Feminising hormone therapy reduces testicular ACE-2 receptor expression: Implications for treatment or prevention of COVID-19 infection in men.

Abstract

It has been proposed that men hospitalised with COVID‐19 be treated with oestrogen or progesterone to improve COVID‐19 outcomes. Transgender women (male‐to‐female) are routinely treated with oestrogen or oestrogen +progesterone for feminisation which provides a model for the effect of feminising hormones on testicular tissue. Our goal was to analyse differences in ACE‐2 expression in testicles of trans‐women taking oestrogen or oestrogen +progesterone. Orchiectomy specimens were collected from trans‐women undergoing gender‐affirming surgery, who were taking oestrogen or oestrogen+progesterone preoperatively. For controls, we used benign orchiectomy specimens from cis‐gender men. All specimens were stained with H&E, Trichrome (fibrosis), insulin‐like 3 antibody (Leydig cell) and ACE‐2 IHC. Cells per high‐powered field were counted by cell type (Leydig, Sertoli and Germ). Stain intensity was rated on a 0–2 scale. On immunohistochemistry staining for Leydig cells and ACE‐2 staining, the oestrogen+progesterone cohort had fewer Leydig cells compared with controls. The oestrogen+progesterone cohort also had greater degree of tissue fibrosis compared with controls and the oestrogen cohort. This work supports the hopeful possibility that a short course of progesterone (or oestrogen+progesterone) could downregulate ACE‐2 to protect men from COVID‐19 infection.