What hormone replacement therapy (HRT) options are available for a transgender female patient assigned male at birth with a family history of prostate cancer and currently taking Adderall XR (amphetamine and dextroamphetamine)?

Hormone Replacement Therapy for Transgender Female with Family History of Prostate Cancer on Adderall XR

Direct Recommendation

Initiate feminizing hormone therapy with estradiol (oral 2-6 mg daily, transdermal 0.1-0.4 mg/day, or injectable 5-20 mg IM every 1-2 weeks) combined with spironolactone (100-300 mg daily) as the anti-androgen, with the family history of prostate cancer being a relative indication FOR rather than against hormone therapy, and no contraindication exists with concurrent Adderall XR use. 1, 2, 3

Rationale for Prostate Cancer Family History

• A family history of prostate cancer does not contraindicate feminizing hormone therapy and may actually be protective, as estrogen therapy suppresses testosterone—the primary driver of prostate cancer growth—to castrate levels (<50 ng/dL). 1, 3

• Estradiol is FDA-approved for palliative treatment of advanced androgen-dependent carcinoma of the prostate, demonstrating its therapeutic role in suppressing prostate tissue stimulation. 4, 5

• The goal of feminizing hormone therapy includes suppressing testosterone to <50 ng/dL, which is the same target used in medical castration for prostate cancer treatment. 1, 2, 3

Core Hormone Therapy Regimen

Estradiol Options

• Estradiol is the cornerstone medication available in three formulations: oral tablets (2-6 mg daily), transdermal patches (0.1-0.4 mg/day), or injectable estradiol valerate/cypionate (5-20 mg IM every 1-2 weeks). 1, 2, 3

• Avoid ethinyl estradiol, which carries significantly higher thrombotic risk than bioidentical estradiol formulations. 3

• Transdermal estradiol may be preferred if cardiovascular risk factors are present, as it has less impact on hepatic metabolism and clotting factors compared to oral formulations. 1

Anti-Androgen Selection

• Spironolactone (100-300 mg daily) is the first-line anti-androgen in the United States, functioning as an aldosterone receptor antagonist that decreases testosterone production and competitively inhibits androgen receptor binding. 1, 2, 3

• Alternative anti-androgens include cyproterone acetate (not available in US), GnRH agonists, bicalutamide, or finasteride, though spironolactone remains most commonly used. 1, 3

• The combination of estradiol plus anti-androgen enables lower estrogen doses while achieving adequate testosterone suppression, reducing cardiovascular risk. 1, 3

Medication Interaction Assessment

• No documented interactions exist between Adderall XR (amphetamine/dextroamphetamine) and either estradiol or spironolactone, allowing safe concurrent use. 1

• Routine potassium monitoring is unnecessary at typical spironolactone doses (50-200 mg daily) in young healthy individuals, with only 0.75% experiencing potassium >5.0 mmol/L. 1

• Potassium monitoring becomes necessary only if: dose exceeds 200 mg daily, patient takes ACE inhibitors/ARBs/NSAIDs/digoxin, or renal impairment exists. 1

Target Hormone Levels and Monitoring Schedule

Target Levels

• Testosterone: <50 ng/dL (castrate range, same target used in prostate cancer treatment). 1, 2, 3

• Estradiol: within cisgender female reference range (typically 100-200 pg/mL, though specific targets vary by lab). 1, 2, 3

Monitoring Algorithm

• Baseline assessment (before initiating therapy): complete blood count, comprehensive metabolic panel, liver function tests, lipid profile, glucose, baseline testosterone and estradiol levels. 1, 3

• 3-month follow-up: check estradiol and testosterone levels, adjust doses to achieve target ranges. 1, 2, 3

• Every 3-6 months during first year: hormone levels, blood pressure (especially on spironolactone), liver function, lipids. 1, 2, 3

• Annually once stable: hormone levels, cardiovascular risk assessment, bone density consideration after age 60 or if risk factors present. 1, 2, 3

Expected Physical Changes and Timeline

• Breast development: begins within 3-6 months, continues for 2-3 years, with variable outcomes (studies show 9% achieve A cup, 16% B cup). 1, 2

• Body composition changes: 3.0-5.5% reduction in lean body mass, increased body fat in hips/thighs/face, decreased abdominal fat within 3-12 months. 1, 2, 3

• Skin changes: softening and decreased oiliness within 3-6 months. 2, 3

• Hair changes: decreased body and facial hair growth (gradual, ongoing). 3

• Hemoglobin: decreases to female reference range. 1, 3

• Sexual function: decreased libido and reduced erectile function. 3

Cardiovascular Risk Management

• Transgender women have increased risk of venous thromboembolism (VTE) compared to both cisgender men and women, with elevated risk of ischemic stroke and myocardial infarction. 1, 2, 3

• This thrombotic risk is dose-dependent and persists despite changes in estradiol preparations over time, requiring individualized risk assessment. 1

• Monitor blood pressure closely, particularly on spironolactone which can cause diuresis (29% of patients) but also has antihypertensive effects. 1, 2

• Consider more frequent cardiovascular monitoring if pre-existing risk factors (hypertension, diabetes, smoking, obesity, family history of cardiovascular disease) are present. 3

Prostate Cancer Screening Considerations

• Continue age-appropriate prostate cancer screening despite feminizing hormone therapy, as transgender women retain prostatic tissue. 6

• The family history of prostate cancer warrants discussion about screening, though testosterone suppression to castrate levels significantly reduces prostate cancer risk. 6

• PSA levels will decrease on feminizing hormone therapy due to testosterone suppression, requiring interpretation in the context of hormone therapy. 6

Common Pitfalls to Avoid

• Failing to provide fertility preservation counseling before initiating therapy, as hormone therapy may permanently impair fertility. 2, 3

• Using ethinyl estradiol instead of bioidentical estradiol, which significantly increases VTE risk. 3

• Inadequate monitoring during the first year, when dose adjustments are most frequently needed. 1, 2, 3

• Overlooking cardiovascular risk stratification before initiating therapy, particularly important given elevated VTE and cardiovascular risks in transgender women. 1, 2, 3

• Misinterpreting laboratory values: after >1 year on hormone therapy, lab values should generally be interpreted based on affirmed gender (female reference ranges). 3

• Assuming family history of prostate cancer is a contraindication when it is actually neutral to potentially protective given testosterone suppression. 6, 4, 5

Additional Supportive Care

• Mental health support during transition improves outcomes, as gender-affirming hormone therapy has been shown to improve quality of life, reduce gender dysphoria, and improve psychological functioning. 2

• Calcium (1500 mg/day) and vitamin D (400-800 IU/day) supplementation should be considered for bone health, particularly with long-term hormone therapy. 4, 5

• Weight-bearing exercise should be encouraged to maintain bone density and cardiovascular health. 4, 5