Testosterone Deficiency, Long-Term Testosterone Therapy, and Cardiovascular Risk: A Longitudinal Study
Abstract
Cardiovascular disease is the major cause of morbidity and the leading cause of death globally. As compared to women, men have a higher cardiovascular risk. Recent studies suggest that testosterone as it is the most abundant male hormone plays a critical role in limiting vascular inflammation and maintaining normal lipid and glucose metabolism, and testosterone deficiency in aging men may contribute to the elevated cardiovascular risk in the male gender. Studies investigated the effect of low baseline testosterone level or testosterone measured at one single point in time on cardiovascular risk. However, the association between time-varying testosterone levels or recent testosterone changes (e.g., sudden drop-offs) and cardiovascular events have not yet been studied. Moreover, whether these associations differ between patients with prior cardiovascular events and those without is unknown. Additionally, whether testosterone deficiency is associated with major cardiovascular disease pathways such as inflammation biomarkers is not clear; how long-term testosterone therapy, a treatment to improve testosterone levels, influences cardiovascular disease development, and its longitudinal effect on inflammation, have not been elucidated.
In this study, we used data of776 hypogonadal men from a registry study in Germany and the National Health and Nutrition Examination Survey (NHANES) data and applied Cox proportional hazards regression models, linear mixed effect models, linear and logistic regression models to investigate the association of time-varying testosterone level and testosterone changes since the last visit and cardiovascular events, stratified by prior cardiovascular event status; the association between testosterone deficiency and inflammation biomarkers (C-reaction protein (C-RP), alanine aminotransferase (ALT), aspartate aminotransferase (AST)); the effect of long- term testosterone therapy on the risk of cardiovascular events and inflammation biomarkers. We found lower time-varying testosterone level and greater testosterone declines since the last visit were associated with a higher risk of myocardial infarction, and the associations were not different among patients with prior cardiovascular events and those without. Testosterone deficiency was associated with higher levels of C-RP and ALT; long-term testosterone therapy alleviated inflammation and reduced cardiovascular events. Clinicians should be informed of the effect of testosterone on cardiovascular health when assessing male patients' cardiovascular risk and make sure timely treatment is prescribed if needed.
Citation
Zhang, Xiao (2020). Testosterone Deficiency, Long-Term Testosterone Therapy, and Cardiovascular Risk: A Longitudinal Study. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /192351.