J Bone Miner Res. 2021 May;36(5):931941. doi: 10.1002/jbmr.4262. PMID: 33507568.
This restrospective study of the Cohort of Gender Dysphoria investigated bone geometry parameters of 106 adolescent trans-women and 216 adolescent trans-men during early and late start of gonadotropin-releasing hormone agonist (GnRHa) and gender affirming hormone therapy (GAHT). Transgender youth who started treatment early in puberty developed bone geometry according to their experienced gender, while a later start resulted in bone geometry resembling their gender assigned at birth.
So far, most studies on bone health of transgender youth receiving hormonal treatments focused on bone density and biochemical bone turnover markers, and found differential effects depending on treatments (GnRHa only, GnRHa plus GAHT) and start of intervention (early versus late in puberty; e.g. (1)). Here, van der Loos et al. show nicely that, with earlier diagnosis and treatment of transgender individuals, treatments will modulate the human body differently, given the fact that they will interfere with pubertal development. This is certainly not only true for bone development, but also for all other sex steroid regulated developmental changes seen with puberty, including growth, body composition and neurodevelopment.
Overall, it can be assumed that the typical programming of pubertal development can be best trans-modulated in the direction of experienced gender when endogenous hormones are halted early, and cross-hormone treatment started early (by Tanner stage 2). However, as we learn step by step from interdisciplinary gender medicine studies in recent years, gender medicine is more complex and is not only modulated by sex steroids. It is known that underlying sex-related genes regulate a vast range of body functions by other means that we have not yet on our focus when it comes to trangender medicine. Long-term follow up of hormonally treated transgender individuals is therefore mandatory to learn more about possible late effects and adapt current treatments.
Reference: 1. Schagen SEE, Wouters FM, Cohen-Kettenis PT, Gooren LJ, Hannema SE. Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e425263.