Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty

Abstract

Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender‐affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people, no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin‐releasing hormone agonist (GnRHa) and GAH before achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip structure analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual‐energy X‐ray absorptiometry scans performed at the start of GnRHa and GAH treatments, and after ≥2 years of GAH treatment. Mixed‐model analyses were performed to study differences over time. Data were visually compared with reference values of the general population. A total of 322 participants were included, of whom 106 were trans women and 216 trans men. In both trans women and trans men, participants resembled the reference curve for SPW and ED of the experienced gender but only when GnRHa was started during early puberty. Those who started during mid and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one's life span. Therefore, this study adds insights into sex‐specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population. © 2021 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

A systematic review of hormone treatment for children with gender dysphoria and recommendations for research

“…One study investigated bone geometry. 20 Six studies were retrospective [21][22][23][24][25][26] and one study was prospective. 20 An additional study was cross-sectional where study participants in early puberty (Tanner stages 2-3) were examined only once, before the start of GnRHa therapy.…”

Gender‐affirming hormone therapy: An updated literature review with an eye on the future

“…The effect on periosteal and endocortical growth in bone geometry is partly regulated by sex steroids. As GAHT changes the hormonal exposure, it plays a key role in bone turnover and preserving bone mineral density (BMD) [69, 70].…”

“…After ≥2 years of GAHT, they found a similar subperiosteal width and endocortical diameter to the experienced gender when GnRHa was started during early puberty. Trans participants starting in mid‐ and late puberty remained within the reference curve of the sex assigned at birth [69].…”

“…A retrospective cohort study from van der Loos et al. [69] investigated the changes in bone geometry among trans adolescents (106 trans girls and 216 trans boys) using GnRHa and GAHT when started in different stages of puberty. After ≥2 years of GAHT, they found a similar subperiosteal width and endocortical diameter to the experienced gender when GnRHa was started during early puberty.…”

Interpretation of Bone Mineral Density Z-Scores by Dual-Energy X-Ray Absorptiometry in Transgender and Gender Diverse Youth Prior to Gender-Affirming Medical Therapy

“…Data regarding hip bone geometry indicate that TGD adults who initiated pubertal suppression in early puberty resemble the reference curves of the affirmed gender, but those who initiated gender-affirming medical therapy in middle to late puberty more closely followed the hip geometry reference curves of the sex designated at birth ( 15 ). Over time, if these early pubertal TGD youth go on to initiate gender-affirming hormone therapy with estradiol or testosterone, it would especially make sense to compare BMD Z-scores using the reference standards of the affirmed gender rather than by the sex designated at birth; in fact, this would be congruent with the recommendations included in the 2019 ISCD Adult Position Statement ( 8 , 9 ).…”