Testosterone Level Reduction Increases the 10-Year Risk of Cardiovascular Diseases: A Retrospective Cohort Study in a Taiwanese Young Male Population

Abstract

Low testosterone levels are associated with increased risk of cardiovascular disease; however, most previous studies assessed the relationship of testosterone levels with a history of cardiovascular (CV) events rather than with CV risk prediction scores consequently neglecting the effect of testosterone on CV risk in healthy young individuals. The aim of this study was to investigate the relationship between testosterone levels and predict the 10-year risk of cardiovascular disease. This retrospective cohort study was conducted through a large medical health examination system in four metropolises in Taiwan. Two risk scores were used to predict the 10-year cardiovascular risk of participants: the Framingham Risk Score (FRS) (2008) and the Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator (2013). Multivariate-adjusted logistic regression was used to calculate odds ratios (ORs) for the correlation of testosterone level reduction with the increase in predicted CV risk. We used the MJ Health Research Foundation database to collect reports of 125,414 individuals who underwent medical checkups between 2007 and 2016. The final sample size included 1,253 male participants. A reduction in testosterone level between two subsequent medical checkups was associated with higher CV risk estimated by the FRS and ASCVD Risk Estimator in young participants aged 30–49 years (OR = 0.804, 95% CI: 0.711–0.909, p < 0.01 and OR = 0.841, 95% CI: 0.742–0.953, p < 0.01, respectively). Reduction in total testosterone levels increases CV risk in men aged 30 to 49 years, while the CV risk is not influenced by low testosterone levels at baseline.

Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment

“…5,23,[27][28][29]32,94,107,[134][135][136][137][138][139] Lower testosterone also associates with other pathologies that present greater risk of COVD-19 severity including cardiovascular disease, diabetes, and obesity in men, which may contribute to the overall severity in male COVID-19 patients. [140][141][142][143][144][145][146] Both ACE2 and TMPRSS2 are expressed in Leydig cells of the testes, the principal site for androgen synthesis, and SARS-CoV-2 infection could potentially impair the synthetic capacity to produce testosterone. 147,148 The testes also contains a local RAS specifically within Leydig cells including expression of both canonical and alternative arms of the RAS.…”

“…140–146 Both ACE2 and TMPRSS2 are expressed in Leydig cells of the testes, the principal site for androgen synthesis, and SARS-CoV-2 infection could potentially impair the synthetic capacity to produce testosterone. 147,148 The testes also contains a local RAS specifically within Leydig cells including expression of both canonical and alternative arms of the RAS. 149 Ang II via stimulation of the AT 1 R attenuated both basal and LH (luteinizing hormone)-stimulated testosterone release in isolated Leydig cells from rat, while the functional actions of Ang-(1–7) in the testes are currently unknown.…”