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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.

SUBMITTER: Masterson JM

PROVIDER: S-EPMC8646357 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionHIV infections and the use of amphetamine-type stimulants (ATS) among men who have sex with men (MSM) have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM.MethodsWe conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 25 April 2013. Pooled estimates of the association--prevalence rate ratios (PRR, cross-sectional studies), odds ratio (OR, case-control studies) and hazard ratio (HR, longitudinal studies), with 95% Confidence Intervals (CI)--were calculated using random-effects models stratified by study design and ATS group (meth/amphetamines vs. ecstasy). We assessed the existence of publication bias in funnel plots and checked for sources of heterogeneity using meta-regression and subgroup analysis.ResultsWe identified 6710 article titles, screened 1716 abstracts and reviewed 267 full text articles. A total of 35 publications were eligible for data abstraction and meta-analysis, resulting in 56 records of ATS use. Most studies (31/35) were conducted in high-income countries. Published studies used different research designs, samples and measures of ATS use. The pooled association between meth/amphetamine use and HIV infection was statistically significant in all three designs (PRR = 1.86; 95% CI: 1.57-2.17; OR = 2.73; 95% CI: 2.16-3.46 and HR = 3.43; 95% CI: 2.98-3.95, respectively, for cross-sectional, case-control and longitudinal studies). Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR = 1.15; 95% CI: 0.88-1.49; OR = 3.04; 95% CI: 1.29-7.18 and HR = 2.48; 95% CI: 1.42-4.35, respectively, for cross-sectional, case-control and longitudinal studies). RESULTS in cross-sectional studies were highly heterogeneous due to issues with ATS measurement and different sampling frames.ConclusionsWhile meth/amphetamine use was significantly associated with HIV infection among MSM in high-income countries in all study designs, evidence of the role of ecstasy in HIV infection was lacking in cross-sectional studies. Cross-sectional study design, measurement approaches and source populations may also be important modifiers of the strength and the direction of associations. Event-specific measure of individual drug is required to establish temporal relationship between ATS use and HIV infection. HIV prevention programmes targeting MSM should consider including interventions designed to address meth/amphetamine use.

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

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