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

## TL;DR

This study explores how estrogen therapy affects bone health in a rat model of transgender individuals with high blood pressure, finding that estrogen helps protect bones despite low testosterone.

## Contribution

The study demonstrates estrogen's protective effects on bone health in a hypertensive rat model under gender-affirming hormone therapy.

## Key findings

- Estrogen treatment enhanced bone-forming cell potential in orchiectomized hypertensive rats.
- Estrogen reduced bone damage and preserved mechanical strength in the femur.
- Estrogen mitigated the negative effects of testosterone depletion on bone marrow progenitor cells.

## Abstract

Transgender people often undergo gender-affirming hormone therapy (GAHT) to address the incongruence with their gender identity. This treatment adjusts hormone levels and reduces physical traits that do not match a person’s gender identity. While GAHT is important for many transgender people, scientists are still studying how it affects the body. For example, transgender women who take estrogen may have a higher risk of heart problems. Estrogen also affects bone health, but past studies have shown mixed results. It is still unclear whether this therapy helps or harms bones over time. High blood pressure is known to cause more bone loss. So, we studied how estrogen affects bone health in a special animal model designed to reflect transgender people with high blood pressure. Our findings showed that estrogen helped protect bone health, even when testosterone levels were low due to surgery. Specifically, estrogen supported bone-forming cells and reduced damage to the femur, the large bone in the leg. These results suggest that estrogen therapy may help protect bones in certain cases, but more research is needed to understand its long-term effects fully.

The goal of gender-affirming hormone therapy (GAHT) is to align an individual’s physical characteristics with their gender identity by suppressing endogenous sex hormones and replacing them with those consistent with their gender. Transgender women undergoing GAHT are at higher risk of cardiovascular complications, and since clinical evidence suggests that hypertension is associated with increased bone loss, we investigated the effects of estrogen treatment on bone health in a hypertensive transgender animal model. Male spontaneously hypertensive rats were orchiectomized (Orch), and half of them received estrogen treatment (Orch + Es), while a third group remained 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 to those from Orch rats. Histological analysis revealed a higher number of osteocytes and fewer adipocytes in the Orch + Es group. Mechanical testing showed reduced bone strength 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 preclinical model of GAHT in hypertensive rats.