As a transgender woman taking oral estradiol 3 mg daily and spironolactone up to 200 mg daily, with serum testosterone between 180 and 437 ng/dL for several months and loss of nocturnal erections, why wouldn't this regimen and timeline cause permanent penile shrinkage?

Why Your Regimen May Not Cause Permanent Penile Shrinkage

Your testosterone levels remain in the low-normal male range (180-437 ng/dL), which is insufficient to induce the profound hypogonadism required for permanent structural changes to penile tissue. While you've lost nocturnal erections—a sign of reduced androgen activity—your testosterone has not been suppressed to the female reference range (<50 ng/dL), which is the therapeutic target for transgender women. 1, 2

Understanding Testosterone Suppression in Feminizing Therapy

Your Current Hormone Levels Are Inadequate

• Target testosterone for transgender women is <50 ng/dL, not 180-437 ng/dL. 1, 2
• Your regimen (oral estradiol 3 mg daily + spironolactone up to 200 mg daily) is producing suboptimal testosterone suppression—you're achieving only partial androgen blockade, not the complete suppression needed for feminization. 3, 4
• Research shows that nearly one-third of transgender women fail to achieve adequate testosterone suppression even on 6-8 mg daily of oral estradiol, and your 3 mg dose is well below this threshold. 3

Spironolactone's Limited Effectiveness

• Spironolactone does not reliably suppress testosterone production—it primarily blocks androgen receptors peripherally without lowering serum testosterone concentrations. 2, 3
• A 2018 study found that spironolactone did not enhance testosterone suppression and actually impaired achievement of target estradiol levels in transgender women. 3
• A 2021 randomized trial demonstrated that only 19% of transgender women on spironolactone achieved female-range testosterone (<50 ng/dL), compared to 90% on cyproterone acetate. 5

Why Permanent Shrinkage Requires Profound, Sustained Hypogonadism

Mechanism of Penile Atrophy

• Permanent structural changes to penile tissue require prolonged exposure to female-range testosterone levels (<50 ng/dL), not the low-normal male range you're currently experiencing. 1, 2
• Loss of nocturnal erections indicates reduced smooth muscle oxygenation, but reversible functional changes precede irreversible structural atrophy—you're likely experiencing the former, not the latter. 6
• Penile tissue maintains viability through periodic erections and adequate androgen exposure; your testosterone levels (180-437 ng/dL) remain sufficient to prevent permanent collagen deposition and fibrosis. 6

Timeline Considerations

• You mention "several months" of therapy, but permanent structural changes typically require years of profound testosterone suppression to female levels, not months of partial suppression to low-normal male levels. 1, 2
• The loss of nocturnal erections you're experiencing is likely a reversible functional change, not permanent structural atrophy, given your inadequate testosterone suppression. 6

What You Need to Achieve Your Goals

Optimize Your Feminizing Regimen

• Increase oral estradiol to at least 4-6 mg daily to improve testosterone suppression—over 70% of transgender women achieve treatment goals on 4 mg or more. 3
• Consider switching from oral to transdermal estradiol, which achieves more rapid and complete testosterone suppression with lower overall doses. 4
• A 2024 randomized trial found that transdermal estradiol (1-2 patches of 0.1 mg/24 hours) suppressed testosterone to female levels within 2 months in most transgender women. 4

Consider Alternative Anti-Androgens

• Cyproterone acetate 12.5-25 mg daily is far more effective than spironolactone for testosterone suppression, achieving female-range levels in 90% of users versus 19% with spironolactone. 5
• GnRH agonists directly suppress testosterone production at the hypothalamic-pituitary level, providing complete androgen blockade that spironolactone cannot achieve. 2

Monitor Your Hormone Levels

• Check testosterone and estradiol levels every 3-6 months to ensure you're achieving target ranges (testosterone <50 ng/dL, estradiol in cisgender female range). 1, 2
• Your current testosterone levels (180-437 ng/dL) confirm inadequate suppression—this must be corrected to achieve feminization goals. 1, 2

Critical Pitfalls to Avoid

• Do not assume that loss of nocturnal erections equals permanent shrinkage—functional changes precede structural changes, and your testosterone levels suggest you're experiencing the former. 6
• Do not continue your current regimen expecting permanent changes—your testosterone suppression is inadequate, and you're unlikely to achieve feminization goals without optimization. 3, 5
• Do not rely on spironolactone alone for testosterone suppression—it functions primarily as a peripheral androgen receptor blocker, not a testosterone-lowering agent. 2, 3, 5