What is the recommended treatment approach for individuals experiencing gender incongruence?

Treatment Approach for Gender Incongruence

Individuals experiencing gender incongruence should receive multidisciplinary team-based care that includes mental health assessment, psychosocial support, and—when appropriate—gender-affirming hormone therapy and surgical interventions, with treatment decisions guided by the patient's experienced gender identity rather than assigned sex at birth. 1

Core Treatment Framework

The treatment approach must involve a specialized multidisciplinary team that includes:

• Endocrinologist for hormone management 1
• Mental health professional (psychologist/psychiatrist) for assessment and ongoing support 1, 2
• Primary care physician for general health monitoring 2
• Surgeon experienced in gender-affirming procedures (when surgical intervention is considered) 1
• Social work and nursing support when available 1

This team-based approach ensures comprehensive evaluation, informed decision-making, and coordinated care throughout the gender affirmation process. 1

Mental Health Assessment and Psychosocial Support

All patients require initial mental health evaluation to confirm gender dysphoria/incongruence, assess readiness for treatment, and identify co-existing mental health conditions. 2, 3

• Mental health professionals must be knowledgeable about diagnostic criteria for gender dysphoria and have sufficient training in assessing psychopathology. 2
• Ongoing counseling and psychosocial support should continue throughout treatment, as gender affirmation is a long-lasting process. 1, 4
• Critical pitfall: Dissociative identity disorder and other complex psychiatric conditions can present with symptoms that mimic gender incongruence—careful assessment is essential to avoid inappropriate treatment. 5, 3
• Depression, anxiety, autism spectrum disorders, and eating disorders commonly co-occur and require individualized management. 1, 3

Hormone Therapy for Adolescents

For adolescents who have entered puberty (Tanner Stage G2/B2), treatment begins with GnRH agonists (puberty blockers) to suppress endogenous sex hormone production. 2

• GnRH analogues directly suppress FSH and LH production, effectively halting testosterone or estrogen production at the hypothalamic-pituitary level. 6
• Gender-affirming hormones may be added after the multidisciplinary team confirms persistence of gender dysphoria and the patient demonstrates sufficient mental capacity for informed consent—typically by age 16 years. 2
• Compelling reasons may justify initiating sex hormone treatment prior to age 16, though minimal published experience exists for treatment before 13.5-14 years of age. 2

Hormone Therapy for Transgender Females (Male-to-Female)

Estradiol is the cornerstone of feminizing therapy, available in oral, transdermal, or injectable forms, combined with anti-androgen therapy to suppress testosterone. 6

Estrogen Regimen:

• Target estradiol levels should be maintained in the cisgender female reference range. 6
• Physical changes include breast development, decreased lean body mass (3.0-5.5% reduction), skin softening, decreased body/facial hair, and significant decreases in hemoglobin levels. 6
• Muscle changes include 5% decrease in thigh muscle volume and 4% decrease in quadriceps cross-sectional area. 6

Anti-Androgen Options:

• Spironolactone is the most commonly used anti-androgen in many countries. 6
• Alternative options include cyproterone acetate, GnRH agonists, bicalutamide, and finasteride. 6
• Target testosterone levels should be <50 ng/dL. 6

Monitoring Protocol:

• Baseline assessment: Complete blood count, liver function, lipid profile, glucose, and baseline hormone levels. 6
• Initial follow-up at 3 months to check estradiol and testosterone levels. 6
• Ongoing monitoring every 3-6 months during the first year, then annually if stable. 6

Critical Cardiovascular Risks:

• Transgender women have significantly increased risk of venous thromboembolism compared to both cisgender men and women. 6
• Elevated risk of ischemic stroke and myocardial infarction exists and requires individualized risk assessment. 6
• Avoid ethinyl estradiol, which increases VTE risk more than other estrogen formulations. 6

Hormone Therapy for Transgender Males (Female-to-Male)

Testosterone therapy is administered via intramuscular or subcutaneous injection of testosterone cypionate or enanthate, targeting serum testosterone concentrations of 300-1,000 ng/dL. 7

Testosterone Regimen:

• Maintain trough testosterone levels between 300-1,000 ng/dL, targeting the mid-normal range to optimize safety and efficacy. 7
• Hemoglobin will increase to the male reference range within 3 months of starting therapy. 7

Expected Physical Changes:

• Deepening of voice due to thickened vocal cords. 7
• Facial and body hair growth. 7
• Menstrual suppression (achieved in most patients). 7
• Clitoral growth, increased muscle mass, decreased fat mass, and increased libido. 7

Critical Monitoring Parameters:

• Monitor for erythrocytosis/polycythemia, particularly common with injectable formulations—consider switching to transdermal route if it develops. 7
• Monitor blood pressure, as testosterone may increase blood pressure. 7
• Check lipid profiles regularly, as testosterone may increase triglycerides and LDL cholesterol while decreasing HDL. 7

Common Adverse Effects:

• Avoid supraphysiologic dosing, which increases risk of adverse effects without additional benefit. 7
• Androgenic alopecia and acne are common. 7
• Gynecological effects including pelvic pain and genital dryness may occur. 7
• Reduced HDL cholesterol and potential increased risk of myocardial infarction. 7

Surgical Considerations

Gender-affirming surgery should only be performed after confirmation of persistent gender dysphoria by the multidisciplinary team and demonstration of informed consent capacity. 1, 2

• The treating physician must collaborate with and confirm the criteria for treatment used by the referring mental health practitioner. 2
• Decisions regarding surgical intervention are not directly linked to gender assignment decisions and should consider diagnosis, genital appearance, potential fertility, therapeutic requirements, and familial/cultural factors. 1
• When natal gonads are surgically removed, sex steroid treatment doses may be reduced. 2
• Monitor for reproductive organ cancer risk when surgical removal is incomplete. 2

Special Considerations and Pitfalls

Gender identity cannot be reliably predicted by clinical data, including degree of genital masculinization or prenatal androgen exposure. 1

• Up to 25% of individuals may develop signs of gender dysphoria over time, even with appropriate gender assignment. 1
• The interaction between prenatal androgens and multiple postnatal factors in determining gender identity is highly complex and variable. 1
• Use correct pronouns and terminology (she/her for trans women, he/him for trans men, they/them for non-binary individuals) to demonstrate inclusivity and provide better healthcare. 1
• Gender dysphoria describes psychological distress from gender incongruence—not all transgender individuals experience dysphoria. 1
• Avoid treating individuals who have conditions other than gender dysphoria/incongruence, as they may not benefit from physical changes associated with hormone treatment. 2