Sex Steroid Metabolite Profile and Gonadotrophins during Hormone Therapy in Transgender Adolescents

Norup Pernille Badsberg; Haahr Mette Ewers; Mohsin Aslam; Annamaria Giraldi; Pagsberg Anne Katrine; Peter Christiansen; Lise Aksglaede; Line Cleemann; Hanne Frederiksen; Trine Johannsen; Anders Juul; Katharina Main

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ESPE Abstracts (2024) 98 P1-192

ESPE2024 Poster Category 1 Sex Endocrinology and Gonads 2 (8 abstracts)

Sex Steroid Metabolite Profile and Gonadotrophins during Hormone Therapy in Transgender Adolescents

Pernille Badsberg Norup ^1,2 , Mette Ewers Haahr ^3,4 , Mohsin Aslam ^1,2 , Annamaria Giraldi ^3,4 , Anne Katrine Pagsberg ^3,5 , Peter Christiansen ^1,2 , Lise Aksglaede ^1,2 , Line Cleemann ^1,2 , Hanne Frederiksen ^1,2 , Trine Johannsen ^1,2 , Anders Juul ^1,2,3 & Katharina Main ^1,2,3

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¹Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. ²International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. ³Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. ⁴Sexological Clinic, Mental Health Centre, Copenhagen, Copenhagen University Hospital – Mental Health Services CPH, Copenhagen, Denmark. ⁵Child and Adolescent Mental Health Center, Copenhagen University Hospital – Mental Health Services CPH, Copenhagen, Denmark

Background & Aim: The national Danish assessment and hormone treatment program for transgender adolescents started in 2016 and follows international guidelines. We aim to investigate the effects of hormone therapy on the sex steroid metabolite profile and gonadotropins.

Methods: This observational study includes 219 transgender adolescents who started hormone therapy before 18 years of age comprising 55 individuals assigned male at birth (trans girls) and 164 individuals assigned female at birth (trans boys). Hormone therapy consists of gonadotropin-releasing hormone analogs (GnRHa) and sex steroids, i.e., β-estradiol or testosterone. Blood samples and clinical parameters were collected at routine visits. The laboratory analyses were performed at DANAK-certified laboratories. Mixed-model analyses were used for statistical analyses after 6, 12, and 24 months.

Results: During GnRHa monotherapy, LH, FSH, testosterone, estradiol, and estrone were suppressed in both groups. SHBG decreased in trans boys at all time points (-10.8 nmol/L after 24 months, P <0.01) but not in trans girls. Inhibin B decreased in both groups (-38.0 ng/L, P <0.001 in trans boys, and -66.1 ng/L, P <0.001 in trans girls, after 24 months). After 12 months, we observed an increase in AMH in both groups, which was most pronounced in the trans girls (+287.3 pmol/L after 24 months, P <0.01). Testosterone, estradiol, and estrone increased when testosterone treatment was added in trans boys (+17.3 nmol/L, +77.3 pmol/L, and +89.4 pmol/L after 24 months, P <0.001) and SHBG decreased further (-21.7 nmol/L after 24 months, P <0.001). FSH and LH increased after 24 months (+1.7 and +2.0 IU/L, P <0.001) after stopping GnRHa. No changes in AMH were observed. In trans girls, LH and FSH decreased further when estradiol was added. Estradiol and estrone levels increased (+246.2 pmol/L and +2320.3 pmol/L after 24 months, P <0.001). There were no changes in AMH, an increase in SHBG (+43.3 nmol/L after 24 months, P <0.001), and a further decrease in inhibin B (-66.0 ng/L after 12 months, P <0.001).

Conclusion: GnRHa monotherapy suppressed as expected the hypothalamic-pituitary-gonadal axis which also included AMH which may reflect changes in follicle recruitment and Sertoli cell function. The increasing levels of FSH and LH levels in trans boys on testosterone monotherapy may explain breakthrough bleeding in some. The increased SHBG during estradiol treatment is in line with increased SHBG in cis girls receiving the contraceptive pills.