What are the guidelines for initiating and monitoring gender affirming medication, including hormone therapy and potential side effects?

Guidelines for Initiating and Monitoring Gender-Affirming Hormone Therapy

Gender-affirming hormone therapy should be initiated with regular monitoring of hormone levels, cardiovascular risk factors, and mental health status to ensure optimal outcomes and minimize adverse effects.

Initial Assessment Before Starting Hormone Therapy

• Comprehensive baseline assessment should include complete blood count, liver function tests, lipid profile, glucose levels, and baseline hormone levels (estradiol and testosterone) 1, 2
• Mental health evaluation is important as transgender individuals have higher rates of psychiatric disorders including anxiety, depression, and autism compared to cisgender individuals 3, 1
• Fertility preservation counseling should be provided before starting hormone therapy, as both feminizing and masculinizing treatments may affect fertility 3, 4

Feminizing Hormone Therapy (Transgender Women)

Medication Options and Dosing

• Estradiol is the cornerstone of feminizing hormone therapy, available in oral, transdermal, or injectable forms 1, 5
• Initial estradiol dosage typically ranges from 1-2 mg daily, adjusted as necessary to control symptoms 5
• Anti-androgens are typically added to enable lower doses of estrogen while achieving adequate testosterone suppression 1
• Common anti-androgen options include:
  • Spironolactone (most commonly used in many countries) 1
  • Cyproterone acetate 1
  • GnRH agonists 1
  • Bicalutamide 1
  • Finasteride 1

Expected Physical Changes and Timeline

• Breast development (variable results: 1% with cup size less than A, 9% with A cup, 16% with B cup) 1
• Decreased muscle mass (5% decrease in thigh muscle volume, 4% decrease in quadriceps cross-sectional area) 1
• Softening of skin, decreased body/facial hair, decreased libido, and reduced erectile function 3
• Changes in body composition with increases in fat mass and reduction in muscle mass 3

Masculinizing Hormone Therapy (Transgender Men)

Medication Options and Dosing

• Testosterone therapy is used to induce virilization and suppress feminizing characteristics 6, 7
• Target testosterone levels should be maintained in the typical physiological range for cisgender men (300-1,000 ng/dL) 6
• Testosterone can be administered via intramuscular injection, transdermal patches, or topical gels 7

Expected Physical Changes and Timeline

• Increased muscle mass and decreased fat mass 6
• Deepening of voice due to thicker vocal cords 3
• Body and facial hair growth 3
• Menstrual suppression 3
• Increased libido and clitoral growth 3

Monitoring Protocol

Short-term Monitoring (First Year)

• Check estradiol and testosterone levels at 3 months after initiating therapy 1
• Monitor every 3-6 months during the first year of hormone therapy 1
• Adjust dosages based on hormone levels and clinical response 1

Long-term Monitoring

• Annual monitoring of hormone levels once stable 1
• Regular cardiovascular risk assessment, as transgender women have an increased risk of venous thromboembolism, ischemic stroke, and myocardial infarction 1
• Monitor hematocrit in transgender men, as testosterone therapy can cause erythrocytosis with hemoglobin typically increasing to the male reference range within 3 months 6

Potential Side Effects and Management

Feminizing Hormone Therapy

• Increased risk of venous thromboembolism, especially with ethinyl estradiol 1
• Weight gain 3
• Compromised bone structure 3
• Cardiovascular disease risk relative to cisgender women and men 3

Masculinizing Hormone Therapy

• Erythrocytosis (elevated hemoglobin and hematocrit) 6
• Increased blood pressure 6
• Elevated triglycerides and LDL cholesterol, decreased HDL cholesterol 6
• Acne, androgenic alopecia, and pelvic pain 3

Special Considerations

• For transgender individuals with pre-existing cardiovascular conditions, more frequent monitoring may be necessary 6
• If erythrocytosis develops in transgender men, consider adjusting the testosterone dose or changing the route of administration 6
• Laboratory values should generally be interpreted based on affirmed gender for individuals on hormone therapy for more than 1 year 6
• Cystatin C may be preferred over creatinine for evaluating kidney function in transgender individuals on hormone therapy 6

Pitfalls and Caveats

• Puberty blockers (GnRH analogues) may cause reduced height velocity and potentially reduced peak bone mass accrual in adolescents 3
• Discontinuation of gender-affirming hormones for fertility treatment can result in partial reversal of physical changes or cessation in the process of gender-affirming physical changes that can worsen dysphoria 3
• Lack of provider training is a major barrier to accessing gender-affirming hormone therapy 8
• Some physical characteristics induced by prior male puberty do not change with feminizing hormone therapy, such as lowered voice pitch, laryngeal prominence, and bone structure 3