Praxis Medical Insights

Est. 2024 • Clinical Guidelines Distilled

Made possible by volunteer editors from the University of Calgary & University of Alberta

Last Updated: 9/7/2025

Gender Affirming Hormone Therapy Protocol

Initial Assessment and Therapy Protocol

  • The American College of Physicians recommends a comprehensive baseline assessment, including complete blood count, liver function tests, lipid profile, glucose levels, and baseline hormone levels, before initiating gender-affirming hormone therapy (GAHT) 2
  • Fertility preservation counseling must be provided before starting hormone therapy, as both feminizing and masculinizing treatments may affect fertility 2
  • Estradiol is the cornerstone of feminizing hormone therapy, available in oral, transdermal, or injectable forms, and anti-androgens are typically added to enable lower doses of estrogen while achieving adequate testosterone suppression 1, 2

Feminizing Hormone Therapy

  • Target testosterone levels should be <50 ng/dL, and target estradiol levels should be in the cisgender female reference range, with monitoring every 3-6 months during the first year, then annually if stable 1, 2
  • Breast development, decreased muscle mass, softening of skin, decreased body/facial hair, decreased libido, and reduced erectile function are expected physical changes 1, 2
  • Hemoglobin levels decrease to the female reference range 4, 5

Masculinizing Hormone Therapy

  • Testosterone therapy is used to induce virilization and suppress feminizing characteristics, with standard doses aiming to achieve serum testosterone concentrations in the typical cisgender male reference range (300-1,000 ng/dL) 2, 3
  • Haemoglobin will increase to the male reference range within 3 months, and monitoring of testosterone levels should occur every 3-6 months during the first year, then annually if stable 2, 3
  • Thicker vocal cords producing a deeper voice pitch, body and facial hair growth, menstrual suppression, increased libido, and clitoral growth are expected physical changes 3

Laboratory Value Interpretation

  • For individuals on GAHT for ≥12 months, interpret lab values within reference range for affirmed gender, and for those on GAHT for <12 months, interpret values in context of type, dose, and duration of GAHT 4, 5
  • Red blood cell indices, liver enzymes, electrolytes, and creatinine are significantly influenced by GAHT, and troponin and PSA should use reference ranges from sex assigned at birth 4, 5

Potential Side Effects and Management

  • Feminizing therapy risks include increased risk of venous thromboembolism, ischemic stroke, and myocardial infarction, as well as weight gain and potential compromised bone structure 1, 2
  • Masculinizing therapy risks include erythrocytosis, increased blood pressure, elevated triglycerides and LDL cholesterol, decreased HDL cholesterol, acne, androgenic alopecia, and pelvic pain 2, 3, 6

Special Populations

  • Puberty blockers (GnRH analogues) can be used in early puberty to suppress testosterone and estradiol, and have been shown to reduce suicidality and improve psychological function in adolescents 3

Monitoring Algorithm

  • Baseline assessment before starting therapy, checking hormone levels at 3 months, monitoring every 3-6 months during the first year, and annual monitoring once stable are recommended 1, 2