Hirsutism in Women DAVID BODE, CPT, MC, USA, Brooke Army Medical Center, Fort Sam Houston, Texas DEAN A. SEEHUSEN, LTC, MC, USA, Fort Belvoir Community Hospital, Fort Belvoir, Virginia DREW BAIRD, CPT, MC, USA, Carl R. Darnall Army Medical Center, Fort Hood, Texas

Hirsutism is excess terminal that commonly appears in a male pattern in women. Although hirsutism is generally associated with hyperandrogenemia, one-half of women with mild symptoms have normal levels. The most common cause of hirsutism is polycystic syndrome, accounting for three out of every four cases. Many medi- cations can also cause hirsutism. In patients whose hirsutism is not related to use, evaluation is focused on testing for endocrinopathies and , such as polycystic ovary syndrome, adrenal hyperplasia, thyroid dysfunction, Cushing syndrome, and androgen-secreting tumors. Symptoms and findings suggestive of include rapid onset of symptoms, signs of , and a palpable abdominal or pelvic mass. Patients without these findings who have mild symptoms and normal menses can be treated empirically. For patients with moder- ate or severe symptoms, an early morning total level should be obtained, and if moderately elevated, it should be followed by a plasma free testosterone level. A total testosterone level greater than 200 ng per dL (6.94 nmol per L) should prompt evaluation for an androgen-secreting tumor. Further workup is guided by history and physical examination, and may include thyroid function tests, level, 17-hydroxyprogesterone level, and corticotro- pin stimulation test. Treatment includes and pharmacologic measures. is effective but needs to be repeated often. Evidence for the effectiveness of electrolysis and therapy is limited. In patients who are not planning a , first-line pharmacologic treatment should include oral contraceptives. Topical agents, such as , may also be used. Treatment response should be monitored for at least six months before making adjust- ments. (Am Fam . 2012;85(4):373-380. Copyright © 2012 American Academy of Family .) ▲ Patient information: irsutism is defined as excess term “patient-important hirsutism” to indi- A handout on this topic that commonly cate symptoms significant enough to cause is available at http:// familydoctor.org/210.xml. appears in a male pattern in the patient distress, regardless of the degree women. It is generally associ- of physical findings.1,7 H ated with hyperandrogenemia.1 Hirsutism occurs in approximately 7 percent of women Pathogenesis and has an estimated economic burden in , including testosterone, dihy- the of more than $600 mil- drotestosterone, and their prohormones lion annually.2,3 Hirsutism should be dis- sulfate and andro- tinguished from , which is stenedione, are the key factors in the growth generalized excessive hair growth not caused and development of sexual hair. Androgens by androgen excess. Hypertrichosis may be act on -specific areas of the body, convert- congenital or caused by metabolic disorders ing small, straight, fair vellus to larger, such as thyroid dysfunction, anorexia ner- curlier, and darker terminal hairs.8 Men vosa, and .4 have higher androgen levels during and after Hirsutism is often classified in terms of , and thus a greater degree of termi- the distribution and degree of hair growth, nal hair development in sex-specific areas such as through pictorial scales. The most compared with women. Hirsutism develops widely recognized scoring method is the in women when there is excessive growth of Ferriman-Gallwey scale (Figure 1).5,6 This terminal hair in these areas, typically due to scale is limited by its subjective nature and androgen excess.9 its failure to account for all androgenic areas In addition to hirsutism, hyperandro- (e.g., , ), focal hirsutism, genemia can manifest as , menstrual ongoing use of cosmetic measures, or effect dysfunction, or alopecia, or could be asymp- on patient well-being. Given these limita- tomatic.1 The severity of hirsutism is vari- tions, some experts recommend use of the able at a given level of androgen excess, Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2012 American Academy of Family Physicians. For the private, noncom- Februarymercial 15,use 2012of one ◆ individual Volume user85, ofNumber the Web 4 site. All other rights reserved.www.aafp.org/afp Contact [email protected] for copyright questionsAmerican and/or Family permission Physician requests. 373 SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence Clinical recommendation rating References

Any patient with rapid onset of hirsutism, C 1, 18-20 suggesting that hirsutism is also related to obvious signs of virilization, or a palpable the sensitivity of hair follicles to androgens.10 abdominal or pelvic mass should undergo a thorough workup for a possible androgen-secreting tumor. Causes Women with mild hirsutism and normal C 1, 19 Table 1 outlines the causes of hirsutism and menses do not require laboratory workup their diagnostic clues.1,9,11,12 Multiple medi- and can be treated empirically. cations have been associated with hirsutism First-line pharmacologic treatment of C 1, 19 and/or hypertrichosis and should also be hirsutism in women not trying to conceive considered in the evaluation of excessive hair should include oral contraceptives. growth (Table 2).13 A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited- quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual POLYCYSTIC OVARY SYNDROME practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml. The most common cause of hirsutism is polycystic ovary syndrome (PCOS), which

1 2 3 4 1 2 3 4

1 2 3 4

1 2 3 4

1 2 3 4

1 2 3 4

1 2 3 4

1 2 3 4

1 2 3 4 ILLUSTRATION BY RENEE CANNON RENEE BY ILLUSTRATION Figure 1. The Ferriman-Gallwey scale for hirsutism. A score of 1 to 4 is given for nine areas of the body. A total score less than 8 is considered normal, a score of 8 to 15 indicates mild hirsutism, and a score greater than 15 indicates moderate or severe hirsutism. A score of 0 indicates absence of terminal hair. Information from references 5 and 6.

374 American Family Physician www.aafp.org/afp Volume 85, Number 4 ◆ February 15, 2012 Table 1. Causes of Hirsutism and Their Diagnostic Clues

Percentage of Diagnosis hirsutism cases Distinguishing historical and clinical clues

Polycystic ovary 72 to 82 Irregular menses syndrome Normal to mildly elevated androgen levels Polycystic on ultrasonography Central Infertility resistance Acanthosis nigricans Idiopathic 6 to 15 Normal menses hyperandrogenemia Normal ovaries on ultrasonography Elevated androgen levels No other explainable cause Idiopathic hirsutism 4 to 7 Normal menses, androgen levels, and ovaries on ultrasonography No other explainable cause Adrenal hyperplasia 2 to 4 Family history of congenital adrenal hyperplasia High-risk ethnic group (e.g., Ashkenazi Jews [1 in 27], Hispanic persons [1 in 40], Slavs [1 in 50]) Classic form: ambiguous genitalia at birth Nonclassic, late-onset form: menstrual dysfunction, oligoanovulation, infertility Elevated 17-hydroxyprogesterone level before and after corticotropin stimulation test Androgen-secreting 0.2 Rapid onset of hirsutism tumors Progression of hirsutism despite treatment Virilization (e.g., clitoromegaly, increased muscle mass, loss of female body contour) Palpable abdominal or pelvic mass Early morning total testosterone level greater than 200 ng per dL (6.94 nmol per L) Iatrogenic hirsutism Uncommon (exact Medication history (see Table 2) percentage not well-defined in the literature) Rare to present with Frontal bossing, increased and size, isolated hirsutism mandibular enlargement, coarse features, , deepened voice Elevated serum insulin-like growth factor 1 Cushing syndrome Rare to present with Central obesity, moon facies, purple striae, isolated hirsutism proximal muscle weakness, acne , impaired glucose tolerance Elevated 24-hour urine free cortisol level Hyperprolactinemia Rare to present with Galactorrhea, amenorrhea, infertility isolated hirsutism Elevated prolactin level Thyroid dysfunction Rare to present with : fatigue, cold intolerance, dry isolated hirsutism skin, , myxedema, weight gain, difficulty concentrating, irregular menses : hyperactivity, heat intolerance, moist skin, palpitations, oligomenorrhea, goiter, exophthalmos Abnormal thyroid function tests

Information from references 1, 9, 11, and 12.

February 15, 2012 ◆ Volume 85, Number 4 www.aafp.org/afp American Family Physician 375 Table 2. Common Associated with Hirsutism and/or Hypertrichosis

Hirsutism Hirsutism (continued) Aripiprazole (Abilify) Paroxetine (Paxil) ADRENAL HYPERPLASIA Bimatoprost (Lumigan)* Pregabalin (Lyrica) Less than 5 percent of patients with hirsutism Bupropion (Wellbutrin) Progestins have adrenal hyperplasia, a defect in adrenal Carbamazepine (Tegretol) Selegiline (Eldepryl) cortisol synthesis that diverts precursors Clonazepam (Klonopin) (Prograf)* into the androgen synthesis pathway. Classic Corticosteroids (systemic) Testosterones adrenal hyperplasia is diagnosed at birth by Cyclosporine (Sandimmune) Tiagabine (Gabitril) ambiguous genitalia, but nonclassic adrenal Dantrolene (Dantrium) Trazodone hyperplasia can remain asymptomatic until Diazoxide (Proglycem) Venlafaxine (Effexor) after puberty, when women develop men- Donepezil (Aricept) Zonisamide (Zonegran) strual dysfunction and anovulation.17 Hypertrichosis ANDROGEN-SECRETING TUMORS Eszopiclone (Lunesta) (Soriatane) Fluoxetine (Prozac) (Finacea) Androgen-secreting tumors are rare in Interferon alfa* Cetirizine (Zyrtec) women with hirsutism, comprising 0.2 per- Citalopram (Celexa) cent of cases in two studies of women pre- Lamotrigine (Lamictal) Corticosteroids (topical) senting with clinical hyperandrogenemia.9,11 Leuprolide (Lupron) Cyclosporine* Neoplasms may be adrenal or ovarian in ori- Mycophenolate (Cellcept)* implant (Implanon) gin, and often cause large elevations in andro- Olanzapine (Zyprexa) (Dilantin) gen level. More than one-half are malignant. Rapid onset of hirsutism, virilization, or a *—Medications with an associated incidence of hirsutism and/or hypertrichosis of at palpable abdominal or pelvic mass all raise least 3 percent. suspicion for an androgen-secreting tumor.1 Information from reference 13. OTHER CAUSES Several other endocrinopathies can present accounts for 72 to 82 percent of hirsutism with hirsutism but often have more distinc- cases.9,11 PCOS is defined by the presence tive presentations. These include acromeg- of at least two of the following three signs: aly, Cushing syndrome, hyperprolactinemia, menstrual dysfunction, clinical or bio- and thyroid dysfunction.1 chemical evidence of hyperandrogenemia, and polycystic ovaries on ultrasonogra- Evaluation phy. Other characteristics of PCOS include Figure 2 provides a suggested approach to obesity, infertility, and . evaluating hirsutism.1,18 Insulin resistance and The medical history should include a stimulate the adrenal glands and ovaries to medication and supplement review. The produce more androgens. Hyperinsulinemia patient should be asked if the excess hair also inhibits the hepatic synthesis of sex growth began at puberty or after, and if its –binding globulin, which binds onset was rapid. A menstrual and repro- testosterone and makes it inactive.14 ductive history should also be obtained, as well as the hair patterns of family members IDIOPATHIC (if possible) because idiopathic hirsutism Hirsutism is caused by idiopathic hyperand­ is often familial.18 Patients should be asked rogenemia in less than 20 percent of cases, and if they have noticed changes in their voice, is characterized by normal ovulatory cycles , , skin, or muscle mass. It and no other identifiable cause of elevated is also important to ask what hair removal androgen levels.15 Idiopathic hirsutism, in measures have already been tried. which androgen levels are normal, accounts Physical examination should begin with for 4 to 7 percent of cases and is a diagnosis determination of the distribution and degree of exclusion.9,11 One-half of all women with of hair growth using a scoring method such mild hirsutism (a Ferriman-Gallwey score of as the Ferriman-Gallwey scale (Figure 1).5,6 8 to 15) have idiopathic hirsutism.16 The patient should be evaluated for signs of

376 American Family Physician www.aafp.org/afp Volume 85, Number 4 ◆ February 15, 2012 Evaluation of Hirsutism in Women

Chief problem of excess

History and physical examination, including pelvic examination

Normal variant, hypertrichosis, Moderate or severe Risk of androgen-secreting mild hirsutism (Ferriman- hirsutism (Ferriman- tumor: virilization, rapid Gallwey score 8 to 15), Gallwey score >15), risk of onset of hirsutism, palpable patient-important hirsutism polycystic ovary syndrome abdominal or pelvic mass

6-month trial of therapy; Progression Early morning total > 200 ng per dL Full hormonal discontinuation of potentially of symptoms testosterone level (6.94 nmol per L) workup, imaging as contributing medications obtained at a indicated, consider specialty laboratory surgical exploration

Good results: continue therapy ≤ 200 ng per dL

Thyroid function tests, prolactin level, 17-hydroxyprogesterone level; consider testing for Cushing syndrome

17-hydroxyprogesterone Abnormal thyroid Elevated prolactin level Testosterone mildly Normal workup: level > 200 ng per dL function tests elevated and irregular idiopathic (6.1 nmol per L) menses: polycystic hirsutism likely Image ovary syndrome likely Treat thyroid Corticotropin disorder stimulation test Trial of therapy, monitor for response

≤ 1,000 ng per dL indicates > 1,000 ng per dL indicates a heterozygote carrier of late-onset adrenal hyperplasia/ 21-hydroxylase deficiency 21-hydroxylase deficiency

Figure 2. A suggested approach to the evaluation of hirsutism. Information from references 1 and 18. virilization, including clitoromegaly, acne, palpable abdominal or pelvic mass should deep voice, balding, or loss of typical female undergo a thorough workup for a possible body contours. An abdominal and bimanual androgen-secreting tumor.1,18-20 In contrast, examination should be performed to iden- patients with mild hirsutism and normal tify palpable tumors. A skin examination menses do not require laboratory workup and should check for acne, striae, or acantho- can safely be started on empiric therapy.1,19 If sis nigricans. The patient’s breasts should the condition does not respond to therapy or be examined for galactorrhea. Physicians progresses, further testing is warranted.19 should look for other typical signs of endo- In patients with moderate or severe hir- crinopathies, such as Cushing syndrome or sutism or a history of possible PCOS, an thyroid dysfunction. early morning testosterone level should be If possible, androgenic medications should obtained. Testosterone testing is inherently be stopped. Any patient with rapid onset of difficult, and specialty laboratories that hirsutism, obvious signs of virilization, or a employ proficiency testing using samples

February 15, 2012 ◆ Volume 85, Number 4 www.aafp.org/afp American Family Physician 377 Hirsutism

with known concentrations should be used HAIR REMOVAL METHODS if possible.20 A total testosterone level greater Several methods of direct temporary hair than 200 ng per dL (6.94 nmol per L) is removal are available. Shaving is fast, safe, indicative of an androgen-secreting tumor. and effective, but needs to be repeated often. Plasma free testosterone is 50 percent more Hair regrowth after shaving appears to be sensitive than total testosterone, but because coarser, because the tip is blunt rather than this testing is expensive and not widely avail- tapered. Chemical depilation can be used to able, it should be considered only if total tes- dissolve hairs, but can cause a reactive der- tosterone levels are moderately elevated.19 matitis.1 Epilation methods, such as Routine testing of other androgens, such or , remove hairs down to above the as dehydroepiandrosterone sulfate, is not bulb; however, in addition to the discomfort recommended, because mild elevations are of the procedure, scarring, , and common and have limited predictive value may occur.1 in the setting of normal testosterone levels.1 More permanent methods of hair removal Further workup should include thy- include electrolysis, laser epilation, and pho- roid function tests, and prolactin and toepilation. Electrolysis, either galvanic or 17-hydroxyprogesterone levels. A urine thermal, is painful and time-consuming free cortisol level, dexamethasone suppres- because each needs to be indi- sion test, or midnight cortisol level can be vidually targeted. For this reason, electroly- included if Cushing syndrome is suspected.21 sis is a good option only for treating small If the 17-hydroxyprogesterone level is greater areas of skin.1 than 200 ng per dL (6.1 nmol per L), a cor- Laser therapy is less painful and faster ticotropin stimulation test should be per- than electrolysis, and is widely believed to formed to evaluate for adrenal hyperplasia.18 be more effective; however, it is also more A patient with idiopathic hirsutism or a mild expensive. A recent Cochrane review of hair to moderately elevated testosterone level and removal methods found little evidence of an anovulatory history suggestive of PCOS their effectiveness.24 Alexandrite and diode should be treated appropriately and moni- reduced hair by approximately 50 per- tored for improvement.22 cent up to six months after treatment. Less Little research has been done regarding evidence is available for short-term effects hirsutism occurring outside of the peri- of pulsed light, neodymium: yttrium- pubertal period. The onset of hirsutism in aluminum-garnet (Nd:YAG), and ruby young children and postmenopausal women lasers, and none of these treatments have warrants further evaluation and subspecialty well-documented long-term outcomes.24 referral given the increased concern for neo- Laser epilation and photoepilation work best plastic or secondary endocrine sources. in women with light skin because less energy is required per pulse. Hyperpigmentation is Treatment a common adverse effect. Hair regrowth can Treatment of hirsutism should be guided by occur in women with hyperandrogenemia the severity of the condition and the amount through conversion of remaining of distress it is causing the patient. Addition- follicles into terminal hair.19 ally, the reproductive status of the patient and potential adverse effects should be fac- PHARMACOLOGIC METHODS tored into treatment decisions. Currently, Table 3 lists medications commonly used to there are no pharmacologic options indi- treat hirsutism.1,18,19,25 cated for pregnant women. Women desiring Combination oral contraceptives reduce fertility may consider cosmetic hair removal. serum free androgen levels by increasing sex Women who are obese should be encour- hormone–binding globulin and inhibiting aged to lose weight because obesity increases ovarian androgen production. The Endocrine serum androgen levels and reduces the effec- Society recommends oral contraceptives as tiveness of medical treatment.23 the first-line medication for women not trying

378 American Family Physician www.aafp.org/afp Volume 85, Number 4 ◆ February 15, 2012 Table 3. Medications Commonly Used for Treatment of Hirsutism

FDA pregnancy Medication Dosage Adverse effects Comments category

Oral One tablet daily Gastrointestinal upset, Recommended first-line agents; X contraceptives headache formulations containing , (various) , or are preferred 500 to 1,000 mg Gastrointestinal upset Useful for treating polycystic ovary B (Glucophage) twice daily syndrome, but no data to support primary use for hirsutism 100 to 200 mg Hyperkalemia, irregular Risk of pseudohermaphroditism in male D (Aldactone) daily menses if used during pregnancy 2.5 mg daily — X (Propecia) 5 to 10 mg daily Weight gain, bone density Indicated in congenital adrenal hyperplasia C () loss, adrenal suppression Leuprolide 3.75 to 7.5 mg Hot flashes, atrophic Consider adding back hormone therapy; X (Lupron) intramuscularly vaginitis, bone density expensive monthly loss 400 mg daily Dry skin, headache, Typically used only after failure of other C hepatotoxicity therapies Eflornithine Apply topically Acne, , burning FDA approval is only for use for unwanted C (Vaniqa) twice daily

FDA = U.S. Food and Drug Administration. Information from references 1, 18, 19, and 25.

to conceive.1 The few trials of oral contracep- Eflornithine (Vaniqa) is a topical agent tives have shown a reduction in hirsutism that reduces hair growth through inhibition over placebo or no therapy. Oral contracep- of decarboxylase. When used for tives containing the progestins norgestimate, excess facial hair, results are noticed in about desogestrel, or drospirenone are preferred eight weeks. Eflornithine can be used alone because of their lower androgenic effects and/ or in conjunction with other therapies. Hair or their androgen blocking effects.1,23,26 growth resumes after discontinuation.1,18 The spironolactone (Alda- Other medications may be used in special ctone), finasteride (Propecia), , cases. -releasing hormone ago- and (not available in the United nists are reserved for use in severe cases that States) have been shown to be effective treat- have not responded to other therapies.1 Glu- ments for hirsutism.1,23,27 Because of their cocorticoids are sometimes used in cases of teratogenic effects, they should be used only nonclassic congenital adrenal hyperplasia.19 in women who cannot conceive or who are Ketoconazole has been suggested for patients using . The Endocrine Society in whom other therapies have failed.18 recommends against the use of flutamide Any therapy for hirsutism should be con- because of the possibility of liver failure.1 tinued for at least six months (the average Insulin-lowering agents, such as met- cycle of a hair follicle) before determin- formin (Glucophage) and pioglitazone ing its effectiveness. If response at that time (Actos), have been suggested as alternative is inadequate, options include switching therapies. Although patients with PCOS are agents or using . There often treated with insulin-lowering agents is little evidence to suggest that combination to improve their insulin sensitivity and therapy is superior to monotherapy.1 fertility, the evidence suggests that these medications provide little or no benefit for Data Sources: A PubMed search was completed in Clini- cal Queries using the key terms hirsutism, hypertrichosis, hirsutism symptoms and should not be used hyperandrogenemia/, hair removal, as a primary treatment for hirsutism.1,25,26 congenital adrenal hyperplasia, and polycystic ovarian

February 15, 2012 ◆ Volume 85, Number 4 www.aafp.org/afp American Family Physician 379 Hirsutism

syndrome. The search included meta-analyses, random- Extensive clinical experience: relative prevalence of ized controlled trials, clinical trials, and reviews. Also different androgen excess disorders in 950 women searched were the Cochrane database, Essential Evidence referred because of clinical hyperandrogenism. J Clin Plus, and the reference sections of cited articles. Search Endocrinol Metab. 2006;91(1):2-6. date: August 1, 2010. 10. Karrer-Voegeli S, Rey F, Reymond MJ, Meuwly JY, Gail- lard RC, Gomez F. Androgen dependence of hirsutism, The views expressed in this article are those of the acne, and alopecia in women: retrospective analysis authors and do not reflect the policy or position of the of 228 patients investigated for hyperandrogenism. U.S. Army Medical Department, Department of Army, Medicine (Baltimore). 2009;88(1):32-45. Department of Defense, or the U.S. Government. 11. Azziz R, Sanchez LA, Knochenhauer ES, et al. Andro- gen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004; The Authors 89(2):453-462. DAVID BODE, CPT, MC, USA, is a fellow in the Department 12. Fauci AS, et al., eds. 2008. Harrison’s Principles of Inter- of at Brooke Army Medical Center, nal Medicine. 17th ed. New York, NY: McGraw-Hill Fort Sam Houston, Tex. Medical; 2008. 13. Physicians’ Desk Reference Web site. http://www.pdr. DEAN A. SEEHUSEN, LTC, MC, USA, is the program director net. Accessed April 13, 2011. of the family medicine residency program at Fort Belvoir 14. Codner E, Escobar-Morreale HF. Clinical review: Hyper- Community Hospital, Va. At the time this article was writ- androgenism and polycystic ovary syndrome in women ten, he was chief of family medicine service at Evans Army with type 1 mellitus. J Clin Endocrinol Metab. Community Hospital, Fort Carson, Colo. 2007;92(4):1209-1216. DREW BAIRD, CPT, MC, USA, is a staff physician at Carl R. 15. Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Darnall Army Medical Center, Fort Hood, Tex. Endocr Rev. 2000;21(4):347-362. 16. Reingold SB, Rosenfield RL. The relationship of mild hir- Address correspondence to David Bode, CPT, MC, sutism or acne in women to androgens. Arch Dermatol. USA, Brooke Army Medical Center, 3100 Schofield Rd., 1987;123(2):209-212. Bldg. 1179, Fort Sam Houston, TX 78234 (e-mail: dave. 17. New MI. Extensive clinical experience: nonclassical [email protected]). Reprints are not available from the 21-hydroxylase deficiency. J Clin Endocrinol Metab. authors. 2006;91(11):4205-4214. Author disclosure: No relevant financial affiliations to 18. Hunter MH, Carek PJ. Evaluation and treatment of women with hirsutism. Am Fam Physician. 2003;67(12): disclose. 2565-2572. 19. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med. REFERENCES 2005;353(24):2578-2588. 20. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position 1. Martin KA, Chang RJ, Ehrmann DA, et al. Evaluation statement: Utility, limitations, and pitfalls in measuring and treatment of hirsutism in premenopausal women: testosterone: an Endocrine Society position statement. an Endocrine Society clinical practice guideline. J Clin J Clin Endocrinol Metab. 2007;92(2):405-413. Endocrinol Metab. 2008;93 (4):1105-1120. 21. Elamin MB, Murad MH, Mullan R, et al. Accuracy of 2. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, diagnostic tests for Cushing’s syndrome: a systematic Yildiz BO. The prevalence and features of the polycys- review and metaanalyses. J Clin Endocrinol Metab. tic ovary syndrome in an unselected population. J Clin 2008;93(5):1553-1562. Endocrinol Metab. 2004;89(6):2745-2749. 22. Blume-Peytavi U, Atkin S, Shapiro J, et al.; Skin Acad- 3. Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health emy. European Consensus on the evaluation of women care-related economic burden of the polycystic ovary presenting with excessive hair growth. Eur J Dermatol. syndrome during the reproductive life span. J Clin Endo- 2009;19(6):597-602. crinol Metab. 2005;90(8):4650-4658. 23. Koulouri O, Conway GS. A of com- 4. Deplewski D, Rosenfield RL. Role of in pilo- monly used medical treatments for hirsutism in women. sebaceous unit development. Endocr Rev. 2000;21(4): Clin Endocrinol (Oxf). 2008;68(5):800-805. 363-392. 24. Haedersdal M, Gøtzsche PC. Laser and photoepilation 5. Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: for unwanted hair growth. Cochrane Database Syst Rev. implications, etiology, and management. Am J Obstet 2006;(4):CD004684. Gynecol. 1981;140(7):815-830. 25. Cosma M, Swiglo BA, Flynn DN, et al. Clinical review: 6. Ferriman D, Gallwey JD. Clinical assessment of body Insulin sensitizers for the treatment of hirsutism: a hair growth in women. J Clin Endocrinol Metab. 1961; systematic review and metaanalyses of randomized 21:1440-1447. controlled trials. J Clin Endocrinol Metab. 2008;93(4): 7. Yildiz BO, Bolour S, Woods K, Moore A, Azziz R. Visu- 1135-1142. ally scoring hirsutism. Hum Reprod Update. 2010; 26. Radosh L. Drug treatments for polycystic ovary syn- 16(1):51-64. drome. Am Fam Physician. 2009;79(8):671-676. 8. Rosenfield RL. Hirsutism and the variable response of 27. Brown J, Farquhar C, Lee O, Toomath R, Jepson RG. the pilosebaceous unit to androgen. J Investig Dermatol Spironolactone versus placebo or in combination with Symp Proc. 2005;10(3):205-208. steroids for hirsutism and/or acne. Cochrane Database 9. Carmina E, Rosato F, Jannì A, Rizzo M, Longo RA. Syst Rev. 2009;(2):CD000194.

380 American Family Physician www.aafp.org/afp Volume 85, Number 4 ◆ February 15, 2012