What is the appropriate evaluation and management for a 27‑year‑old transgender woman who complains of pain only during erection?

Pain During Erection in a 27-Year-Old Transgender Woman

Stop spironolactone immediately and switch to an alternative anti-androgen (leuprolide or bicalutamide) or increase estradiol to monotherapy doses, as spironolactone directly causes genital tissue atrophy leading to painful erections in transgender females. 1, 2

Understanding the Mechanism

The pain this patient experiences is a direct physiological consequence of genital tissue atrophy caused by spironolactone. 1 This anti-androgen decreases testosterone production, competitively blocks androgen receptors, inhibits 5-alpha-reductase, and increases steroid hormone-binding globulin—all contributing to significant genital tissue changes that manifest as pain during erection or sexual activity. 1, 2

Immediate Management Algorithm

Step 1: Discontinue Spironolactone

• Stop spironolactone immediately—any dose can cause this complication, and continuing it will prevent resolution of the underlying atrophy. 1, 2
• Do not discontinue all hormone therapy, as this will worsen gender dysphoria and overall quality of life. 1, 2

Step 2: Choose Alternative Anti-Androgen Strategy

Option A: Switch to GnRH Agonist (Preferred)

• Leuprolide directly suppresses testosterone production at the hypothalamic-pituitary axis without causing genital atrophy side effects. 1, 2

Option B: Switch to Peripheral Androgen Receptor Antagonist

• Bicalutamide avoids the genital atrophy issues associated with spironolactone. 1, 2
• Monitor liver function tests regularly due to potential hepatotoxicity. 1

Option C: Estradiol Monotherapy

• If the patient's current estradiol dose is subtherapeutic (typical feminizing doses are significantly higher), consider increasing estradiol to achieve both feminization and testosterone suppression. 1
• Higher doses of estradiol alone can suppress testosterone through negative feedback on the pituitary-gonadal axis. 2
• Monitor estradiol levels to ensure they remain in the cisgender female reference range (typically 100-200 pg/mL). 1

Evaluation of the Pain

History Taking

• Use the patient's preferred terminology when discussing anatomy to reduce psychological distress. 1, 2
• Assess timing: when did pain start relative to hormone therapy initiation? 1
• Characterize the pain: severity, quality, associated symptoms. 3
• Screen for sexually transmitted infections if sexually active, particularly urethritis from gonorrhea or chlamydia. 1, 2

Physical Examination

• Obtain explicit permission before any genital examination and allow the patient to guide the examination to maintain control. 1, 2
• Perform focused examination evaluating the penis and testicles for signs of atrophy, dermatologic conditions (such as lichen sclerosus), or infection. 3, 1

Laboratory Assessment

• Check testosterone levels at 3 months after switching therapy to ensure adequate suppression below 50 ng/dL. 1, 2
• Monitor estradiol levels to ensure therapeutic range. 1, 2
• Test for gonorrhea and chlamydia if sexually active. 1, 2

Monitoring and Follow-Up

• Reassess pain levels and genital tissue appearance at 4-6 weeks after stopping spironolactone and starting alternative therapy. 1, 2
• Continue monitoring hormone levels every 3-6 months during the first year after the switch, then annually if stable. 1
• Gender identity plays a more significant role in pain sensation than sex assigned at birth, and affirming care improves pain outcomes. 1, 2, 4

Critical Pitfalls to Avoid

• Never continue spironolactone while attempting symptomatic treatment—the underlying cause must be removed. 1, 2
• Do not undertreat pain in transgender patients, as there is documented bias and undertreatment in this population. 1, 2
• Never use ethinyl estradiol as an alternative estrogen due to significantly higher thrombotic risk compared to bioidentical estradiol. 1, 2
• Do not make assumptions about sexual activity or practices—obtain a thorough sexual history in a nonjudgmental manner. 3

Psychosocial Considerations

• Screen for comorbid anxiety, depression, and substance use, which are more prevalent in transgender populations and affect pain management. 1, 2
• Transgender persons are impacted by sexual assault at higher rates than cisgender persons, which can contribute to chronic pain syndromes. 1
• Consider referral to a trauma specialist if there is a history of sexual violence or significant psychological distress. 1
• Sexual dysfunction is common in transgender individuals during transition, and addressing this proactively improves quality of life. 5, 6