PRACTICAL THERAPEUTICS Evaluation and Treatment of Women with Hirsutism MELISSA H. HUNTER, M.D., and PETER J. CAREK, M.D. Medical University of South Carolina, Charleston, South Carolina Hirsutism is a common disorder, often resulting from conditions that are not life- threatening. It may signal more serious clinical pathology, and clinical evaluation should differentiate benign causes from tumors or other conditions such as polycystic ovary syndrome, late-onset adrenal hyperplasia, and Cushing’s syndrome. Laboratory testing should be based on the patient’s history and physical findings, but screening for levels of serum testosterone and 17␣-hydroxyprogesterone is sufficient in most cases. Women with irregular menses and hirsutism should be screened for thyroid dys- function and prolactin disorders. Pharmacologic and/or nonpharmacologic treatments may be used. Advances in laser hair removal methods and topical hair growth retar- dants offer new options. The use of insulin-sensitizing agents may be useful in women with polycystic ovary syndrome. (Am Fam Physician 2003;67:2565-72. Copyright© 2003 American Academy of Family Physicians.) Members of various irsutism is a common disor- growth varies widely among women, and dis- family practice depart- der affecting up to 8 percent tinguishing normal variations of hair growth ments develop articles of women.1 It often results from hypertrichosis and true hirsutism is for “Practical Therapeu- tics.” This article is one from conditions that are not important. in a series coordinated life-threatening, such as With hirsutism, terminal hair grows from by the Department of Hchronic anovulation. Hirsutism is defined as androgen-sensitive pilosebaceous units.3,4 Family Medicine at the the presence of excessive terminal hair in While 60 to 80 percent of women with hir- Medical University of androgen-dependent areas of a woman’s sutism have increased levels of circulating South Carolina. Guest 2 editor of the series is body. The disorder is a sign of increased androgens, degrees of hirsutism correlate William J. Hueston, M.D. androgen action on hair follicles, from poorly with androgen levels.5 The ovary is the increased circulating levels of androgens major source of increased levels of testos- (endogenous or exogenous) or increased sen- terone in women who have hirsutism.6 Dehy- sitivity of hair follicles to normal levels of cir- droepiandrosterone sulfate (DHEAS) is an culating androgens. androgen that arises almost exclusively from Infrequently, hirsutism may signal more the adrenal gland but is an uncommon cause serious pathology, and clinical evaluation of hirsutism. Nearly all circulating testos- should differentiate benign causes from terone is bound to sex hormone binding glob- tumors or other conditions that require spe- ulin (SHBG) and albumin, with free testos- cific treatment. Most women who seek treat- terone being the most biologically active form. ment for hirsutism do so for cosmetic rea- When elevated insulin levels are present, sons, because excess body hair outside of SHBG levels decrease while free testosterone cultural norms can be very distressing. Hair levels increase. Hypertrichosis is defined as a diffuse in- crease in vellus hair growth and is not andro- Hirsutism is a sign of increased androgen action on hair gen dependent. Hypertrichosis may be con- genital (e.g., Hurler’s syndrome, trisomy 18 follicles, from increased circulating levels of androgens or syndrome, or fetal alcohol syndrome) or asso- increased sensitivity of hair follicles to normal levels of ciated with hypothyroidism, porphyrias, epi- circulating androgens. dermolysis bullosa, anorexia nervosa, malnu- trition, or dermatomyositis. It also may occur JUNE 15, 2003 / VOLUME 67, NUMBER 12 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 2565 TABLE 1 Medications That May Cause Hirsutism and/or Hypertrichosis Hirsutism Hypertrichosis Anabolic steroids Cyclosporine (Sandimmune) Danazol (Danocrine) Diazoxide (Hyperstat) after severe head injury, be present at sites of skin trauma, Metoclopramide Hydrocortisone 7 (Reglan) Minoxidil (Rogaine) or be drug induced (Table 1). Methyldopa Penicillamine (Cuprimine) (Aldomet) Phenytoin (Dilantin) Causes of Hirsutism Phenothiazines Psoralens (Oxsoralen) When evaluating hirsutism, it is important to remember Progestins Streptomycin that it is only one sign of hyperandrogenism. Other abnor- Reserpine (Serpasil) malities associated with excessive levels of androgen are Testosterone listed in Table 2.6,8 Increased androgen effect that results in hirsutism can be familial, idiopathic, or caused by excess Information from Leung AK, Robson WL. Hirsutism. Int J Derma- androgen secretion by the ovary (e.g., tumors, polycystic tol 1993;32:773-7. ovary syndrome [PCOS]), excess secretion of androgens by adrenal glands (e.g., congenital adrenal hyperplasia [CAH], Cushing’s syndrome, tumor), or exogenous phar- macologic sources of androgens. Table 38 outlines consid- TABLE 2 eration for these causes, along with laboratory findings. 9 Abnormalities Associated with Androgen Excess Idiopathic hirsutism is common and often familial. It is a diagnosis of exclusion and thought to be related to dis- Acne Glucose intolerance/insulin resistance orders in peripheral androgen activity. Onset occurs Alopecia Hirsutism shortly after puberty with slow progression. Patients with Android obesity Hypertension idiopathic hirsutism generally have normal menses and Cardiovascular disease Infertility normal levels of testosterone, 17␣-hydroxyprogesterone Dyslipidemia Menstrual dysfunction (17-OHP), and DHEAS. PCOS affects approximately 6 percent of women of Adapted with permission from Gilchrist VJ, Hecht BR. A practical reproductive age,10 and is represented by chronic anovula- approach to hirsutism. Am Fam Physician 1995;52:1837-46, with information from Speroff L, Glass RH, Kase NG, eds. Clinical gyne- tion and hyperandrogenemia, excluding other causes such cologic endocrinology and infertility. 6th ed. Baltimore: Lippincott as adult-onset CAH, hyperprolactinemia, and androgen- Williams & Wilkins, 1999:529-56. secreting tumors.11 Patients often report menstrual irregu- larities, infertility, obesity, and symptoms associated with androgen excess, and diagnosis usually is based on clinical rather than laboratory findings. Up to 70 percent of pa- tients with PCOS have signs of hyperandrogenism.12 The Authors CAH is a spectrum of inherited disorders of adrenal MELISSA H. HUNTER, M.D., is an associate professor in the Depart- steroidogenesis, with decreased cortisol production result- ment of Family Medicine, Medical University of South Carolina College ing in overproduction of androgenic steroids.13 Hirsutism, of Medicine, Charleston. She received her medical degree from the acne, menstrual disorders, and infertility may be present- Medical University of South Carolina College of Medicine, and com- pleted a residency in family medicine at McLeod Regional Medical ing symptoms during adolescence or adulthood. Center, Florence, S.C. Dr. Hunter also completed a faculty develop- Although rare, Cushing’s syndrome should be considered ment fellowship at the University of North Carolina at Chapel Hill in the differential diagnosis. It may be caused by increased School of Medicine. production of adrenocorticotropic hormone (ACTH) by the PETER J. CAREK, M.D., is an associate professor in the Department of pituitary, adrenal carcinoma/adenoma, or secretion of Family Medicine, Medical University of South Carolina College of Med- 14 icine. He received his medical degree from the Medical University of ectopic ACTH. Profound hirsutism is seen most commonly South Carolina College of Medicine, where he also served a residency in patients with macronodular hyperplasia, and clinical in family medicine. Dr. Carek completed a sports medicine fellowship signs of Cushing’s syndrome are usually quite apparent.14 and obtained a master’s degree in exercise physiology at the University of Tennessee, Memphis, College of Medicine. Hirsutism may result from use of exogenous pharmaco- logic agents, including danazol (Danocrine), anabolic Address correspondence to Melissa H. Hunter, M.D., University Family Medicine, 9298 Medical Plaza Dr., N. Charleston, SC 29406 [e-mail: steroids, and testosterone. Oral contraceptives (OCs) con- [email protected]]. Reprints are not available from the authors. taining levonorgestrel, norethindrone, and norgestrel tend 2566 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 67, NUMBER 12 / JUNE 15, 2003 TABLE 3 Causes of Hirsutism, Associated Laboratory Findings, and Recommended Additional Testing Diagnosis Testosterone 17-OHP LH/FSH Prolactin DHEAS Cortisol Additional testing Congenital Normal to Increased Normal/ Normal Normal Normal to ACTH stimulation may be adrenal increased normal to increased decreased necessary to make diagnosis. hyperplasia Polycystic Normal to Normal Normal to Normal to Normal to Normal Primarily a clinical diagnosis ovary increased increased increased increased Consider laboratory testing and syndrome LH and ultrasonography of ovaries to decreased rule out other disorders/tumors. to normal Consider screening lipids, glucose. FSH Ovarian Increased Normal Normal/ Normal Normal Normal Ultrasonography or CT to image tumor normal tumors Adrenal Increased Normal Normal/ Normal Increased Normal to Ultrasonography or CT to image tumor normal increased tumors Pharmacologic Normal Normal Normal/ Normal Normal Normal Withdrawal of offending agent agents normal recommended (exogenous)