SAT644 Gender Affirming Hormone Therapy (GHAT) In Adult Male-to-female Mice Increases Cortical And Trabecular Bone, Resulting In An Increase In Bone Strength

Disclosure: J.D. Zajac: None. T. Nie: None. V. Venkatesh: None. S. Golub: None. K. Stok: None. R. Desai: None. D.J. Handelsman: None. R.A. Davey: None. There are conflicting reports of the effects of GAHT on bone health and fracture risk in adult transgender women, and the underlying changes are poorly understood. We aimed to determine the effects of GAHT administered during adulthood on bone microarchitecture and strength in a mouse model of male-to-female transition. To model male-to-female transition in adults, C57BL/6 male mice aged 16 weeks that had reached peak bone mass were administered an estradiol-filled silastic implant (∼1.3mg) intraperitoneally for 12 weeks. Controls included vehicle treated intact males and females, n=9-10/group. At study end, serum sex steroids were determined by LCMS/MS, femoral bone microarchitecture by μ-CT, and strength by 3-point bending. Mean serum estradiol was 4.7-fold higher in males treated with estradiol (91.8±10.4 pg/mL) than the peak estradiol levels observed during the proestrus stage of the estrus cycle in adult female mice (19.4±13.5 pg/mL, Handelsman, 2020). Estradiol treatment in males increased the endocortical deposition of bone evidenced by an increase in cortical thickness (mm)(P<0.05) and a decrease in medullary volume (mm(3))(P<0.05) compared to male and female controls. Periosteal circumference was not effected by estradiol treatment in males compared to controls. Trabecular bone volume/tissue volume (%) was 4-fold higher in estradiol treated males compared to male controls and 12-fold higher than female controls due to an increase in trabecular number (μm)(P<0.0001). The increase in both cortical and trabecular bone contributed to increased bone strength, as the maximum force (N) the bone could withstand prior to fracture was 2-fold higher in males treated with estradiol compared to both male and female controls (P<0.0001). Measurement of the material properties of the femur showed an increase in ultimate stress (MPa)(P<0.001) and elastic modulus (MPa)(P<0.01) in males following estradiol treatment compared to male controls, indicative of increased rigidity. In this model of adult male-to-female transition, supraphysiological levels of estradiol in male mice increases cortical and trabecular bone mass leading to increased bone strength. The increased rigidity of the femur following estradiol treatment suggests increased bone mineral content. It may be possible therefore, to preserve bone health and prevent fractures in trans women treated with GAHT, however a dose of estradiol that protects the bone without adverse side effects needs to be identified. Presentation: Saturday, June 17, 2023