In a 19‑year‑old transgender woman taking oral estradiol 3 mg daily and spironolactone up to 200 mg daily, with serum testosterone fluctuating between approximately 180 ng/dL and 437 ng/dL over several months and loss of nocturnal erections, will this regimen cause permanent penile shortening?

Penile Shrinkage Risk with Suboptimal Testosterone Suppression

Your regimen of oral estradiol 3 mg daily with spironolactone up to 200 mg daily, resulting in testosterone levels of 180-437 ng/dL and loss of nocturnal erections, carries a risk of penile tissue changes, but permanent shrinkage is unlikely at these testosterone levels and duration—the primary issue is inadequate feminizing therapy rather than irreversible genital atrophy.

Understanding the Mechanism

Your testosterone levels remained well above the target of <50 ng/dL throughout treatment, which means you maintained substantial androgenic activity 1, 2. This is critical because:

• Nocturnal erections serve a protective function by maintaining penile tissue oxygenation and preventing fibrosis—their loss can lead to some tissue changes, but this typically requires complete androgen deprivation combined with absence of erectile activity 1
• Your testosterone levels (180-437 ng/dL) represent 30-73% of typical male range (normal male range approximately 300-1000 ng/dL), meaning you retained significant androgenic support 3, 4
• Spironolactone at 200 mg daily should theoretically suppress testosterone to female range (<50 ng/dL), but your levels indicate this regimen was inadequate for you 5, 2

Why Your Regimen Was Suboptimal

The evidence reveals several problems with your treatment approach:

• Oral estradiol 3 mg daily is insufficient for most transgender women—over 70% require 4 mg daily or more to achieve treatment goals, and nearly one-third need 6-8 mg daily 4
• Spironolactone does not reliably enhance testosterone suppression and may actually impair achievement of target estradiol levels 4, 6
• Your fluctuating testosterone levels (180-437 ng/dL) indicate inconsistent suppression, suggesting either inadequate estradiol dosing, poor absorption, or individual variation in response 4, 2

Addressing Permanent Shrinkage Concerns

The likelihood of permanent penile shrinkage in your specific situation is low for these reasons:

• Duration matters: Permanent structural changes typically require years of complete testosterone suppression (<50 ng/dL) combined with complete absence of erectile activity—you had neither 1, 5
• Your testosterone levels remained in a range that provides some tissue maintenance, even without nocturnal erections 4, 5
• Loss of nocturnal erections alone does not guarantee tissue atrophy when testosterone remains partially elevated 5
• Reversibility: Studies show that when testosterone suppression is incomplete (as in your case), tissue changes are generally reversible if hormonal status changes 5

Clinical Context from Studies

Research on transgender women demonstrates:

• Complete testosterone suppression to female range (<50 ng/dL) with spironolactone 200-600 mg daily took 12 months in classic studies, and even then, clinical feminization occurred gradually 5
• Transdermal estradiol achieves testosterone suppression more effectively than oral estradiol, with most transgender women reaching target testosterone levels within 2 months on transdermal therapy 2
• Injectable estradiol at doses of 3.7-4.3 mg weekly achieves excellent testosterone suppression (average 24 ng/dL) without antiandrogens 6

What This Means for You

Your situation represents inadequate feminizing therapy rather than excessive suppression:

• Your testosterone was never adequately suppressed, remaining 3.6-8.7 times higher than the target of <50 ng/dL 1, 2
• The loss of nocturnal erections likely reflects partial androgen blockade from spironolactone's receptor antagonism, not complete testosterone suppression 5
• Any penile tissue changes are more likely related to partial androgen receptor blockade rather than complete tissue atrophy from androgen deprivation 5

Critical Pitfall to Avoid

Do not confuse loss of erectile function with permanent tissue damage—these are distinct phenomena. Loss of nocturnal erections from spironolactone's androgen receptor blockade does not automatically cause irreversible shrinkage, especially when testosterone levels remain elevated 5, 6.

Moving Forward

If you are continuing feminizing therapy, your regimen needs optimization:

• Target testosterone <50 ng/dL consistently, which requires either higher estradiol doses (likely 4-8 mg oral daily) or switching to transdermal/injectable routes 1, 4, 2
• Consider discontinuing spironolactone if adequate estradiol dosing alone can suppress testosterone, as spironolactone may impair estradiol levels without enhancing testosterone suppression 4, 6
• Monitor hormone levels every 3 months until stable, then every 6-12 months 1, 7

If you are concerned about genital preservation for future surgical options, discuss this explicitly with your provider, as maintaining some erectile function through periodic use (with or without aids) may help preserve tissue 1.