addition to ovarian aid in diagnosing PCOS, as well as nonclassic congenital dysfunction or polycystic ovary morphology; adrenal hyperplasia or androgen-secreting tumours. VOL 58: FEBRUARY • FÉVRIER 2012 | Canadian Family Physician • Le Médecin de famille canadien 173 RxFiles Management of hirsutism which the drug cannot be stopped, cosmetic measures An approach to treatment of hirsutism is outlined in might be of value to conceal or remove hair. Figure 1.1,2,4 Nonpharmacologic intervention. Targeted coun- Rule out potential drug-related causes. Drugs seling about self-image plays an important role in that can cause excessive hair growth (hirsutism or the treatment of hirsutism. Lifestyle modifications, hypertrichosis) include acetazolamide, anabolic ste- such as physical exercise and dietary advice, can roids (eg, danazol, nandrolone, stanozolol), andro- be recommended. Such modifications might be less genic progestogens or oral contraceptive pills (OCPs) effective for idiopathic hirsutism than for hirsutism containing progestogen (eg, norethindrone and caused by PCOS; however, they might also be worth- levonorgestrel found in first- and second-genera- while for cardiovascular protection.2 Cosmetic mea- tion OCPs), cyclosporine, diazoxide, glucocorticoids, sures, such as bleaching, plucking, shaving, waxing, drugs containing heavy metals, minoxidil, penicilla- chemical treatment, electrolysis, laser hair removal, mine, phenytoin, tamoxifen, and thyroxine.5,6 Drug- and intense pulsed light are usually effective in con- induced excessive hair growth is reversible upon trolling mild hirsutism, especially when terminal hair discontinuation of the offending agent. In cases in localizes in exposed areas such as the face. Figure 1. Management of idiopathic hirsutism HIRSUTISM Cosmetic procedures are a cornerstone of care; examples include laser surgery, Consider any drug-related causes shaving, plucking, bleaching, waxing, Initiate lifestyle modications chemical treatment, intense pulsed light, Consider cosmetic procedure options and electrolysis Seeking fertility Not seeking fertility Delay drug treatment Moderate to severe until delivery Mild hirsutism hirsutism Contraindication 1. Topical eornithine (8-wk OCP containing to OCP trial) (monotherapy or as an • Cyproterone adjunct to any hair removal • Drospirenone technique) • Neutral progestin (desogestral, norgestimate) 2. OCP containing Antiandrogen (with secure • Cyproterone PLUS antiandrogen contraception) • Drospirenone • Spironolactone • Spironolactone • Neutral progestin • Finasteride or cyproterone • Finasteride (desogestrel, norgestimate) • Cyproterone acetate • Flutamide Unsatisfactory result (at 6-12 mo) Metformin, while benecial in PCOS, is not effective for idiopathic hirsutism • Add oral agent to topical eflornithine • Add spironolactone, finasteride, or cyproterone to OCP OCP—oral contraceptive pill, PCOS—polycystic ovary syndrome. Adapted from Hirsutism.com,1 Escobar-Morreale et al,2 and Harrison et al.4 174 Canadian Family Physician • Le Médecin de famille canadien | VOL 58: FEBRUARY • FÉVRIER 2012 RxFiles Table 1. Medications used for idiopathic hirsutism1-8: Medications listed are contraindicated in pregnancy and require use of appropriate contraception. CLASS AND INGREDIENTS ROLE IN THERAPY EFFICACY DOSE (COST/30 D) • Eflornithine 13.9% • Monotherapy for mild cases of • Improvement noted at ≥ 8 wk; Topical; apply twice cream (Vaniqa) facial hirsutism or as adjunct to effect reverses 8 wk after daily, at least other therapies (complements discontinuation12-14 8 h apart antiandrogen, laser, or IPL • Used alone, treatment is successful ($64 per 30-g tube; CCI therapy) about 30% of the time (slows rate lasts about 3-5 mo for • Considered first-line in of hair growth); variable cosmetic upper lip and postmenopausal women significance14 4-6 wk for • Well tolerated: might cause rash, • Improves time to effect with laser lower face) burning, or tingling therapy (up to 95% successful)12 • EE with • Generalized hirsutism, for • Improvement noted at 3 mo; 1 tablet, orally, once drospirenone women not seeking fertility maximum effect at 9-12 mo daily ($17-$23) (Yasmin, Yaz) • All OCPs can help owing to • Yasmin: FGS 65%-70% lower at • EE with desogestrel estrogen’s effect on SHBG 6 mo and 80% lower at 12 mo18,19 (Marvelon, • Risk of VTE, although small, • Marvelon: FGS 40% lower at 6 mo Ortho-Cept, Linessa) increases with age (especially and 35% lower at 12 mo18 • EE with > 39 y) and possibly choice • Tri-Cyclen: no specific evidence norgestimate of OCP CPs O (Tri-Cyclen, -baseline risk: about 5/10 000 Tri-Cyclen LO, Cyclen) -with OCPs: 8-9/10 000 (up to • See full RxFiles 14/10 000) chart15 for other -possible increased risk with low-androgen OCP Yasmin, Yaz16,17 options • EE with • Mild hirsutism, severe acne • Diane-35: FGS 55% lower at 6 mo EE 35 µg with CPA cyproterone* • Risk of VTE, though small, might and 80% lower at 12 mo17,19 2 mg ($29)