transgender physiology hormones health outcomes

Handwritten medical student notes on lined paper for MD Physiology exam. Title: "PHYSIOLOGICAL ISSUES IN TRANSGENDER, GENDER NON-CONFORMING & NON-BINARY INDIVIDUALS" written in blue pen heading. Below in neat handwriting: DEFINITIONS: • Transgender: gender identity differs from sex assigned at birth • Gender Non-Conforming (GNC): does not conform to binary male/female norms • Non-Binary: gender identity is neither exclusively male nor female • Cisgender: gender identity aligns with sex recorded at birth • Gender Dysphoria (DSM-5): clinically significant distress from incongruence • Gender Incongruence (ICD-11): replaces "gender dysphoria" in new classification BIOLOGICAL BASIS OF GENDER IDENTITY: • Gender identity = biologic phenomenon, cannot be externally influenced • Twin studies: 40% concordance in identical twins (0% in fraternal) • XY cloacal exstrophy: many assigned female at birth → male gender identity • CAH (XX individuals): male gender identity in 5% (10x general rate) • Complete AIS (XY): nearly all have female gender identity → Brain androgen exposure in utero may influence gender identity NEUROBIOLOGICAL EVIDENCE: • Bed nucleus of stria terminalis (BNST) in hypothalamus → In transgender women: size in female range (independent of hormone tx) • Brain white matter microstructure: → Untreated trans men: more male-typical → Untreated trans women: intermediate between male and female Neat blue ballpoint handwriting, realistic paper texture, no borders

Handwritten medical student notes on lined paper for MD Physiology exam, blue pen. Title underlined: "FEMINIZING HORMONE THERAPY (Transgender Women: Male → Female)" GOALS: Suppress endogenous testosterone + provide exogenous estrogen ESTROGEN THERAPY: • 17β-Estradiol oral: 2–10 mg/day (most common) • Estradiol patch (transdermal): ↓ VTE risk vs oral • Estradiol valerate IM: 5–20 mg every 2 weeks • AVOID ethinyl estradiol → highest VTE risk EXPECTED PHYSICAL CHANGES (3–12 months): • ↓ Facial/body hair • ↓ Libido, ↓ spontaneous erections • ↓ Skin oiliness, ↓ muscle mass • Redistribution of body fat (feminine pattern) • Breast development (peaks ~2 years) ANTIANDROGENS (adjunct): • Spironolactone 100–300 mg/day → aldosterone antagonist + ↓ testosterone Monitor: hyperkalemia, potassium levels • GnRH agonists (leuprolide) → ↓ LH/FSH → ↓ testosterone • Cyproterone acetate (Europe) → risk: ↑ prolactin, meningioma, ↓ lipids MONITORING: • Target: testosterone <50 ng/dL; estradiol <200 pg/mL • Every 3 months (year 1) then every 6–12 months Realistic handwritten notes on lined notebook paper, blue ink, some words underlined, occasional small arrows

Handwritten medical student notes on lined paper, blue and red pen, MD Physiology exam notes. Title underlined in red: "MASCULINIZING HORMONE THERAPY (Transgender Men: Female → Male)" TESTOSTERONE THERAPY: • IM testosterone enanthate/cypionate: 50–200 mg every 2 weeks • Topical testosterone gel (risk of transfer to others) • Subcutaneous pellets EXPECTED CHANGES (mimics male puberty, takes 4–5 years for full effect): • ↑ Body/facial hair, acne • Voice deepening (irreversible) • Clitoromegaly • ↑ Muscle mass, ↓ body fat (male distribution) • Cessation of menses (within months) • ↑ Libido • Vaginal atrophy METABOLIC EFFECTS: • ↑ LDL cholesterol • ↓ HDL cholesterol • ↑ Hematocrit/polycythemia risk • Insulin resistance may occur BONE HEALTH: • Estrogen suppression → ↓ bone mineral density risk • Monitor with DEXA scan • Some estrogen needed for bone health CARDIOVASCULAR: • ↑ Cardiovascular risk with long-term therapy • VTE risk (especially with supraphysiologic doses) CANCER SCREENING: • Retain cervical cancer screening (Pap smear) • Uterine + cervical cancer documented in transgender men • Breast cancer screening if tissue present Realistic handwriting, lined paper, some red underlines for important points

Handwritten medical student notes for MD Physiology, lined paper, blue pen. Title underlined: "PHYSIOLOGICAL COMPLICATIONS OF GENDER-AFFIRMING HORMONE THERAPY" A. CARDIOVASCULAR COMPLICATIONS: • Estrogen → ↑ VTE risk (DVT, pulmonary embolism) - Oral > transdermal in VTE risk - Estrogen stops during acute VTE treatment • Both trans men and women → insulin resistance • Feminizing hormones + risk factors → ↑ CVD + diabetes • ↑ Cardiovascular risk with testosterone (trans men) B. HEMATOLOGICAL: • Testosterone → polycythemia (↑ RBC, ↑ hematocrit) • Estrogen → ↑ clotting factors C. METABOLIC: • Testosterone: ↑ LDL, ↓ HDL • Estrogen: ↓ LDL, ↑ HDL • Both regimens → possible insulin resistance (may be secular trend) • Body fat redistribution D. BONE METABOLISM: • GnRH agonists + puberty blockers → ↓ bone mineral density • Need some sex steroids for bone health • Risk of osteoporosis if hormones inadequate E. REPRODUCTIVE: • Hormone therapy → reduced fertility (may be reversible early) • Surgery → permanent infertility • Fertility preservation OPTIONS: Trans women: sperm cryopreservation BEFORE starting therapy Trans men: oocyte cryopreservation GnRH analogue delay → allows sperm cryopreservation in trans girls F. LIVER: • ↑ Liver enzymes with supraphysiologic doses • Gallstone risk with estrogen Neat blue handwriting, some boxes around key terms, arrows connecting concepts

Handwritten medical student notes on lined paper, blue pen with some red highlights, MD Physiology exam. Title underlined: "MENTAL HEALTH & PSYCHOSOCIAL PHYSIOLOGY + SPECIAL ISSUES" MENTAL HEALTH BURDEN (due to social stigma, NOT gender incongruence per se): • ↑ Anxiety disorders • ↑ Depression • ↑ Suicidality • Discrimination → 1/3 postpone medical care • ↑ HIV risk: 13× greater than general population - 42% transgender women living with HIV in USA - 62% Black transgender women living with HIV PUBERTAL PHYSIOLOGY IN TRANSGENDER YOUTH: • Puberty blockers (GnRH agonists) → pause "wrong puberty" → Tanner stage 2 ideal timing for intervention → Reversible suppression of sex steroids • Risks of puberty suppression: - ↓ Bone mineral accrual - Unknown long-term neurodevelopmental effects - Potential impact on fertility NON-BINARY PHYSIOLOGY: • May use LOW-DOSE hormones (partial transition) • Goal: neither full male nor full female hormone profile • Even low doses → significant physical changes in some • No known health reasons to prefer male vs female hormone profile SILICONE INJECTION HAZARDS (common in underserved populations): • Immediate: tissue necrosis, silicone embolism → ARDS, organ failure • Early: infected nodules, angioedema • Long-term: silicone granulomas, hypercalcemia, sepsis, organ failure → Up to 50% transgender women may have received illicit injections LAB VALUE INTERPRETATION: • Use reference intervals matching HORMONAL milieu, not chromosomal sex • Testosterone treatment → ↑ LDL, ↓ HDL • Estrogen treatment → ↓ LDL, ↑ HDL • Values shift toward new hormonal milieu over weeks–months Realistic lined paper, neat handwriting, red pen for danger warnings