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. 2025 May 14;16:1555186. doi: 10.3389/fendo.2025.1555186

Table 4.

Summary of findings.

Outcome Category Key Findings Study Limitations Clinical Implications
Physical Changes & Metabolic Outcomes GnRHa effectively suppresses puberty. Height velocity decreases during treatment, but final height aligns with target height. Changes in body composition observed: increase in fat mass, reduction in lean body mass, and a transient BMI increase in AFAB individuals. Some adolescents report dissatisfaction with final height when it does not align with the average for their affirmed gender. Variability in treatment protocols, GnRHa monotherapy duration, and age at initiation complicates predictions on final height and body composition. Regular monitoring of growth and body composition is necessary. Patients should be counseled about possible height outcomes. Nutritional and physical activity recommendations should be integrated to manage changes in fat and lean body mass.
Bone Health BMD decreases during GnRHa treatment, particularly in AMAB individuals. Recovery during GAHT is partial, and concerns remain about long-term skeletal health. No increased osteoporosis incidence has been observed. Bone turnover markers indicate suppressed bone activity. Lack of standardized long-term follow-up studies limits understanding of adulthood skeletal outcomes. Bone health monitoring should be a priority. Clinicians should encourage lifestyle measures to support bone health, including weight-bearing exercise and vitamin D supplementation. Long-term follow-up is needed to assess osteoporosis risk.
Mental Health Significant improvements in global functioning, reduction in emotional and behavioral problems, and decrease in suicidality among adolescents receiving GnRHa, especially when followed by GAHT. Depression and anxiety levels drop significantly post-treatment, but body dissatisfaction and anxiety persist in some cases, particularly among AFAB individuals. Limited data on long-term psychiatric outcomes. Mental health support should be integrated throughout the transition process. While GnRHa shows clear benefits for suicidality and depression, continued psychological care is essential to address body image concerns and residual anxiety.

AFAB, assigned female at birth; AMAB, assigned male at birth; BMI, body mass index; MBD, bone mineral density; GAHT, gender-affirming hormone therapy; GnRHa, gonadotrophin releasing-hormone agonist; TGD, transgender and gender-diverse.