transgender medicine and hormone therapy

Meet the patient

A 34-year-old transgender woman on oral oestradiol 4 mg and cyproterone acetate 12.5 mg daily for three years presents with acute calf swelling and dyspnoea. She smokes ten cigarettes a day and has a BMI of 32.^[1][3]

The proximal deep vein thrombosis on ultrasound is the oestrogen talking — and the fix is not to abandon her care but to switch the route. A defensible exam answer rests on four pillars:^[1]

1. Confirm the indication and readiness. Adults with persistent, well-documented gender dysphoria may self-refer; adolescents require multidisciplinary assessment, capacity to consent, and (for puberty blockers) Tanner stage 2 or later. Exclude untreated major mental illness and unstable substance use, but do not make therapy contingent on their resolution if gender dysphoria is the dominant distress. ^[1]
2. Choose the safest effective regimen and route. Feminising therapy uses 17-beta oestradiol (preferably transdermal in patients with VTE risk, age over 45, or migraine with aura) plus an anti-androgen (spironolactone first-line, cyproterone acetate at the lowest effective dose under 10 mg daily, or bicalutamide). Masculinising therapy uses parenteral testosterone (undecanoate, enanthate or cypionate) titrated to mid-male reference range. Avoid ethinyl oestradiol (high VTE risk) and oral testosterone (hepatotoxic). ^{[2] [10]}
3. Stratify and mitigate risk. VTE is the dominant early risk of oestrogen (two- to four-fold); use transdermal oestradiol and avoid smoking, obesity and immobilisation. Polycythaemia (haematocrit over 0.52) is the dominant risk of testosterone; dose-adjust or switch to transdermal. Bone mineral density is preserved during suppression-acquired hypogonadism but accrual may lag; reassess and supplement calcium, vitamin D and weight-bearing activity. ^{[3] [8]}
4. Coordinate screening, surgery and primary care. Update cancer screening to align with the organs present (cervical for anyone with a cervix, prostate for anyone with a prostate, breast for transgender women over 50 with more than five years of oestrogen), address cardiovascular risk, HIV pre-exposure prophylaxis when relevant, fertility preservation before GAHT, and a written follow-up plan. ^{[1] [9]}

References12ShowHide

1. [1]Coleman E, Radix AE, Bouman WP, et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 Int J Transgend Health, 2022.PMID 36238954
2. [2]Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab, 2017.PMID 28945902
3. [3]Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones Eur J Endocrinol, 2011.PMID 21266549
4. [4]Quinn VP, Nash R, Hunkeler E, et al. Cohort profile: Study of Transition, Outcomes and Gender (STRONG) to assess health status of transgender people BMJ Open, 2017.PMID 29284718
5. [5]Van Caenegem E, Wierckx K, Taes Y, et al. Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI) Eur J Endocrinol, 2015.PMID 25550352
6. [6]de Blok CJM, Wiepjes CM, Nota NM, et al. Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands BMJ, 2019.PMID 31088823
7. [7]Vlot MC, Klink DT, den Heijer M, et al. Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents Bone, 2017.PMID 27845262
8. [8]Klaver M, de Mutsert R, van der Loos MATC, et al. Hormonal Treatment and Cardiovascular Risk Profile in Transgender Adolescents Pediatrics, 2020.PMID 32102929
9. [9]Radix A, Sevelius J, Deutsch MB Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices J Int AIDS Soc, 2016.PMID 27431475
10. [10]Wierckx K, Mueller S, Weyers S, et al. Long-term evaluation of cross-sex hormone treatment in transsexual persons J Sex Med, 2012.PMID 22906135
11. [11]Miroshnychenko A, Roldan Y, Ibrahim S, et al. Puberty blockers for gender dysphoria in youth: A systematic review and meta-analysis Arch Dis Child, 2025.PMID 39855724
12. [12]Wernick JA, Busa S, Matouk K, et al. A Systematic Review of the Psychological Benefits of Gender-Affirming Surgery Urol Clin North Am, 2019.PMID 31582022