Does Spironolactone Decrease Testosterone in Women?
Spironolactone does not consistently decrease total serum testosterone levels in women, but it effectively blocks testosterone activity at the androgen receptor level in target tissues like skin, which is why it successfully treats hyperandrogenic conditions like hirsutism, acne, and androgenic alopecia. 1, 2
Mechanism of Androgen Suppression
Spironolactone works through direct androgen receptor blockade rather than primarily lowering circulating testosterone levels:
The drug competitively inhibits testosterone and dihydrotestosterone from binding to androgen receptors on sebocytes and hair follicles, directly reducing sebum production and androgen-mediated hair growth. 1, 2
Spironolactone may also decrease synthesis of androgen precursors in the adrenal glands and inhibit 5α-reductase enzyme activity, contributing to its antiandrogen effects. 1, 3
The American Academy of Dermatology emphasizes that spironolactone's therapeutic benefit comes from peripheral antiandrogen activity at the tissue level, not from systemic testosterone suppression. 4
Evidence on Testosterone Levels
The relationship between spironolactone and serum testosterone is complex and often counterintuitive:
Total serum testosterone levels typically show no significant change during spironolactone therapy in most studies. 5, 6
One study found that spironolactone may actually cause a redistribution of testosterone fractions, with a decrease in SHBG-bound testosterone but an increase in albumin-bound and free testosterone (the bioavailable fractions). 5
Despite this paradoxical increase in free testosterone levels, clinical improvement in hirsutism and other hyperandrogenic symptoms still occurs because spironolactone blocks testosterone from binding to its receptors. 5
Some studies report that spironolactone can lower plasma testosterone by altering its formation and metabolism and by increasing peripheral conversion of testosterone to estradiol, though this effect is inconsistent. 6
Clinical Effectiveness Despite Minimal Testosterone Reduction
The disconnect between testosterone levels and clinical response is important to understand:
Large observational studies demonstrate that 84-86% of women show improvement with spironolactone, with 40-66% achieving complete clearance of acne, despite minimal changes in serum testosterone. 1
In hirsutism studies, patients achieved a 54% reduction in hirsutism scores after one year of spironolactone 50 mg twice daily, underscoring the peripheral antiandrogen activity independent of systemic testosterone suppression. 4
A study of 63 women with PCOS-related hyperandrogenic skin disorders showed significant improvement in all patients after a mean treatment duration of 25.7 months, with prolonged effects lasting 33.7 months after discontinuation in many patients. 7
Practical Dosing for Antiandrogen Effect
Start with 100 mg daily in the evening as the typical initial dose for hyperandrogenic skin conditions. 1, 3
The usual maximum dose is 200 mg daily, though doses above 100 mg increase side effects disproportionately to therapeutic benefit. 1, 3
Expect 3 months for initial response and 5-6 months for maximum response, as the drug requires several months to reach full effectiveness. 1
If inadequate response after 3 months, increase in 25-50 mg increments every 3 months, with a maximum of 200 mg daily. 1
Critical Contraindication: Testosterone Therapy
Spironolactone is absolutely contraindicated in women receiving testosterone therapy because it directly opposes and cancels out the therapeutic effects of testosterone. 3, 2
The American Academy of Dermatology explicitly recommends against using spironolactone for acne or other conditions in women on testosterone therapy, as it counteracts the desired effects of treatment. 2
Common Pitfall to Avoid
Do not use serum testosterone levels to monitor spironolactone efficacy. 5 The drug works through receptor blockade, not testosterone suppression, so testosterone levels may remain unchanged or even show paradoxical increases in free fractions while clinical symptoms improve. Clinical assessment of hirsutism, acne, or hair loss is the appropriate monitoring parameter, not hormone levels. 4, 5