The use of gonadotropin-releasing hormone agonists has a negative effect on bone mass in transgender youth, according to data from 172 individuals.
The onset of puberty and pubertal hormones contributes to the development of bone mass and body composition in adolescence, wrote Behdad Navabi, MD, and colleagues at Children’s Hospital of Eastern Ontario, Canada. Although the safety and efficacy of gonadotropin-releasing hormone agonists (GnRHa) has been described in short-term studies of youth with gender dysphoria, concerns persist about suppression of bone mass accrual from extended use of GnRHas in this population, they noted.
In a study published in Pediatrics, the researchers reviewed data from 172 youth younger than 18 years of age who were treated with GNRHa and underwent at least one baseline dual-energy radiograph absorptiometry (DXA) measurement between January 2006 and April 2017 at a single center. The standard treatment protocol started with three doses of 7.5 mg leuprolide acetate, given intramuscularly every 4 weeks, followed by 11.25 mg intramuscularly every 12 weeks after puberty suppression was confirmed both clinically and biochemically. Areal bone mineral density (aBMD) measurement z scores were based on birth-assigned sex, age, and ethnicity, and assessed at baseline and every 12 months. In addition, volumetric bone mineral density was calculated as bone mineral apparent density (BMAD) at the lower spine, and the z score based on age-matched, birth-assigned gender BMAD.
Overall, 55.2% of the youth were vitamin D deficient or insufficient at baseline, but 87.3% were sufficient by the time of a third follow-up visit after treatment with 1,000-2,000 IU of vitamin D daily; no cases of vitamin D toxicity were reported.
At baseline, transgender females had lower z scores for the LS aBMD and BMAD compared to transgender males, reflecting a difference seen in previous studies of transgender youth and adult females, the researchers noted.
The researchers analyzed pre- and posttreatment DXA data in a subgroup of 36 transgender females and 80 transgender males to identify any changes associated with GnRHa. The average time between the DXA scans was 407 days. In this population, aBMD z scores at the lower lumbar spine (LS), left total hip (LTH), and total body less head (TBLH) decreased significantly from baseline in transgender males and females.
Among transgender males, LS bone mineral apparent density (BMAD) z scores also decreased significantly from baseline, but no such change occurred among transgender females. The most significant decrease in z scores occurred in the LS aBMD and BMAD of transgender males, with changes that reflect findings from previous studies and may be explained by decreased estrogen, the researchers wrote.
In terms of body composition, no significant changes occurred in body mass index z score from baseline to follow-up in transgender males or females, the researchers noted, and changes in both gynoid and android fat percentages were consistent with the individuals’ affirmed genders. No vertebral fractures were detected.
However, GnRHa was significantly associated with a decrease in total body fat percentage and a decrease in lean body mass (LBM) in transgender females.
The study findings were limited by several factors, including the lack of consistent baseline physical activity records, and limited analysis at follow-up of the possible role of physical activity in bone health and body composition, the researchers noted. However, the results were strengthened by the relatively large study population with baseline assessments, and by the pre- and posttreatment analysis, they added.
“Evidence on GnRHa-associated changes in body composition and BMD will help health care professionals involved in the care of youth with GD [gender dysphoria] to counsel appropriately and optimize their bone health,” the researchers said. “Given the absence of vertebral fractures detected in those with significant decreases in their LS z scores, the significance of BMD effects of GnRHa in transgender youth needs further study, as well as whether future spine radiographs are needed on the basis of BMD trajectory,” they concluded.