In a trans woman taking oral estradiol 3 mg daily and spironolactone up to 200 mg daily for several months with serum testosterone 180–437 ng/dL and loss of nocturnal erections, is permanent penile shortening likely?

Risk of Permanent Penile Shortening with Current Hormone Regimen

Your current regimen (oral estradiol 3 mg daily and spironolactone up to 200 mg daily) with testosterone levels remaining in the 180-437 ng/dL range is NOT adequately suppressing testosterone and therefore carries minimal risk of permanent penile shortening at this time, though the loss of nocturnal erections may lead to some reversible tissue changes if prolonged.

Understanding the Mechanism

Permanent penile shortening in transgender women occurs primarily when testosterone is adequately suppressed to female levels (<50 ng/dL) for extended periods, combined with absence of erectile tissue stimulation. 1, 2

• Your testosterone levels (180-437 ng/dL) remain well above the target range of <50 ng/dL that guidelines recommend for feminizing hormone therapy 1, 2
• Normal male testosterone ranges from approximately 300-1000 ng/dL, so your levels represent only partial suppression 1
• The loss of nocturnal erections you're experiencing indicates some androgen blockade, but your serum testosterone confirms inadequate suppression for full feminization 3

Why Your Current Regimen Is Ineffective

Oral estradiol 3 mg daily is a relatively low dose that frequently fails to achieve adequate testosterone suppression, even when combined with spironolactone. 4

• Research demonstrates that over 70% of transgender women require at least 4 mg daily of oral estradiol to achieve treatment goals, and nearly one-third fail to suppress testosterone adequately even on 6-8 mg daily 4
• Spironolactone does not reliably enhance testosterone suppression despite being marketed as an antiandrogen - studies show it may actually impair achievement of target estradiol levels without providing additional testosterone lowering 4, 5
• Your dose of spironolactone (up to 200 mg daily) is at the upper end of typical dosing (50-200 mg daily), yet your testosterone remains elevated 3, 1

Tissue Changes and Reversibility

The penile tissue changes that occur with hormone therapy exist on a spectrum from reversible to permanent, depending on duration and degree of testosterone suppression.

• Loss of nocturnal erections leads to decreased oxygenation of erectile tissue, which can cause some tissue atrophy over time 3
• However, without adequate testosterone suppression to female levels (<50 ng/dL), significant permanent structural changes are unlikely 1, 2
• If testosterone suppression were adequate and maintained for 12-24 months with complete absence of erections, more permanent changes would be expected 2

Clinical Implications

Your inadequate testosterone suppression means you are likely not achieving the full feminizing effects you may be seeking, while experiencing some side effects from the medications.

• Target testosterone levels should be <50 ng/dL for effective feminization, with estradiol levels in the cisgender female reference range (typically 100-200 pg/mL) 1, 2, 6
• Transdermal estradiol (patches 50-100 μg/24 hours) achieves more rapid and effective testosterone suppression compared to oral formulations and carries lower cardiovascular risk 2, 6, 7
• Recent randomized controlled trial data shows transdermal estradiol suppresses testosterone more effectively with lower overall estradiol doses compared to sublingual or oral routes 6

Common Pitfalls to Avoid

• Do not assume spironolactone is effectively blocking androgens based on side effects alone - serum testosterone levels are the definitive measure 4, 5
• Oral estradiol has high individual variability in absorption and may require doses of 6-8 mg daily or higher, which increases cardiovascular risk 4
• Continuing inadequate therapy delays achieving feminization goals while exposing you to medication side effects without full benefit 1, 2

Monitoring Recommendations

Hormone levels should be checked every 3-6 months during the first year to ensure adequate suppression and adjust dosing accordingly. 1, 2

• Measure trough testosterone (target <50 ng/dL) and estradiol levels (target 100-200 pg/mL, though recent evidence questions rigid adherence to this range) 1, 2
• After 12 months on adequate hormone therapy, laboratory reference ranges should shift to female values for parameters including creatinine, hemoglobin, and liver enzymes 1