Is Spironolactone an Anti-Androgen?
Yes, spironolactone is definitively an anti-androgen that blocks testosterone and dihydrotestosterone from binding to androgen receptors in target tissues, while also decreasing testosterone production. 1
Mechanism of Anti-Androgenic Action
Spironolactone functions as an anti-androgen through multiple complementary pathways:
Direct receptor blockade: Competitively inhibits testosterone and dihydrotestosterone (DHT) binding to androgen receptors in skin, hair follicles, and sebaceous glands 1
Decreased androgen production: Reduces testosterone synthesis in the ovaries and adrenal glands 1, 2
Enhanced androgen metabolism: May inhibit 5α-reductase enzyme (which converts testosterone to the more potent DHT) and increases steroid hormone-binding globulin, reducing free testosterone availability 1
Cellular-level effects: Directly inhibits proliferation of androgen-sensitive cells (such as sebocytes) in a dose-dependent manner, demonstrating antagonistic effects against both testosterone and DHT at the cellular level 3
Clinical Evidence of Anti-Androgenic Effects
The anti-androgenic properties of spironolactone are demonstrated across multiple androgen-dependent conditions:
For acne treatment: 77.4% of patients showed improvement compared to 22% with placebo (RR 3.60), with the drug working by blocking androgen receptors on sebocytes and reducing sebum production 1
For hirsutism: Approximately 77% of patients experience subjective improvement in hair growth compared to 22% with placebo, with good to very good clinical results in 80% of patients treated long-term 4, 5
For androgenetic alopecia: 84-86% of women show improvement with 40-66% achieving complete clearance by blocking androgen receptors on hair follicles 6
Hormonal Effects Confirming Anti-Androgenic Activity
Measurable hormonal changes demonstrate spironolactone's anti-androgenic mechanism:
- Serum total testosterone decreases significantly with both 100 mg and 200 mg daily doses 2
- Peripherally derived DHT decreases significantly with treatment 2
- Androstenedione (an androgen precursor) decreases with 200 mg daily 2
- These effects occur within 4 weeks of treatment initiation 7
Important Clinical Caveats
Pregnancy contraindication: The FDA explicitly warns that spironolactone may affect sex differentiation of male fetuses due to its anti-androgenic properties, with animal studies showing feminization of male fetuses at doses of 50-200 mg/kg/day 8
Gender-specific use: Spironolactone is not used in men with androgenetic alopecia specifically because of the risk of feminization (including gynecomastia), which occurred in all 23 men in one Japanese study, leading to premature discontinuation 1, 6
Primary mechanism: While spironolactone is classified as an aldosterone receptor antagonist (its FDA-approved indication), its anti-androgenic effects are well-established and clinically significant, making it effective for androgen-dependent dermatologic conditions despite not being FDA-approved for these uses 1