Background: Cross-sex hormone therapy (CHT) changes the physical characteristics of transgender women to match their gender identity and expression. This study aimed to determine the effects of feminizing cross-sex hormones on body composition, bone mineral density (BMD) and muscle strength in transgender women. Methods: A prospective observational study assessed 11 participants who underwent feminizing CHT. Dual energy X-ray absorptiometry (DXA), and handgrip strength were measured before CHT and after 6-months of CHT. Fat mass, lean body mass (LBM), and BMD were measured by DXA and handgrip strength was measured by hand-dynamometer. Results: Regional body fat in the trunk, legs, and gynoid region increased by 18%, 27.4%, and 27.2%, respectively after 6 months of CHT. Total body fat increased by 16.2%, while the fat mass ratio decreased by 7.2%. Although body fat increased, the android/gynoid fat ratio decreased; BMD in the lumbar spine significantly increased by 3.9% (P=0.0051), but changes in the femoral neck (P=0.1969) and total femur (P=0.4769) were not significant. Changes in LBM ranged from -3% (trunk) to -8% (arm region). Right-hand grip strength also significantly decreased by 7.7% (P=0.0467). Conclusions After 6 months of CHT, transgender women showed a general increase in fat mass and a decreased in overall LBM and handgrip strength. Increase in fat mass percentage were more remarkable in gynoid region, leading to a more “female” body fat distribution.

The activation of neurotrophic signaling pathways following the upregulation of glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β family, has a potential neuroprotective effect in the adult brain. Herein, we report that hippocampal transduction of adeno-associated virus serotype 1 (AAV1) with a constitutively active form of ras homolog enriched in brain [Rheb(S16H)], which can stimulate the production of brain-derived neurotrophic factor (BDNF) in hippocampal neurons, induces the increases in expression of GDNF and GDNF family receptor α-1 (GFRα-1), in neurons and astrocytes in the hippocampus of rat brain in vivo . Moreover, upregulation of GDNF and GFRα-1 contributes to neuroprotection against thrombin-induced neurotoxicity in the hippocampus. These results suggest that AAV1-Rheb(S16H) transduction of hippocampal neurons, resulting in neurotrophic interactions between neurons and astrocytes, may be useful for neuroprotection in the adult hippocampus.