Workup and Management of Hirsutism in Adult Women
Initial Clinical Assessment
Begin by quantifying hirsutism severity and identifying red-flag features that suggest serious underlying pathology, particularly androgen-secreting tumors or Cushing's syndrome. 1
Key History and Physical Examination Elements
- Menstrual pattern: Cycles <23 days (polymenorrhea), >35 days (oligomenorrhea), or absent for >6 months (amenorrhea) indicate endocrine dysfunction 1
- Distribution and severity of hair growth: Terminal hair in androgen-dependent areas (face, chest, abdomen, back) 1
- Onset and progression: Rapid onset over weeks to months is concerning for tumor 1
- Associated signs of hyperandrogenism: Severe acne, androgenetic alopecia, clitoromegaly 1
- Metabolic indicators: Waist-hip ratio >0.9 (truncal obesity), acanthosis nigricans (dark velvety skin in neck/axillae indicating insulin resistance) 1
- Cushing's features: Buffalo hump, moon facies, wide violaceous striae—these require immediate endocrinology referral 1
- Pelvic examination: Assess for adnexal masses suggesting ovarian tumors 1
Laboratory Workup
When to Test
Mild hirsutism without other hyperandrogenic signs (normal menses, no acne, no virilization) does NOT require routine endocrine testing. 1 However, full endocrine evaluation is mandatory when hirsutism occurs with oligomenorrhea, amenorrhea, infertility, clitoromegaly, truncal obesity, or rapid progression. 1
Essential Laboratory Panel
- Total testosterone or free/bioavailable testosterone: Levels >200 ng/dL strongly suggest androgen-secreting tumor and require imaging 1
- DHEAS (dehydroepiandrosterone sulfate): Elevated in adrenal sources 1
- Androstenedione 1
- 17-hydroxyprogesterone: Consider for non-classical congenital adrenal hyperplasia (21-hydroxylase deficiency) based on clinical suspicion 1
- LH, FSH: Elevated LH:FSH ratio supports PCOS 1
- Prolactin: Exclude hyperprolactinemia 1
- TSH: Exclude thyroid dysfunction 1
- Fasting glucose and insulin: Assess for insulin resistance 1
Imaging
- Pelvic ultrasound: Identify polycystic ovaries (>10 peripheral cysts, 2-8 mm diameter, thickened ovarian stroma) in suspected PCOS 1
- Adrenal/ovarian imaging (CT or MRI): Required when testosterone >200 ng/dL to locate tumor 1
Diagnosis of Common Causes
Polycystic Ovary Syndrome (PCOS)
PCOS accounts for 70-80% of hirsutism cases and is diagnosed using the Rotterdam criteria: any 2 of 3 features—hyperandrogenism (clinical or biochemical), ovulatory dysfunction, or polycystic ovaries on ultrasound. 1 In adolescents, diagnosis requires both hyperandrogenism AND persistent oligomenorrhea. 1
Idiopathic Hirsutism
Diagnosis of exclusion: hirsutism with normal ovulatory function and normal androgen levels, accounting for 5-15% of cases. 2
Other Causes
- Non-classical congenital adrenal hyperplasia: Elevated 17-hydroxyprogesterone 1
- Androgen-secreting tumors: Total testosterone >200 ng/dL 1
- Cushing's syndrome: Clinical features plus confirmatory testing 1
- Medications: Exogenous androgens, certain antiepileptics 1
Treatment Algorithm
Step 1: First-Line Therapy for PCOS-Related Hirsutism
Initiate combined oral contraceptives (COCs) containing non-androgenic progestins (avoid norethisterone derivatives and levonorgestrel) PLUS topical retinoid and benzoyl peroxide from day 1. 1
COC Mechanism and Selection
- COCs suppress ovarian androgen production, increase sex hormone-binding globulin, reduce 5-alpha-reductase activity, and block androgen receptors 1
- Drospirenone-containing COCs are preferred for their anti-androgenic properties 1
- Absolute contraindications: Smoking ≥15 cigarettes/day at age ≥35, uncontrolled hypertension (≥160/100 mmHg), history of venous thromboembolism or ischemic heart disease, active liver disease, breast cancer 1
- Pre-treatment assessment requires medical history and blood pressure measurement; routine Pap smear and pelvic exam are no longer mandatory 1
Topical Therapy (Simultaneous Initiation)
- Topical retinoids (adapalene, tretinoin): First-line for comedonal acne and maintenance 1
- Benzoyl peroxide: Prevents bacterial resistance, use with any antibiotic therapy 1
- Azelaic acid 15-20%: Adjunct for post-inflammatory hyperpigmentation 1
- Topical eflornithine hydrochloride 13.9% cream: FDA-approved for unwanted facial hair; 32% of patients show marked improvement after 24 weeks versus 8% with vehicle 3
Step 2: Add Spironolactone if Inadequate Response at 3-6 Months
If acne or hirsutism persists after 3-6 months of COCs, add spironolactone 50-100 mg daily (up to 200 mg daily studied safely). 1 Spironolactone achieves clear skin or marked improvement in 66-85% of women. 1 It reduces testosterone synthesis, blocks androgen receptors, inhibits 5-alpha-reductase, and increases SHBG. 1 Combination with drospirenone-containing COCs is safe and does not increase clinically significant hyperkalemia risk. 1
Step 3: Add Metformin for Metabolic Features
In patients with insulin resistance (obesity, acanthosis nigricans, documented metabolic abnormalities), add metformin 500 mg 2-3 times daily. 1 Approximately 72% show significant improvement after 24 weeks, with normalization of ovarian and adrenal androgen excess. 1 Best responders are those with menstrual-related flares or classic PCOS phenotypes. 1
Step 4: Consider Isotretinoin for Severe/Refractory Cases
Reserve isotretinoin (0.5-1 mg/kg/day) for severe nodulocystic acne failing optimized hormonal therapy. 1 Retrospective data show ~41% improvement, with better outcomes in milder disease. 4 Isotretinoin can be safely combined with COCs and spironolactone but requires strict pregnancy-prevention programs (iPLEDGE). 1
Alternative Anti-Androgens
- Finasteride (1.25-5 mg/day): Beneficial in small case series, particularly in adolescents with endocrine comorbidities 1
- Cyproterone acetate: Effective in combination with ethinyl estradiol; 55% of women improved in retrospective series 4
- Flutamide: Effective but hepatotoxicity concerns limit use 5
Special Considerations
Weight Loss and Lifestyle Modification
A 5% weight reduction improves metabolic and reproductive abnormalities in obese women with PCOS-related hirsutism. 1
Cosmetic and Mechanical Treatments
- Topical eflornithine: Apply twice daily; marked improvement seen at 8 weeks, continuing through 24 weeks; hair growth returns to pretreatment levels within 8 weeks of discontinuation 3
- Hair removal techniques: Shaving, waxing, plucking, electrolysis, laser therapy 1
Reproductive Concerns
For women desiring pregnancy or with infertility, refer to gynecology; clomiphene citrate is preferred over COCs in this setting. 1
Monitoring and Expected Outcomes
- Acne improvement: Expected by month 3, maximal by month 6 of COC therapy 1
- Hirsutism reduction: Requires 6-12 months of combined hormonal therapy (COC ± spironolactone) 1
- Metabolic parameters: Reassess at 3-6 months 1
- Blood pressure: Monitor before COC initiation and periodically 1
- Potassium monitoring: Advised only when spironolactone is used long-term with other potassium-sparing agents 1
Common Pitfalls
- Expecting rapid results: Counsel patients that visible improvement takes 3-6 months for acne and 6-12 months for hirsutism; lifelong therapy may be needed to prevent recurrence 1, 6
- Using androgenic progestins: Avoid norethisterone derivatives and levonorgestrel, which worsen hirsutism 1
- Missing tumor diagnosis: Always investigate testosterone >200 ng/dL with imaging 1
- Overlooking Cushing's syndrome: Buffalo hump, moon facies, and wide violaceous striae mandate endocrinology referral 1
- Inadequate contraception with anti-androgens: Ensure adequate contraception when using spironolactone, finasteride, or other anti-androgens due to teratogenicity risk 5