What is the best course of action for a 23-year-old transgender female experiencing pain during erections while taking progesterone, estradiol, and spironolactone?

Management of Painful Erections in a Transgender Female on Hormone Therapy

The most likely cause of pain during erections in this patient is spironolactone-induced genital tissue atrophy, and the recommended approach is to discontinue spironolactone and initiate topical estradiol/testosterone gel to the affected area while maintaining feminizing therapy with estradiol alone or switching to an alternative anti-androgen. 1

Understanding the Problem

Spironolactone's Role in Genital Pain

• Spironolactone functions as a potent anti-androgen by decreasing testosterone production and competitively inhibiting androgen receptor binding, but this mechanism can cause significant genital tissue atrophy 2
• Clinical evidence demonstrates that spironolactone causes vulvar vestibular atrophy and tenderness in individuals with genital tissue, leading to dyspareunia and sexual dysfunction 1
• The anti-androgenic effects of spironolactone deprive genital tissues of necessary androgens for maintaining tissue health, resulting in atrophy that manifests as pain during erection or sexual activity 1

Why This Matters for Transgender Women

• While spironolactone is commonly used in feminizing hormone therapy, its sexual side effects are poorly documented in current literature, creating a knowledge gap that leads to underrecognition of this problem 1
• Gender-affirming hormone therapy can create new pain in individuals who had no pain before, and hormones have important effects on pain processing 3

Immediate Management Steps

Discontinue Spironolactone

• Stop spironolactone immediately, as continuation will perpetuate the genital tissue atrophy causing the pain 1
• All documented cases showed significant improvement after stopping spironolactone, with resolution of pain and improved sexual function 1

Initiate Topical Hormone Therapy

• Apply compounded estradiol 0.01%/testosterone 0.1% gel to the affected genital area twice daily to reverse the atrophy 1
• This topical treatment provides local tissue support without significantly affecting systemic hormone levels or feminization goals 1
• Expect improvement in tissue health and resolution of pain within weeks of starting topical therapy 1

Maintaining Feminization Without Spironolactone

Alternative Anti-Androgen Options

• Switch to a GnRH agonist (such as leuprolide), which directly suppresses testosterone production at the hypothalamic-pituitary axis without the genital atrophy side effects of spironolactone 2
• Consider cyproterone acetate if available in your region, though monitor for hepatotoxicity and other side effects 2
• Bicalutamide is another peripheral androgen receptor antagonist option that may avoid the genital atrophy issues 2

Estradiol Monotherapy Consideration

• If the patient has been on hormone therapy long enough to achieve adequate testosterone suppression (target <50 ng/dL), consider estradiol monotherapy without an anti-androgen 2
• Higher doses of estradiol alone can suppress testosterone production through negative feedback on the pituitary-gonadal axis 2
• Monitor testosterone levels every 3 months initially to ensure adequate suppression remains below 50 ng/dL 2

Addressing Pain and Sexual Function

Use Trauma-Informed Examination Techniques

• Obtain explicit permission before any physical examination of the genital area 4
• Allow the patient to guide the examination and maintain control throughout 4
• Use the patient's preferred terminology when discussing anatomy to reduce psychological distress 4, 5

Rule Out Other Causes

• Screen for sexually transmitted infections if the patient is sexually active, particularly urethritis from gonorrhea or chlamydia 5
• Evaluate for dermatologic conditions such as lichen sclerosus, though this is less likely given the temporal relationship with spironolactone use 5
• Consider that gender identity plays a more significant role in pain sensation than sex assigned at birth, and affirming care improves pain outcomes 3, 5

Monitoring and Follow-Up

Short-Term Monitoring

• Reassess pain levels and tissue appearance at 4-6 weeks after stopping spironolactone and starting topical therapy 1
• Check testosterone levels at 3 months to ensure adequate suppression is maintained with the new anti-androgen regimen or estradiol monotherapy 2
• Monitor estradiol levels to ensure they remain in the cisgender female reference range 2

Long-Term Considerations

• Continue topical estradiol/testosterone gel until genital tissue health is fully restored, then reassess need for ongoing use 1
• If the patient desires to maintain erectile function for sexual activity, the alternative anti-androgen approach or estradiol monotherapy will better preserve this function compared to spironolactone 1
• Regular monitoring every 3-6 months during the first year after the medication change, then annually if stable 2

Critical Pitfalls to Avoid

• Never continue spironolactone while attempting to treat the genital pain, as this will prevent resolution of the underlying atrophy 1
• Do not discontinue all hormone therapy, as this will worsen gender dysphoria and overall quality of life 5
• Avoid undertreating pain in transgender patients, as there is documented bias and undertreatment in this population 5
• Do not assume the pain is psychological or related to gender dysphoria without addressing the physiologic cause 3
• Never use ethinyl estradiol as an alternative estrogen due to significantly higher thrombotic risk 4