Endocrine Abstracts

JOINT2845

Context: Transgender male adolescents undergoing gender-affirming hormone therapy (GAHT) often start with a combination of gonadotropin-releasing hormone analog (GnRHa) to suppress puberty and testosterone therapy to induce masculinizing changes. While GnRHa effectively suppresses the hypothalamic-pituitary-gonadal (HPG) axis, the degree of gonadotropin suppression achieved with testosterone monotherapy following GnRHa discontinuation remains unclear. Understanding the dynamics of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels during this transition is essential for optimizing treatment protocols and achieving desired clinical outcomes.

Aim: To investigate the degree of suppression of the HPG axis achieved by testosterone monotherapy in transgender male adolescents, as reflected by changes in LH and FSH levels following GnRHa discontinuation.

Methods: We conducted a retrospective cohort study from 2018 to 2023 at the Israeli Children and Adolescents Gender Clinic, Dana-Dwek Children’s Hospital. The cohort consisted of 68 transgender male adolescents who started GAHT at Tanner stage 4–5. Outcome measures included changes in serum LH and FSH levels, as well as the LH/FSH ratio, assessed at baseline, during combined GnRHa and testosterone therapy, and during testosterone monotherapy.

Results: Baseline LH levels were within the normal range, followed by a significant decrease during combined GnRHa and testosterone treatment, and an increase during testosterone monotherapy (6.11 ± 5.06 vs. 0.32 ± 0.50 vs. 3.17 ± 2.97 IU/l, respectively; P < 0.001). Similarly, baseline FSH levels were within the normal range, followed by a marked decrease during combined GnRHa and testosterone treatment, and an increase during testosterone monotherapy (5.87 ± 2.77 vs. 1.46 ± 1.23 vs. 4.68 ± 3.14 IU/l, respectively; P < 0.001). Post hoc analysis revealed significant differences in LH, FSH, and LH/FSH ratios across the three treatment phases.

Conclusion: In transgender male adolescents, testosterone monotherapy following GnRHa discontinuation did not lead to full HPG axis suppression, with LH and FSH levels remaining within the normal range. These findings suggest that gender-affirming testosterone alone may not completely suppress gonadotropin secretion in transgender males. Future research is needed to explore the testosterone-mediated feedback mechanisms underlying incomplete LH and FSH suppression, which could have implications for optimizing hormone therapy in transgender male adolescents.