In a 19‑year‑old transgender woman receiving estradiol up to 3 mg daily and spironolactone up to 50 mg twice daily, which has lowered serum testosterone to a low level, is this regimen likely to cause permanent penile atrophy (shrinkage)?

Penile Atrophy Risk with Gender-Affirming Hormone Therapy

Your regimen—estradiol up to 3 mg daily with spironolactone up to 100 mg daily for approximately 3 months at testosterone levels around 180–187 ng/dL—carries a moderate to high risk of penile tissue changes, though the permanence and degree of atrophy remain uncertain and likely reversible with consistent erectile function maintenance.

Understanding the Mechanism

The combination of estradiol and antiandrogens works to suppress testosterone production in transgender women, with the goal of achieving testosterone levels below 50 ng/dL 1. Your regimen achieved partial suppression (180–187 ng/dL nadir), which is above the typical female range but well below your baseline 1.

Key Physiological Changes

• Testosterone suppression leads to decreased spontaneous erections (nocturnal and morning erections), which you experienced 1
• Loss of regular erectile activity reduces oxygenation and blood flow to penile tissue, potentially leading to tissue changes over time 1
• Estrogen effects on body composition include decreased lean body mass (3–5.5% reduction) and muscle cross-sectional area changes, though specific penile tissue data are limited 1

Critical Factors in Your Timeline

Testosterone Levels and Duration

Your testosterone levels remained in a partially suppressed range (180–437 ng/dL) for most of your treatment course 1. Notably:

• You spent approximately 3 months with testosterone around 180 ng/dL—this is substantially higher than the target female range of <50 ng/dL 1, 2, 3
• Cyproterone acetate achieves female-range testosterone in 90% of patients, while spironolactone achieves this in only 19% of patients at standard doses 3
• Your spironolactone dosing (25–100 mg daily) was at the lower to moderate end of typical dosing 1, 4

Medication Efficacy Concerns

Spironolactone has limited testosterone-suppression efficacy compared to other antiandrogens 4, 3, 5:

• One study found spironolactone did not enhance testosterone suppression and may impair achievement of target estradiol levels 4
• Cyproterone acetate produces significantly greater testosterone reduction (median drop 558 ng/dL) versus spironolactone (median drop 226 ng/dL) 3
• Nearly one-third of patients on oral estradiol 6–8 mg daily fail to achieve adequate testosterone suppression 4

Protective Factor: Maintained Erectile Function

You maintained volitional erectile function throughout treatment—this is a crucial protective factor 1. Regular erections maintain:

• Penile tissue oxygenation
• Endothelial health
• Tissue elasticity and structure

Evidence on Permanence

The available evidence does not definitively establish permanent penile atrophy from your specific regimen and duration:

• Most transgender medicine literature focuses on feminization effects (breast development, body composition, muscle changes) rather than genital tissue changes 1
• Muscle and tissue changes from feminizing hormone therapy show decreases in lean mass and muscle cross-sectional area, but these studies don't specifically address penile tissue 1
• The 3-month duration at low testosterone is relatively brief compared to years-long hormone therapy regimens typically studied 1

Clinical Interpretation

Lower Risk Factors in Your Case

• Incomplete testosterone suppression (180–187 ng/dL vs. target <50 ng/dL) 1, 2, 3
• Relatively short duration of low testosterone (approximately 3 months) 1
• Preserved erectile function throughout treatment 1
• Testosterone rebound to 437 ng/dL after medication adjustment, showing reversibility 1

Higher Risk Factors

• Loss of spontaneous erections (nocturnal/morning) indicates reduced baseline penile perfusion 1
• Any period of testosterone suppression can initiate tissue changes, though reversibility depends on duration and degree 1

Common Pitfalls to Avoid

Do not assume all tissue changes are permanent—the loss of morning erections reflects hormonal suppression rather than irreversible structural damage, particularly given your maintained volitional function 1.

Spironolactone's limitations are often underappreciated; it may not provide adequate testosterone suppression even at higher doses, and switching to cyproterone acetate or increasing estradiol (particularly transdermal formulations) achieves better suppression 2, 4, 3, 5.

Monitoring testosterone levels is essential—your rebound to 437 ng/dL demonstrates the importance of regular hormone monitoring to ensure consistent suppression if that remains your goal 1, 4.

Practical Recommendations

If you wish to minimize further tissue changes while continuing gender-affirming therapy:

• Consider transdermal estradiol (patches), which achieves more effective testosterone suppression at lower estradiol doses compared to oral formulations 2
• If using antiandrogens, cyproterone acetate 25 mg daily is significantly more effective than spironolactone 100 mg daily for testosterone suppression 3, 5
• Maintain regular erectile function through spontaneous or induced erections to preserve tissue health 1

If you have discontinued or plan to discontinue hormone therapy:

• Testosterone levels typically recover, as evidenced by your rebound to 437 ng/dL 1
• Regular erectile function should help preserve or restore tissue characteristics 1
• The relatively brief duration and incomplete suppression suggest higher likelihood of reversibility 1