What is the appropriate evaluation and management for a woman with excessive androgen‑dependent hair growth (hirsutism) who is not planning pregnancy?

Evaluation and Management of Hirsutism in Women Not Planning Pregnancy

For a woman with hirsutism who is not planning pregnancy, initiate combined oral contraceptives (COCs) containing a non-androgenic progestin as first-line therapy, combined with topical eflornithine and mechanical hair removal methods, while simultaneously conducting targeted endocrine evaluation based on clinical severity and associated features. 1

Initial Clinical Assessment

Confirm true hirsutism by documenting terminal (coarse) hair growth in androgen-dependent areas using the modified Ferriman-Gallwey (mFG) scoring system, with a score ≥8 indicating abnormal hirsutism requiring endocrine evaluation. 2

Key clinical features to assess include:

• Menstrual pattern: Cycles <23 days (polymenorrhea), >35 days (oligomenorrhea), or absent for >6 months (amenorrhea) suggest underlying endocrine dysfunction, most commonly PCOS. 1
• Associated hyperandrogenic signs: Severe or persistent acne, androgenetic alopecia (male-pattern hair loss), clitoromegaly, and truncal obesity warrant comprehensive hormonal testing. 1, 3
• Metabolic indicators: Waist-hip ratio >0.9 and acanthosis nigricans (dark, velvety skin in neck/axillae) indicate insulin resistance. 1
• Red-flag features: Buffalo hump, moon facies, and wide violaceous striae suggest Cushing's syndrome and require immediate endocrinology referral. 1

Laboratory Evaluation Strategy

First-Line Testing (for mFG ≥8 or moderate-to-severe hirsutism)

Obtain morning (8-10 AM) fasting blood draw to maximize diagnostic accuracy and allow concurrent metabolic screening: 3

• Total testosterone (TT) measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) – sensitivity 74%, specificity 86%. 3
• Free testosterone (FT) calculated via free androgen index (FAI = TT/SHBG ratio) or measured by equilibrium dialysis – sensitivity 89%, specificity 83%. 3
• Sex hormone-binding globulin (SHBG) for FAI calculation when LC-MS/MS unavailable. 3

Critical threshold: Total testosterone >200 ng/dL is highly suggestive of androgen-secreting tumor and requires urgent imaging. 4, 2

Comprehensive Metabolic Panel (all PCOS-suspected patients)

• Fasting glucose followed by 2-hour 75-gram oral glucose tolerance test to screen for diabetes and insulin resistance. 3
• Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) to assess cardiovascular risk. 3
• Thyroid-stimulating hormone (TSH) to exclude thyroid disease. 3
• Prolactin to rule out hyperprolactinemia. 3

Second-Line Testing (when TT/FT normal but clinical suspicion high)

• Androstenedione (A4) – sensitivity 75%, specificity 71%. 3
• DHEAS – sensitivity 75%, specificity 67%; levels >600 μg/dL suggest adrenal source and raise concern for adrenocortical carcinoma. 3
• 17-hydroxyprogesterone (early morning) if nonclassical congenital adrenal hyperplasia suspected. 1

Important caveat: Avoid direct immunoassay methods for free testosterone in women due to poor accuracy at low concentrations. 3

Diagnostic Algorithm by Cause

PCOS (accounts for 70-80% of hirsutism cases) requires 2 of 3 Rotterdam criteria: 1, 5

• Clinical or biochemical hyperandrogenism
• Ovulatory dysfunction (oligomenorrhea/anovulation)
• Polycystic ovarian morphology on ultrasound (>10 peripheral cysts, 2-8 mm diameter)

In adolescents, PCOS diagnosis requires both hyperandrogenism AND persistent oligomenorrhea. 5

Idiopathic hirsutism (10-15% of cases) is diagnosed by exclusion when hirsutism occurs with normal ovulatory function and normal androgen levels. 6, 7

Rare but serious causes to exclude:

• Androgen-secreting tumors (testosterone >200 ng/dL, rapid virilization)
• Cushing's syndrome (buffalo hump, moon facies, purple striae)
• Nonclassical congenital adrenal hyperplasia (elevated 17-hydroxyprogesterone)
• Hyperprolactinemia, thyroid disease 1, 5

Treatment Algorithm

Step 1: First-Line Hormonal Therapy

Initiate combined oral contraceptives (COCs) containing non-androgenic progestins (drospirenone, norgestimate, desogestrel): 1

• Mechanism: Suppress ovarian androgen production, increase SHBG, reduce 5α-reductase activity, block androgen receptors. 1
• Contraindications to verify: Smoking ≥15 cigarettes/day at age ≥35, uncontrolled hypertension (≥160/100 mmHg), history of venous thromboembolism or ischemic heart disease. 1
• Avoid: Norethisterone derivatives and levonorgestrel-containing COCs, which have androgenic activity and worsen hirsutism. 1
• Expected timeline: Hirsutism reduction requires 6-12 months of continuous therapy. 1

Step 2: Add Anti-Androgen if Inadequate Response at 6 Months

Spironolactone 50-100 mg daily (can increase to 200 mg if needed): 1

• Efficacy: 66-85% achieve clear skin or marked improvement. 1
• Mechanism: Reduces testosterone synthesis, competitively blocks androgen receptors, inhibits 5α-reductase, increases SHBG. 1
• Safety: Combination with drospirenone-containing COCs does not increase clinically significant hyperkalemia risk. 1

Alternative anti-androgens (where available):

• Cyproterone acetate combined with oral contraceptive (safest and most effective per Dutch guidelines). 8
• Finasteride (5α-reductase inhibitor)
• Flutamide (monitor liver function) 6

Step 3: Metabolic Management for Insulin Resistance

Metformin 500 mg 2-3 times daily for patients with: 1

• Obesity (BMI >30)
• Acanthosis nigricans
• Documented insulin resistance or prediabetes

Efficacy: 72% show significant improvement after 24 weeks, with normalization of ovarian and adrenal androgen excess. 1

Weight loss: 5% weight reduction improves metabolic and reproductive abnormalities in obese PCOS patients. 1

Step 4: Cosmetic and Mechanical Therapies (Initiated Concurrently)

• Topical eflornithine hydrochloride 13.9% cream applied twice daily to face to slow hair growth. 1, 6
• Mechanical removal: Shaving, waxing, plucking (temporary); electrolysis or laser therapy (more permanent). 1
• Laser hair removal: Most effective for dark hair on light skin; requires multiple sessions. 6

Monitoring and Follow-Up

• Re-evaluate at 3-6 months: Assess menstrual regularity (1-3 cycles), metabolic parameters, and early hirsutism response. 1
• Full hirsutism assessment at 6-12 months: Visible reduction in terminal hair growth expected. 1
• Long-term surveillance: Annual metabolic screening (glucose, lipids) for PCOS patients given increased cardiovascular and diabetes risk. 3

Common Pitfalls to Avoid

• Do not delay treatment while awaiting complete hair removal; pharmacologic therapy takes 6-12 months to show effect, so mechanical removal provides immediate cosmetic benefit. 1
• Do not use topical or systemic antibiotics for hirsutism; microbiologic testing is not indicated. 9
• Do not perform routine endocrine testing for mild hirsutism (mFG <8) without other hyperandrogenic signs. 1
• Do not miss androgen-secreting tumors: Any testosterone >200 ng/dL or rapid virilization (weeks to months) requires urgent pelvic ultrasound and adrenal imaging. 4, 2
• Do not attribute all hirsutism to PCOS: 10-15% have idiopathic hirsutism with normal androgens and ovulation. 6, 7

When to Refer

• Endocrinology: Cushing's syndrome features, testosterone >200 ng/dL, DHEAS >600 μg/dL, suspected adrenal hyperplasia, or refractory hirsutism despite 12 months of combination therapy. 1, 5
• Gynecology: Infertility concerns, marked menstrual irregularities, or adnexal masses on examination. 1
• Dermatology: Severe acne requiring isotretinoin, persistent folliculitis, or androgenic alopecia not responding to hormonal therapy. 9, 1