What treatment options are available for gender affirming care, including hormone replacement therapy (HRT)?

Gender-Affirming Care Treatment Options

Gender-affirming care consists of hormone replacement therapy (HRT) and surgical interventions, with treatment decisions made collaboratively between transgender and gender diverse (TGD) patients and their healthcare team, including primary care physicians, endocrinologists, and mental health professionals. 1

Core Treatment Components

Hormone Replacement Therapy (HRT)

Feminizing Hormone Therapy (for Transgender Women)

• Estradiol is the cornerstone medication, available in oral (2-6 mg daily), transdermal (0.1-0.4 mg/day), or injectable formulations (5-20 mg IM every 1-2 weeks) 2, 3
• Anti-androgens are typically added to suppress testosterone production while enabling lower estrogen doses, with spironolactone (100-300 mg daily) being the most common option 2
• Target hormone levels: testosterone <50 ng/dL and estradiol in the cisgender female reference range 4, 2
• Expected physical changes include breast development, decreased muscle mass (3.0-5.5% reduction in lean body mass), softening of skin, decreased body/facial hair, decreased libido, reduced erectile function, and hemoglobin decreasing to female reference range 2

Masculinizing Hormone Therapy (for Transgender Men)

• Testosterone is the primary medication administered intramuscularly, with doses aimed at achieving serum testosterone concentrations in the typical cisgender male reference range (300-1,000 ng/dL) 4, 5
• Hemoglobin increases to male reference range within 3 months of initiating therapy 4
• Expected physical changes include deeper voice pitch from thicker vocal cords, body and facial hair growth, menstrual suppression, increased libido, and clitoral growth 4

Gender-Affirming Surgeries

Surgical options vary based on individual needs and may include: 1

• Chest procedures: chest masculinization (top surgery) for transgender men or breast augmentation for transgender women 1
• Genital surgeries: gonadectomy (bilateral oophorectomy or orchiectomy) and other genital reconstruction procedures 1
• Facial/neck procedures: including vocal pitch-raising procedures 6

Treatment Initiation Protocol

Pre-Treatment Assessment

Complete baseline evaluation must include: 4, 2

• Complete blood count, liver function tests, lipid profile, glucose levels, and baseline hormone levels 4
• Fertility preservation counseling is mandatory before starting hormone therapy, as both feminizing and masculinizing treatments may affect fertility 4, 2
• Mental health evaluation and confirmation of diagnostic criteria for gender dysphoria/gender incongruence 1, 7

Monitoring Schedule

Follow a structured monitoring algorithm: 4, 2

• Check hormone levels at 3 months after initiating therapy 4, 2
• Monitor every 3-6 months during the first year 4, 2
• Annual monitoring once hormone levels are stable 4, 2

Health Outcomes and Benefits

Research demonstrates that when TGD persons receive medically appropriate gender-affirming care, they experience: 1

• Improved mental health 1
• Reduction in suicide rates 1
• Lower overall healthcare costs due to fewer mental health-related and substance abuse-related costs 1

Important Risks and Monitoring Requirements

Feminizing Therapy Risks

Cardiovascular and thrombotic complications require vigilant monitoring: 2

• Increased risk of venous thromboembolism 2
• Increased risk of ischemic stroke and myocardial infarction 2
• Weight gain and potential compromised bone structure 2

Masculinizing Therapy Risks

Metabolic and hematologic complications necessitate regular surveillance: 4

• Erythrocytosis (polycythemia) significantly increasing cardiovascular risk 6, 4
• Increased blood pressure 4
• Elevated triglycerides and LDL cholesterol, decreased HDL cholesterol 4
• Acne, androgenic alopecia, and pelvic pain 4

Laboratory Value Interpretation

For patients on GAHT ≥12 months, interpret laboratory values using reference ranges for affirmed gender 6, 4

Critical exceptions where sex assigned at birth reference ranges should be used: 1, 6

• Cardiac troponin (heart size influences reference values) 1
• PSA in transgender women (though upper limit of normal should be lowered to 1.0 ng/mL when testosterone is suppressed) 1

Special Populations

Adolescents

For gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2: 7

• Suppression with gonadotropin-releasing hormone agonists (puberty blockers) is recommended 7
• Gender-affirming hormones may be added after a multidisciplinary team confirms persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent 7
• Most adolescents have this capacity by age 16 years old, though compelling reasons may exist to initiate treatment prior to age 16 7

Critical Pitfalls to Avoid

Common clinical errors that compromise care quality: 6, 2

• Failing to provide comprehensive baseline assessment before initiating therapy 2
• Not monitoring hormone levels regularly, especially during the first year 2
• Overlooking cardiovascular risk factors that may be exacerbated by hormone therapy 2
• Assuming absence of organs based on gender presentation rather than directly documenting surgical history 6
• Attributing all mental health symptoms to gender identity rather than evaluating for independent psychiatric conditions 6
• Using ethinyl estradiol, which carries higher thrombotic risk than other estrogen formulations 2

Perioperative Considerations

Gender-affirming hormone therapy should be continued throughout the perioperative period unless specific contraindications exist 6

Anatomic considerations affecting emergency procedures: 6

• Patients with cricothyroid approximation surgery may no longer have an accessible cricothyroid membrane, making standard emergency front-of-neck airway impossible 6
• Avoid airway instrumentation for 8-12 weeks following vocal pitch-raising procedures unless absolutely necessary 6