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Table.  
Guideline Rating
Guideline Rating
1.
Martin  KA, Anderson  RR, Chang  RJ,  et al.  Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline  [published online March 7, 2018].  J Clin Endocrinol Metab. https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2018-00241.Google Scholar
2.
Pasch  L, He  SY, Huddleston  H,  et al.  Clinician vs self-ratings of hirsutism in patients with polycystic ovarian syndrome.  JAMA Dermatol. 2016;152(7):783-788.PubMedGoogle ScholarCrossref
3.
Martin  KA, Chang  RJ, Ehrmann  DA,  et al.  Evaluation and treatment of hirsutism in premenopausal women.  J Clin Endocrinol Metab. 2008;93(4):1105-1120.PubMedGoogle ScholarCrossref
4.
Rosner  W, Auchus  RJ, Azziz  R,  et al.  Utility, limitations, and pitfalls in measuring testosterone.  J Clin Endocrinol Metab. 2007;92(2):405-413.PubMedGoogle ScholarCrossref
5.
Sam  S, Ehrmann  DA.  Hormonal evaluation of hyperandrogenism in women.  JAMA. 2015;314(23):2557-2558.PubMedGoogle ScholarCrossref
6.
Stegeman  BH, de Bastos  M, Rosendaal  FR,  et al.  Different combined oral contraceptives and the risk of venous thrombosis.  BMJ. 2013;347:f5298.PubMedGoogle ScholarCrossref
JAMA Clinical Guidelines Synopsis
April 17, 2018

Evaluation and Treatment of Hirsutism in Premenopausal Women

Author Affiliations
  • 1University of Chicago, Chicago, Illinois
JAMA. 2018;319(15):1613-1614. doi:10.1001/jama.2018.2611
Box Section Ref ID

Guideline title Evaluation and Treatment of Hirsutism in Premenopausal Women

Developer Endocrine Society, Androgen Excess and Polycystic Ovary Syndrome Society, European Society of Endocrinology

Release date March 2018

Prior version February 5, 2008

Funding source Endocrine Society

Target population Premenopausal women with excess hair growth

Major recommendations

Diagnosis

  • Obtain a random serum total testosterone measurement to assess for androgen excess in all women with an abnormal hirsutism score (weak recommendation, low-quality evidence).

  • Obtain an early-morning 17-hydroxyprogesterone measurement in all women with elevated testosterone and in women with hirsutism who are at high risk of congenital adrenal hyperplasia (weak recommendation; low-quality evidence).

  • Do not measure androgen levels in women with normal menses and a normal hirsutism score (weak recommendation; low-quality evidence).

Pharmacologic treatment

  • Start with pharmacologic therapy and add direct hair removal methods for women with a normal hirsutism score but patient-important hirsutism despite shaving or plucking (weak recommendation; very low-quality evidence). In women who are not seeking pregnancy, oral contraceptive pills (OCPs) are recommended as initial therapy (weak recommendation; low-quality evidence).

  • Either OCPs or antiandrogens are acceptable initial therapies in women who are not sexually active, have undergone permanent sterilization, or are using long-acting reversible contraception (weak recommendation; very low-quality evidence).

  • Combination therapy with an antiandrogen is recommended if patient-important hirsutism persists despite 6 months of monotherapy with an OCP (weak recommendation; low-quality evidence).

Summary of the Clinical Problem

Hirsutism is defined as excessive terminal (coarse) hair growth in male androgen-dependent areas and is distinguished from hypertrichosis (generalized nonsexual excessive hair growth). Hirsutism affects 5% to 10% of women worldwide and can lead to significant emotional distress and expense1,2 involving medications, cosmetics, and hair removal procedures. Hirsutism is a clinical diagnosis based on the Ferriman-Gallwey (FG) score, which rates hair growth from 0 to 4 in 9 androgen-dependent areas. In the US general population, a normal score is less than 8; mild, 8-15; and severe, greater than 15.1 Polycystic ovary syndrome, associated with abnormally increased androgen levels, accounts for 75% to 80% of hirsutism.1 Another 5% to 20% of cases are due to idiopathic hirsutism, which is diagnosed in the absence of increased androgen levels.1 The remainder of cases (<5%) are due to rare but clinically important diagnoses that include nonclassic congenital adrenal hyperplasia, androgen-secreting tumors, and Cushing syndrome as well as medication adverse effects. Importantly, the current guideline recognizes and recommends treating patient-important hirsutism, defined as hair growth that causes distress in the absence of an abnormal hirsutism score.1,2

Characteristics of the Guideline Source

The commissioned task force was composed of 7 medical experts from endocrinology, reproductive endocrinology, dermatology, and obstetrics and gynecology, along with a methodologist. Committee members had no potential conflicts of interest in the previous year (Table).

Evidence Base

This guideline is an update of the 2008 guideline3 and addresses diagnosis, pharmacologic treatment, and direct hair removal methods. The guideline was based on 2 recent systematic reviews commissioned by the Endocrine Society designed to evaluate the efficacy and safety of different pharmacologic therapies for hirsutism. The GRADE approach was used to evaluate the strength and quality of supporting evidence.

The prior guideline recommended screening for elevated androgens with an FG score greater than 15. The updated guideline now recommends screening all women with a positive hirsutism score, defined as an FG score of 8 or greater in white and black women, 2 to 7 or greater in Asian women, depending on ethnicity, and 9 to 10 or greater in Hispanic and Middle Eastern women. When there is higher suspicion of elevated androgens (eg, oligomenorrhea or moderate to severe hirsutism with FG score >15), both morning total and free testosterone should also be measured. The guideline also recommends against screening women with a normal hirsutism score and normal menses because of the low probability of a positive result.

Optimized for higher levels in men, laboratory testosterone measurements have relatively low sensitivity and tend to be highly variable in women.4 The guideline recommends obtaining a random testosterone measurement followed by confirmatory total and free testosterone measurement in the early morning on days 4 to 10 of the menstrual cycle, when levels are the highest. More reliable assays use extraction and chromatography followed by mass spectroscopy or immunoassay to measure total testosterone. Additionally, sex hormone–binding globulin (SHBG) should be measured to obtain a calculated rather than direct measurement of free testosterone.4,5

Either an OCP, which increases SHBG, thereby lowering free testosterone, or an antiandrogen is suggested as first-line therapy for patients with hirsutism or patient-important hirsutism. The lowest effective estrogen dose is advised to minimize the risk of venous thromboembolism (VTE),6 and a highly reliable method of contraception must be used with antiandrogens because of their teratogenic risk.1,5 If hirsutism persists after 6 months of monotherapy, combination therapy with combined OCPs and antiandrogens (such as finasteride or spironolactone, but not flutamide) is recommended because outcomes may be improved. Medical therapy may be combined with direct hair removal methods such as photoepilation, electrolysis, and topical therapies such as eflornithine. Photoepilation is recommended for women with darker hair and electrolysis for women with lighter hair.

Benefits and Harms

By referring to patient-important hirsutism, the guideline acknowledges that hirsutism can significantly affect patient well-being, noting that the risks of OCPs, antiandrogens, and hair removal are relatively low in most women. The principal potential harm with OCPs is VTE, and with antiandrogens it is teratogenicity. Flutamide is not recommended because of hepatotoxicity. Benefits and harms for direct hair removal include the relative efficacy of the treatment, pain, cost, and patient convenience. The new guideline has lowered the threshold for pursuing screening for hyperandrogenic disorders, which may improve detection of these rare but significant conditions but potentially triples the number of women tested, generates false-positive results, and increases costs.

Discussion

The guideline provides recommendations for the diagnosis and treatment of hirsutism in premenopausal women, with detailed information on pharmacologic, cosmetic, and direct hair removal therapies. It includes several useful tables providing recommendations for prescribing antiandrogens and OCPs, with a flow diagram on diagnosis and treatment.1 Menstrual irregularity, infertility, galactorrhea, hypothyroidism, Cushing syndrome, acromegaly, central obesity, acanthosis nigricans, clitoromegaly, or sudden-onset or rapidly progressive hirsutism raise the possibility of a hyperandrogenic endocrine disorder. Although pharmacologic treatment of hirsutism is dependent on the etiology of abnormal hair growth, the majority of women who present in the primary care setting have either polycystic ovary syndrome or idiopathic hirsutism, treated similarly. That said, a correct diagnosis may identify serious conditions such as tumors and have therapeutic implications for other health issues, including fertility and metabolic risk. Despite a thin evidence base, the authors have carefully synthesized current knowledge using commissioned and updated systematic reviews.

Areas in Need of Future Study or Ongoing Research

Uniform laboratory standards for determining free testosterone levels are required. Longer-term data on diagnostic yield, cost, and patient satisfaction in various subgroups would be valuable, particularly given the recommendation to expand screening to include all women with a positive hirsutism score, a somewhat subjective clinical measure.

Box Section Ref ID

Related Guidelines and Other Resources

Ferriman-Gallwey scoring system for hirsutism

Epidemiology, diagnosis and management of hirsutism. Hum Reprod Update. 2012;18(2):146-170.

Bode et al. Am Fam Physician. 2012;85(4):373-380.

van Zuuren EJ, Fedorowicz Z. JAMA. 2015;314(17):1863-1864.

Section Editor: Edward H. Livingston, MD, Deputy Editor, JAMA.
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Article Information

Corresponding Author: Mizuho S. Mimoto, MD, PhD, University of Chicago, 5841 S Maryland Ave, MC 1027, Chicago, IL 60637 (mizuho.mimoto@uchospitals.edu).

Published Online: March 9, 2018. doi:10.1001/jama.2018.2611

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Mimoto reports that her spouse receives salary/stock income from AbbVie. No other disclosures were reported.

References
1.
Martin  KA, Anderson  RR, Chang  RJ,  et al.  Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline  [published online March 7, 2018].  J Clin Endocrinol Metab. https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2018-00241.Google Scholar
2.
Pasch  L, He  SY, Huddleston  H,  et al.  Clinician vs self-ratings of hirsutism in patients with polycystic ovarian syndrome.  JAMA Dermatol. 2016;152(7):783-788.PubMedGoogle ScholarCrossref
3.
Martin  KA, Chang  RJ, Ehrmann  DA,  et al.  Evaluation and treatment of hirsutism in premenopausal women.  J Clin Endocrinol Metab. 2008;93(4):1105-1120.PubMedGoogle ScholarCrossref
4.
Rosner  W, Auchus  RJ, Azziz  R,  et al.  Utility, limitations, and pitfalls in measuring testosterone.  J Clin Endocrinol Metab. 2007;92(2):405-413.PubMedGoogle ScholarCrossref
5.
Sam  S, Ehrmann  DA.  Hormonal evaluation of hyperandrogenism in women.  JAMA. 2015;314(23):2557-2558.PubMedGoogle ScholarCrossref
6.
Stegeman  BH, de Bastos  M, Rosendaal  FR,  et al.  Different combined oral contraceptives and the risk of venous thrombosis.  BMJ. 2013;347:f5298.PubMedGoogle ScholarCrossref
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