The Journal of Clinical Endocrinology & Metabolism (JCEM)Approach to the Patient: Pharmacological Management of Trans and Gender-Diverse Adolescents

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Current clinical evidence supports the use of pharmacological interventions for transgender and gender-diverse (TGD) adolescents, with options including pubertal suppression (PS), modulation of endogenous pubertal hormone effects, and gender-affirming hormone (GAH) therapy. Although short-term outcomes are encouraging, particularly regarding mental health improvements, longer-term prospective data remains limited. This article presents current treatment approaches, clinical considerations, and emerging evidence to guide physician decision-making in the care of TGD youth.

Key Points:

• Pharmacological Options:
  • GnRH agonists (GnRHa) for pubertal suppression
  • Antiandrogens (cyproterone acetate, spironolactone) for androgen effect modulation
  • Progestogens for menstrual suppression
  • 17β-estradiol for feminization
  • Testosterone for masculinization
• Mental Health Outcomes:
  • Most studies report improved psychological functioning post-hormonal therapy
  • Decreased rates of depression, self-harm, and suicidal ideation
  • No significant change in gender dysphoria with PS alone
  • Significant improvements in body satisfaction with GAH
• Clinical Monitoring Requirements:
  • Bone mineral density during PS
  • Electrolytes with spironolactone
  • Liver function with cyproterone acetate
  • Hematocrit and lipids with testosterone
  • Prolactin with estrogen therapy
  • Blood pressure and cardiovascular risk factors
• Safety Considerations:
  • Low regret rates reported (0.5% in adults, 0% in those presenting <18 years)
  • Fertility preservation counseling essential before treatment
  • Some effects irreversible (voice changes, breast development)
  • Impact on bone health requires monitoring
  • Limited long-term safety data in adolescent population

In a 2022 study of a prospective cohort of 104 TNB youths aged 13 to 20 years, receipt of gender-affirming care, including puberty blockers and gender-affirming hormones, was associated with 60% lower odds of moderate or severe depression and 73% lower odds of suicidality over a 12-month follow-up. (JAMA Network Open)

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