In a 19‑year‑old transgender woman (assigned male at birth) with baseline male‑range total testosterone, thick facial hair, and normal erectile function, who is on estradiol and spironolactone and now has fluctuating testosterone levels with loss of nocturnal erections, how should anti‑androgen therapy be adjusted to achieve consistent testosterone suppression while preserving desired sexual function?

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Optimizing Anti-Androgen Therapy for Consistent Testosterone Suppression While Preserving Sexual Function

Direct Recommendation

Increase spironolactone to 100 mg twice daily (200 mg total daily) and consider switching to cyproterone acetate 25 mg daily or adding a GnRH agonist if testosterone remains above 50 ng/dL, as spironolactone monotherapy frequently fails to achieve adequate testosterone suppression even at higher doses. 1, 2, 3

Understanding Your Current Situation

Your testosterone levels have been inconsistent (316 → 437 → 180 ng/dL) despite escalating therapy, and you've lost nocturnal erections—a sign of inadequate androgen activity for maintaining that specific function. 1 The target testosterone level for feminizing hormone therapy is <50 ng/dL, which you have not consistently achieved. 1, 2

  • Your current regimen (estradiol 3 mg daily + spironolactone 100 mg daily) is insufficient, as evidenced by testosterone of 180 ng/dL—well above the therapeutic target. 1, 2
  • The "rebound" to 437 ng/dL when spironolactone was added at low dose (25 mg daily) reflects inadequate anti-androgen effect. 4, 5
  • Loss of nocturnal/morning erections indicates testosterone has dropped enough to impair this androgen-dependent function, but not low enough to meet feminization goals. 1

Why Spironolactone Is Failing You

Spironolactone is the weakest anti-androgen option and frequently cannot suppress testosterone to female range even at maximum doses. 4, 5, 3

  • In a randomized trial, only 19% of transgender women on spironolactone 100 mg daily achieved testosterone <50 ng/dL, compared to 90% on cyproterone acetate 25 mg daily. 3
  • A 2018 study found spironolactone did not enhance testosterone suppression and actually impaired achievement of target estradiol levels. 4
  • A 2025 study confirmed spironolactone was not associated with additional testosterone suppression beyond estradiol monotherapy and resulted in lower estradiol levels. 5
  • Your dose of 100 mg daily is at the lower end of the typical range (100-300 mg daily), but even higher doses often fail. 2

Algorithmic Approach to Adjusting Therapy

Step 1: Optimize Current Spironolactone Dose (If Staying on Spironolactone)

  • Increase to 200 mg daily (100 mg twice daily) as an immediate step. 2
  • Recheck testosterone and estradiol levels at 3 months. 1, 2
  • If testosterone remains >50 ng/dL, proceed to Step 2. 1, 2

Step 2: Switch to a More Effective Anti-Androgen

Cyproterone acetate 25 mg daily is the most effective option for testosterone suppression:

  • Achieves female-range testosterone (<50 ng/dL) in 90% of patients vs. 19% with spironolactone. 3
  • Significantly greater testosterone reduction (558 ng/dL drop vs. 226 ng/dL with spironolactone). 3
  • Caution: Monitor liver enzymes (risk of drug-induced liver injury) and prolactin (risk of hyperprolactinemia). 3

Alternative: GnRH agonist (puberty blocker) if cyproterone is unavailable or contraindicated:

  • Directly suppresses FSH and LH at the hypothalamic-pituitary level, halting testosterone production at its source. 2
  • Most reliable method for achieving testosterone <50 ng/dL. 1, 2
  • Does not carry the hepatotoxicity risk of cyproterone. 3

Bicalutamide is another option but acts peripherally as an androgen receptor antagonist without lowering testosterone levels, so it won't help you achieve the target testosterone <50 ng/dL. 2

Step 3: Consider Increasing Estradiol Dose

  • Your current estradiol dose (3 mg daily oral) is at the lower end of the typical range (2-6 mg daily). 1
  • Increasing to 4-6 mg daily may improve testosterone suppression, as higher estradiol doses correlate with better testosterone suppression. 4, 5
  • However, oral estradiol alone frequently cannot achieve adequate testosterone suppression even at 6-8 mg daily. 4
  • Injectable estradiol (estradiol valerate or cypionate) may be more effective: a 2025 study showed excellent testosterone suppression with injectable estradiol at doses as low as 3.7 mg weekly. 5

Addressing Sexual Function Concerns

Preserving erectile function while achieving feminization goals is extremely difficult because the two are physiologically opposed. 1

  • Nocturnal/morning erections are androgen-dependent and typically lost when testosterone drops below ~200-300 ng/dL. 1
  • Your target testosterone (<50 ng/dL) is incompatible with maintaining spontaneous erections. 1, 2
  • You can still achieve erections with PDE5 inhibitors (sildenafil, tadalafil) even at low testosterone levels, but spontaneous/nocturnal erections will not return. 1

If preserving spontaneous erectile function is a priority:

  • You would need to maintain testosterone >200 ng/dL, which conflicts with feminization goals and is not consistent with standard feminizing hormone therapy. 1, 2
  • This is a trade-off you must explicitly discuss with your provider, as it represents a deviation from standard care. 1

Monitoring Plan

  • Recheck testosterone and estradiol at 3 months after any dose adjustment or medication change. 1, 2
  • If switching to cyproterone acetate, monitor liver enzymes and prolactin at baseline and 3 months. 3
  • Once testosterone is consistently <50 ng/dL, monitor every 3-6 months for the first year, then annually. 1, 2

Critical Pitfalls to Avoid

  • Do not assume spironolactone will eventually work at higher doses—the evidence shows it is ineffective for most patients. 4, 5, 3
  • Do not expect to maintain spontaneous erections while achieving testosterone <50 ng/dL—these goals are mutually exclusive. 1
  • Do not use finasteride as your primary anti-androgen—it is associated with higher testosterone levels, not lower. 4
  • Do not neglect cardiovascular risk assessment—transgender women on estradiol have increased risk of venous thromboembolism, stroke, and myocardial infarction. 1, 2
  • Do not fail to counsel about permanent genital changes—penile shrinkage and testicular atrophy are expected and may be irreversible, which can affect future vaginoplasty if desired. 1

References

1
Guideline

Hormone Therapy for Male to Female Gender Affirming Care

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Hormone Management for Transgender Females

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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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?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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