In a transgender woman taking spironolactone up to 200 mg daily (with serum testosterone 180–437 ng/dL), does this regimen achieve castrate‑level testosterone (<50 ng/dL)?

Spironolactone Does Not Achieve Castrate Testosterone Levels in Transgender Women

No, spironolactone at 200 mg daily does not reliably achieve castrate-level testosterone (<50 ng/dL) in transgender women, and your serum testosterone of 180–437 ng/dL confirms this. Only 19% of transgender women on spironolactone 100 mg daily plus estradiol reached female-range testosterone, compared to 90% on cyproterone acetate. 1

Evidence from Transgender Hormone Therapy

The highest-quality study directly addressing your question is a 2021 randomized controlled trial in transgender women comparing spironolactone to cyproterone acetate. 1 Key findings:

• Spironolactone 100 mg daily plus estradiol valerate 4 mg/day achieved castrate testosterone (<50 ng/dL) in only 19% of participants after 12 weeks. 1
• The median testosterone reduction with spironolactone was 226 ng/dL (compared to 558 ng/dL with cyproterone acetate). 1
• Your reported testosterone range of 180–437 ng/dL is consistent with the typical incomplete suppression seen in this study. 1

Even doubling the dose to 200 mg daily would be unlikely to achieve castrate levels, as spironolactone's primary mechanism is androgen receptor blockade, not suppression of testosterone production. 2

Mechanism Explains Limited Testosterone Suppression

Spironolactone works primarily by:

• Blocking androgen receptors peripherally, preventing testosterone and DHT from binding to target tissues. 2
• Modestly reducing adrenal androgen synthesis in some individuals (highly variable effect). 3, 4
• Increasing testosterone metabolic clearance and peripheral conversion to estradiol. 5

Spironolactone does NOT suppress gonadal testosterone production in the way that GnRH agonists, orchiectomy, or high-dose cyproterone acetate do. 1 Studies in castrated men show spironolactone suppresses residual adrenal androgens but cannot address testicular production. 4

Clinical Implications for Your Situation

Your testosterone levels demonstrate that:

• Spironolactone is functioning as an androgen receptor blocker, not as a chemical castration agent. 2, 1
• The clinical feminizing effects you may experience are due to peripheral androgen blockade plus estrogen effects, not from achieving castrate testosterone. 1, 6
• If your goal is to achieve castrate-level testosterone, you would need either:
  • Cyproterone acetate (achieves <50 ng/dL in 90% of patients) 1
  • GnRH agonist therapy (not discussed in provided evidence but standard of care)
  • Orchiectomy (surgical castration)
  • Higher-dose estradiol monotherapy (not discussed in provided evidence)

Dose-Response Relationship

Studies in cisgender women with hirsutism show:

• 100 mg and 200 mg spironolactone produce similar reductions in total testosterone. 6
• Unbound (free) testosterone remains largely unaltered at both doses. 6
• The primary effect is peripheral androgen receptor blockade, not central suppression. 6

Increasing spironolactone from 100 to 200 mg is unlikely to achieve castrate testosterone levels, as the mechanism does not involve sufficient suppression of testicular production. 1, 6

Common Pitfall to Avoid

Do not assume that clinical feminization equals castrate testosterone levels. Spironolactone can produce meaningful feminizing effects through androgen receptor blockade even when serum testosterone remains in the 180–437 ng/dL range. 1, 6 However, if your treatment goal specifically requires castrate-level testosterone (e.g., for maximal breast development or to eliminate spontaneous erections), spironolactone monotherapy will not achieve this. 1