A Preclinical Investigation of Estrogenic Bone Protection in a Hypertensive Rat Model Under Gender-Affirming Hormone Therapy

Abstract

Abstract: The goal of gender-affirming hormone therapy (GAHT) is to align an individual’s physical characteristics with their gender identity by suppressing endogenous sexhormones and replacing them with those consistent with their gender. Transgenderwomen undergoing GAHT are at higher risk of cardiovascular complications, and sinceclinical evidence suggests that hypertension is associated with increased bone loss, weinvestigated the effects of estrogen treatment on bone health in a hypertensivetransgender animal model. Male spontaneously hypertensive rats were orchiectomized(Orch), and half of them received estrogen treatment (Orch + Es), while a third groupremained intact as controls. Bone marrow progenitor cells (BMPCs) were isolated to assess osteogenic potential, and femurs were collected for histological and mechanical analysis. BMPCs from Orch + Es rats exhibited enhanced osteogenic potential compared tothose from Orch rats. Histological analysis revealed a higher number of osteocytes andfewer adipocytes in the Orch + Es group. Mechanical testing showed reduced bonestrength in Orch rats, which was partially preserved in Orch + Es animals. In conclusion,estrogen administration mitigated the deleterious effects of testosterone depletion on BMPCs and provided protective effects on bone structure and strength in this preclinicalmodel of GAHT in hypertensive rats.