Balance bone health concerns with potential benefits
The effect of estrogen and testosterone on bone geometry in puberty varies, and the increase in the use of GnRHa as part of a multidisciplinary gender transition plan makes research on the skeletal impact of this therapy in transgender youth a top priority, Laura K. Bachrach, MD, of Stanford (Calif.) University, and Catherine M. Gordon of Harvard Medical School, Boston, wrote in an accompanying editorial.
The decrease in areal bone mineral density and in bone mineral apparent density (BMAD) z scores in the current study is not unexpected, but the key question is how much bone density recovers once the suppression therapy ends and transgender sex steroid use begins, they said. “Follow-up studies of young adults treated with GnRHa for precocious puberty in childhood are reassuring,” they wrote. “It is premature, however, to extrapolate from these findings to transgender youth,” because the impact of gender-affirming sex steroid therapy on the skeleton at older ages and stages of maturity are unclear, they emphasized.
In the absence of definitive answers, the editorial authors advised clinicians treating youth with gender dysphoria to provide a balanced view of the risks and benefits of hormone therapy, and encourage adequate intake of dietary vitamin D and calcium, along with weight-bearing physical activity, to promote general bone health. “Transgender teenagers and their parents should be reassured that some recovery from decreases in aBMD during pubertal suppression with GnRHa is likely,” the authors noted. Bone health should be monitored throughout all stages of treatment in transgender youth, but concerns about transient bone loss should not discourage gender transition therapy, they emphasized. “In this patient group, providing a pause in pubertal development offers a life-changing and, for some, a life-saving intervention,” they concluded.
Comparison to cisgender controls would add value
“This study is important because one of the major side effects of GnRH agonists is decreased bone density, especially the longer that patients are on them,” M. Brett Cooper, MD, of UT Southwestern Medical Center, said in an interview. The findings add to existing data to underscore the importance of screening for low bone density and low vitamin D levels, Dr. Cooper added.
Dr. M. Brett Cooper
Dr. Cooper said that he was not surprised by the study findings. “I think that this study supported what clinicians already knew, which is that GnRH agonists do potentially cause a decline in bone mineral density and thus, you need to support these patients as best you can with calcium, vitamin D, and weight-bearing exercise,” he noted.
Dr. Cooper emphasized two main take-home points from the study. “First, clinicians who prescribe GnRH agonists need to ensure that they are checking bone density and vitamin D measurements, and then optimizing these appropriately,” he said. “Second, when a bone density is found to be low or a vitamin level is low, clinicians need to ensure that they are monitored and treated appropriately.” Clinicians need to use these data when deciding when to start gender-affirming hormones so their patients have the best chance to recover bone density, he added.
“I think one confounding factor on this study is the ranges they used for vitamin D deficiency,” Dr. Cooper noted. “This study was done in Canada, and the scale used was in nmol/L, while most labs in the U.S. use ng/mL,” he said. “Most pediatric and adolescent societies in the United States use < 20 ng/mL as an indicator of vitamin D deficient and between 20 and 29 ng/mL as insufficient,” he explained, citing the position statement on recommended vitamin D intake for adolescents published by The Society for Adolescent Health and Medicine. In this study, the results converted to < 12 ng/mL as deficient and between 12 and 20 ng/mL as insufficient, respectively, on the U.S. scale, said Dr. Cooper.
“Therefore, I can see that there are cases where someone may have been labeled vitamin D insufficient in this study using their range, whereas in the U.S. these patients would be labeled as vitamin D deficient and treated with higher-dose supplementation,” he said. In addition, individuals with levels between 20 ng/mL and 29 ng/mL in the U.S. would still be treated with vitamin D supplementation, “whereas in their study those individuals would have been labeled as normal,” he noted.
As for future research, it would be useful to study whether bone mass in transgender young people differs from age- and gender-matched controls who are not gender diverse (cisgender), Dr. Cooper added. “It may be possible that the youth in this study are not different from their peers and maybe the GnRH agonist is not the culprit,” he said.
The study received no outside funding. The researchers, editorial authors, and Dr. Cooper had no financial conflicts to disclose.