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

• جمعت المراجعة 13 دراسة تغطي 639 شخصاً: 392 وُلدوا ذكوراً و247 إناثاً.
• لدى الإناث اللواتي يتناولن التستوستيرون، لم تتغير كثافة العظام في أسفل العمود الفقري والورك بشكل قابل للقياس بعد سنة أو سنتين.
• لدى الذكور الذين يتناولون الإستروجين، ارتفعت كثافة عظام أسفل العمود الفقري قليلاً بعد سنة وقليلاً أكثر بعد سنتين.
• نظرت دراسة واحدة فقط، على 53 ذكراً و53 أنثى، في الكسور، ولم تجد أياً منها في 12 شهراً.
• غطت دراسة واحدة فقط مراهقين أُعطوا حاصرات البلوغ ثم الهرمونات، ووجدت أن الذكور كانت لديهم كثافة عظام عمود فقري أقل في سن 22 مما قبل العلاج.
• قال المؤلفون إن معظم الأدلة جاءت من دراسات ذات خطر متوسط للتضليل، وإن الأثر في خطر الكسور غير مؤكد.
• أُجريت المراجعة للجمعية الأمريكية للغدد الصماء، بخطة وُضعت مع خبرائها، لدعم إرشادها لعام 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.