What oral anti‑androgen is recommended as first‑line therapy for a woman of childbearing age with moderate‑to‑severe acne, hirsutism, or female pattern hair loss, including appropriate dosing, monitoring, contraindications, and alternative options?

Anti-Androgen Therapy in Dermatology

First-Line Recommendation

Spironolactone 50-100 mg daily is the recommended first-line oral anti-androgen for women of childbearing age with moderate-to-severe acne, hirsutism, or female pattern hair loss, always combined with reliable contraception. 1, 2

Treatment Algorithm by Indication

For Acne in Women of Childbearing Age

• Start with spironolactone 50-100 mg daily combined with topical retinoid (adapalene 0.1-0.3%) plus benzoyl peroxide 2.5-5% as the foundation of therapy for moderate-to-severe inflammatory acne with hormonal patterns (premenstrual flares, jawline distribution). 1, 3

• Spironolactone may be used alone or in combination with oral antibiotics (doxycycline 100 mg daily), but always with concurrent benzoyl peroxide to prevent resistance. 1, 3

• Combined oral contraceptives (COCs) containing ethinyl estradiol with norgestimate, norethindrone, or drospirenone are FDA-approved alternatives that reduce inflammatory lesions by 62% at 6 months and can be used as monotherapy or combined with topical agents. 1, 3, 4

• COCs should be avoided within 2 years of menarche or in patients <14 years of age unless clinically warranted, due to concerns about bone mass development. 1

For Hirsutism in Women of Childbearing Age

• Cyproterone acetate (CPA) 50 mg/day for 20 days out of 28, combined with estrogen, is first-line treatment for moderate-to-severe hirsutism in regions where available. 5, 6

• Spironolactone 100-200 mg daily with concurrent COC is recommended as second-line therapy when CPA causes side effects or is contraindicated, or as first-line in countries where CPA is unavailable. 5, 2, 6

• Flutamide 250-500 mg/day or finasteride 5 mg/day are reserved as third-line therapy for severe hirsutism with contraindications to first-line agents, though neither has market authorization for this indication. 5, 6

For Female Pattern Hair Loss

• Spironolactone 100-200 mg daily is the primary medical treatment, with overall improvement rates of 56.6% and higher efficacy (65.8%) when combined with topical minoxidil versus monotherapy (43.2%). 2, 7

• Continuous treatment is required to sustain effect, though long-lasting benefits may persist 33.7 months after discontinuation in some patients. 2, 8

Dosing and Titration Strategy

• Start spironolactone at 25-50 mg daily and titrate to 100-200 mg daily based on response and tolerability. 1, 3, 2

• For acne: 50-100 mg daily is typically sufficient. 1, 3

• For hirsutism and hair loss: 100-200 mg daily provides optimal efficacy, though higher doses increase adverse effects. 2, 6, 7

• Dosing can be once daily or divided twice daily to minimize side effects. 2

Mandatory Contraception Requirements

• Spironolactone is absolutely contraindicated in pregnancy due to teratogenic effects (feminization of male fetuses) and must be combined with reliable contraception in all women of childbearing potential. 2, 6

• COCs serve dual purposes: providing contraception and enhancing anti-androgen efficacy by suppressing ovarian androgen production. 1, 5, 6

• The combination of drospirenone-containing COC (3 mg drospirenone/30 µg ethinyl estradiol) with spironolactone 100 mg daily does not cause clinically significant hyperkalemia. 1

Monitoring Requirements

• No routine potassium monitoring is needed in healthy patients without risk factors for hyperkalemia (renal disease, concurrent ACE inhibitors/ARBs, potassium supplements). 3, 4

• Baseline blood pressure measurement is recommended before initiating therapy. 1

• Monitor for menstrual irregularities, particularly intermenstrual bleeding, which occurs in 68.2% of patients, especially those with classic PCOS phenotype. 8

Expected Timeline for Response

• Acne improvement becomes apparent after 3 months, with maximal benefit at 6 months. 1, 3

• Hirsutism shows improvement within 6-12 months of treatment. 6

• Hair loss requires 6-12 months to assess response, with some patients showing continued improvement beyond 12 months. 7

Common Adverse Effects and Management

• Menstrual irregularities (intermenstrual bleeding, irregular cycles) are the most common side effect, occurring in up to 68% of patients; concurrent COC use prevents this. 1, 8, 6

• Breast tenderness, fatigue, and dizziness occur but are generally mild and dose-dependent. 2, 6

• Scalp pruritus or increased dandruff occurs in 18.9% of patients with hair loss. 7

• Hyperkalemia risk is minimal in healthy patients but requires monitoring in those with renal impairment or concurrent medications affecting potassium. 1, 3

Alternative Anti-Androgen Options

Combined Oral Contraceptives (COCs)

• FDA-approved COCs for acne include formulations with norgestimate, norethindrone/ferrous fumarate, or drospirenone/levomefolate for females ≥14-15 years. 1

• COCs reduce inflammatory acne lesions by 62% at 6 months and provide additional benefits including menstrual regulation and reduced menorrhagia. 1, 3, 4

• Drospirenone-containing COCs have anti-androgenic properties due to drospirenone being a spironolactone analog. 1

Finasteride

• Finasteride 5 mg daily is the least effective anti-androgen but has minimal adverse effects and can be used in select cases, particularly in male patients with hidradenitis suppurativa. 1, 5, 6

• It is reserved as third-line therapy for severe hirsutism when other options fail or are contraindicated. 5, 6

Flutamide

• Flutamide 250-500 mg/day is highly effective for hirsutism within 6-12 months but carries risk of fatal hepatotoxicity requiring careful liver function monitoring. 1, 5, 6

• Use is discouraged except where benefit warrants the risk, as third-line therapy only. 1, 5

Metformin

• Metformin is suggested for adolescent patients with hidradenitis suppurativa, especially with insulin resistance, though it has weaker anti-androgenic effects than spironolactone. 1

Critical Contraindications

• Pregnancy and breastfeeding (absolute contraindication for spironolactone, finasteride, and flutamide due to teratogenic effects). 2, 6

• Male patients should not receive spironolactone due to feminization risk (gynecomastia, decreased libido, erectile dysfunction). 2

• Significant renal impairment or hyperkalemia. 3, 4

• Concurrent use of potassium-sparing diuretics, ACE inhibitors, or ARBs without careful monitoring. 1

Common Pitfalls to Avoid

• Never prescribe spironolactone without ensuring reliable contraception in women of childbearing potential. 2, 6

• Do not use anti-androgens as monotherapy for acne; always combine with topical retinoid and benzoyl peroxide to address all pathogenic factors. 1, 3, 4

• Avoid unnecessary potassium monitoring in healthy patients, which increases cost and patient anxiety without clinical benefit. 3, 4

• Do not discontinue therapy prematurely; minimum 6-month trial is needed to assess efficacy for hirsutism and hair loss. 2, 6, 7

• Avoid using flutamide without careful consideration of hepatotoxicity risk and mandatory liver function monitoring. 1, 6

Maintenance and Long-Term Management

• Continuous treatment is required to sustain anti-androgen effects, though some patients (particularly those with PCOS) show prolonged benefits 33.7 months after discontinuation. 2, 8

• After achieving acne clearance, transition to topical retinoid monotherapy indefinitely to prevent recurrence. 3, 4

• For hirsutism and hair loss, ongoing anti-androgen therapy is typically needed, as discontinuation leads to relapse in many patients within 17.5 months. 8

• Long-term hair removal treatments (electrolysis or laser) should be offered as adjunctive therapy for hirsutism. 5