Summary

This review was one of the evidence reviews behind the Endocrine Society's 2017 guideline on treating gender dysphoria (distress about one's sex). The Mayo Clinic team combined 13 studies (639 people, mostly adults) that measured bone density before and after cross-sex hormones. Testosterone in females made no measurable difference to spine or hip bone density over one to two years. Estrogen in males slightly raised spine bone density. Only one study looked at broken bones (none in a year), and only one looked at teenagers given puberty blockers (drugs that pause puberty) and then hormones. That study found males had lower spine bone density at age 22 than before treatment. The authors said the effect on the risk of broken bones is uncertain. The review is reassuring about short-term bone density in adults, but cannot show long-term safety, fracture risk, or safety for teenagers.

Key findings

• De review combineerde 13 studies over 639 mensen: 392 als man geboren en 247 als vrouw geboren.
• Bij vrouwen op testosteron veranderde de botdichtheid in onderrug en heup na een of twee jaar niet meetbaar.
• Bij mannen op oestrogeen steeg de botdichtheid in de onderrug licht na een jaar en iets meer na twee jaar.
• Slechts één studie, onder 53 mannen en 53 vrouwen, keek naar botbreuken en vond er in 12 maanden geen.
• Slechts één studie omvatte tieners die puberteitsblokkers en daarna hormonen kregen, en die vond dat mannen op 22-jarige leeftijd een lagere botdichtheid in de wervelkolom hadden dan vóór de behandeling.
• De auteurs zeiden dat het meeste bewijs kwam van studies met een matig risico op misleiding, en dat het effect op het risico op botbreuken onzeker is.
• De review werd uitgevoerd voor de Endocrine Society, met een plan gemaakt met haar experts, ter ondersteuning van haar richtlijn uit 2017.

Abstract

BACKGROUND: The impact of sex steroids on bone health in transgender individuals is unclear.

METHODS: A comprehensive search of several databases to 7 April 2015 was conducted for studies evaluating bone health in transgender individuals receiving sex steroids. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CIs).

RESULTS: Thirteen studies evaluating 639 transgender individuals were identified [392 male-to-female (MTF), 247 female-to-male (FTM)]. In FTM individuals and compared with baseline values before initiation of masculinizing hormone therapy, there was no statistically significant difference in the lumbar spine, femoral neck, or total hip bone mineral density (BMD) when assessed at 12 and 24 months. In MTF individuals and compared with baseline values before initiation of feminizing hormone therapy, there was a statistically significant increase in lumbar spine BMD at 12 months (0.04 g/cm2; 95% CI, 0.03 to 0.06 g/cm2) and 24 months (0.06 g/cm2; 95% CI, 0.04 to 0.08 g/cm2). Fracture rates were evaluated in a single cohort of 53 MTF and 53 FTM individuals, with no events at 12 months. The body of evidence is derived mostly from observational studies at moderate risk of bias.

CONCLUSION: In FTM individuals, masculinizing hormone therapy was not associated with significant changes in BMD, whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient-important outcomes such as fracture risk is uncertain.

Conclusion

In FTM individuals, masculinizing hormone therapy was not associated with significant changes in BMD, whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient-important outcomes such as fracture risk is uncertain.