Background: Gender-affirming hormone treatment (GAHT) aligns transgender women’s hormone profiles with their gender identity, alleviating gender dysphoria by inducing feminising changes. However, the effects of GAHT on musculoskeletal health, particularly bone mineral density (BMD), require ongoing evaluation. A previous meta-analysis showed GAHT had a small effect on lumbar spine (LS) BMD, but more recent studies and updated methodologies justify a new synthesis. Methods: A systematic review and meta-analysis were conducted using studies published in English up to 31/07/2024, identified via three electronic databases, cross-referencing, and expert review. Primary outcomes were changes in femoral neck (FN), LS, and total hip (TH) BMD. Secondary outcomes included changes in body composition. Standardised effect sizes (Hedges’ g) were pooled using the inverse heterogeneity (IVhet) model. Results: GAHT was associated with a significant increase in FN BMD (g = 0.13 [0.05, 0.20], p = 0.00). Significant gains were also observed in fat mass (FM) (g = 0.52), BMI (g = 0.16), and body fat percentage (BF%) (g = 0.79), while reductions were found in fat-free mass (FFM) (g = -0.21) and thigh muscle cross-sectional area (mCSA) (g = -1.02). Conclusion: GAHT maintains FN BMD in transgender women with increased FM and reduced fat-free mass. The heterogeneous nature of several outcomes and the absence of empirical data on ageing transgender women require further research and clinical monitoring of bone health (such as High-resolution peripheral quantitative computed tomography) and muscle health to clarify the long-term implications of GAHT, particularly as transgender women age.

BRH has received financial compensation for serving as an expert witness in legal proceedings related to transgender physiology. All other authors declare no conflicts of interest.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024573102

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors

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