What is the approach to managing hyperandrogenism in women?

Approach to Hyperandrogenism in Women

Begin with first-line laboratory testing using total testosterone (TT) and free testosterone (FT) measured by LC-MS/MS, combined with clinical assessment of hirsutism (using modified Ferriman-Gallwey score), acne, and androgenic alopecia to establish the diagnosis of hyperandrogenism. 1, 2

Initial Diagnostic Evaluation

Clinical Assessment

• Hirsutism: Score terminal hair growth in male-pattern areas using the modified Ferriman-Gallwey method; a score ≥6 indicates hirsutism in Caucasian populations 3, 4
• Acne: Document persistent or severe acne, particularly if resistant to standard treatments 2
• Androgenic alopecia: Assess for male-pattern hair loss 2
• Virilization signs: Check for clitoromegaly, voice deepening, increased muscle mass—these suggest more severe androgen excess or possible tumor 2, 5
• Menstrual patterns: Document oligomenorrhea or amenorrhea 2
• Metabolic signs: Look for acanthosis nigricans (insulin resistance marker), truncal obesity, elevated BMI 2

First-Line Laboratory Tests

Use LC-MS/MS methodology when available for highest accuracy 1, 2:

• Total testosterone (TT) 1, 2
• Free testosterone (FT): Measured by equilibrium dialysis or ammonium sulfate precipitation, or calculated using free androgen index (FAI) if mass spectrometry unavailable 1, 2
• Important caveat: Avoid direct immunoassay methods for FT due to poor accuracy at low serum concentrations 1

Second-Line Laboratory Tests (if TT/FT not elevated)

• Androstenedione (A4) 1
• DHEAS (dehydroepiandrosterone sulfate) 1, 2
• Note: These have poorer specificity than testosterone measurements 1
• LH/FSH ratio: A ratio >2 suggests PCOS 2, 6

Exclusion of Secondary Causes

Screen for these conditions before diagnosing PCOS 2, 7:

• TSH: Rule out thyroid disease 2
• Prolactin: Exclude hyperprolactinemia 2
• 17-hydroxyprogesterone: Screen for nonclassic congenital adrenal hyperplasia 2, 3
• 24-hour urinary free cortisol or late-night salivary cortisol: Consider if Cushing's syndrome suspected 2

Red Flags for Androgen-Secreting Tumors

Urgent imaging required if 2, 3:

• Very high testosterone levels (typically >150-200 ng/dL)
• Rapid onset of symptoms
• Progressive virilization
• Age of onset atypical for PCOS

Metabolic Screening

All women with confirmed hyperandrogenism require metabolic assessment 2:

• Fasting glucose and 2-hour oral glucose tolerance test: Screen for diabetes and insulin resistance 2
• Fasting lipid panel: Assess cardiovascular risk 2

Treatment Algorithm

First-Line Pharmacologic Treatment

Combined oral contraceptives (COCs) are the first-line treatment for hyperandrogenism 2, 6:

• Effectively regulate menstrual cycles 2, 6
• Reduce hyperandrogenism 2, 6
• Improve acne and hirsutism 2, 6
• Prevent endometrial hyperplasia in anovulatory women 8

Second-Line: Antiandrogen Therapy

Add antiandrogens for severe hirsutism or inadequate response to COCs 3, 4:

• Cyproterone acetate: Most effective antiandrogen; decreases hair density, regrowth speed, and pigmentation 3
• Spironolactone: Androgen receptor blocker 5, 4
• Flutamide: Alternative androgen receptor blocker 5
• 5α-reductase inhibitors: Can be combined with above 4
• Critical point: Must combine with contraception due to teratogenic risk 3

Adjunctive Treatments

• Topical eflornithine hydrochloride: For facial hirsutism 4
• Cosmetic treatments: Laser therapy, electrolysis, intense pulsed light for long-term hair removal 4
• Metformin: Consider for insulin resistance, particularly in PCOS 7

Lifestyle Modifications

Weight loss should be vigorously encouraged in overweight/obese patients 2, 8:

• Improves metabolic complications 2
• Ameliorates insulin resistance 8
• May improve ovulatory function 8

Timeline for Treatment Response

Set realistic expectations with patients 4:

• Acne: Responds relatively rapidly (weeks to months) 4
• Hirsutism: Improvements observed at 3 months minimum, typically 6-8 months 4
• Androgenic alopecia: Slowest response; may require 12-18 months, and response is variable 4

Common Pitfalls to Avoid

• Do not use direct immunoassays for free testosterone—they are highly inaccurate 1
• Do not diagnose PCOS without excluding secondary causes (thyroid disease, hyperprolactinemia, Cushing's, CAH) 2, 7
• Do not overlook psychological impact of visible symptoms like hirsutism and acne—address as part of comprehensive care 2, 6
• Do not miss androgen-secreting tumors—maintain high suspicion with very elevated androgens or rapid symptom onset 2, 3
• Remember SHBG fluctuations affect TT and FAI results (influenced by age, weight, medications like oral contraceptives) 1