Are Low Testosterone Levels Linked to Atherosclerosis in Men?
Comments by Erin D. Michos, MD, Associate Professor of Medicine and Epidemiology and Associate Director of Preventive Cardiology at Johns Hopkins University School of Medicine
Low testosterone levels in men were associated with an increased risk for vascular calcification in an age-adjusted analysis of data from the Framingham Heart Study, but not in an analysis that adjusted for conventional risk factors for coronary heart disease, such as body mass index and diabetes. The findings were published in the May issue of The Journal of Clinical Endocrinology and Metabolism.
“The link between sex hormone levels with calcification of the arteries (a marker of atherosclerosis) has been somewhat controversial with studies showing both positive and negative associations,” commented Erin D. Michos, MD, who also has conducted research in this field. Dr. Michos is Associate Professor of Medicine and Epidemiology and Associate Director of Preventive Cardiology at Johns Hopkins University School of Medicine in Baltimore, MD.
“In this study, having low testosterone was associated with greater risk for vascular calcification when you don’t consider traditional risk factors such as blood pressure, cholesterol, body mass index, diabetes. However, once these traditional risk factors were accounted for, the association was no longer significant.”
Findings Based on Framingham Heart Study Data
The cross-sectional observational study included 1,654 men (mean age, 49 years) enrolled in the Offspring and the Third-Generation cohort of the Framingham Heart Study. Coronary, abdominal, and thoracic aortic calcification was measured using multidetector computed tomography.
In an age-adjusted analysis, vascular calcification at all sites was negatively associated with total testosterone and calculated free testosterone, but was positively associated with estradiol and estrone levels (Table). For example, each 100-ng/dL between-subjects increase in total testosterone was associated with a mean difference in risk of coronary artery calcification of -23% (P=0.02). However, these associations between testosterone and vascular calcification were no longer statistically significant after adjusting for other cardiovascular risk factors (Table).
Based on the findings, Dr. Michos did not see clinical value in incorporating sex hormones levels into cardiovascular risk prediction. “There was still an association seen with lower estradiol and more coronary artery calcification in men, but the relationship was very modest,” she noted.
“Most importantly, low testosterone might simply be a good surrogate marker of a poorer health state and not linked to atherosclerosis in a causal fashion,” Dr. Michos said. “This study was cross-sectional, which makes it difficult to determine the direction of the association. It could go the other way to suggest that men with subclinical cardiovascular disease might be more likely to have poorer health, elevated body mass index, and poorer lifestyle conditions that then leads to lower testosterone levels,” Dr. Michos said.
Relationship May Be Different in Women
“In a prior paper that my group published in Atherosclerosis in 2008, we also found that after adjusting for traditional cardiovascular risk factors, there was no association of sex hormones in men with vascular calcification in the abdominal aorta,” Dr. Michos said. In contrast, the relationship was different in women.
“Women with higher sex hormone binding globulin (SHBG) levels were less likely to have abdominal aortic calcification (OR=0.62 for 1 unit greater log[SHBG] level) after adjusting for non-lipid cardiovascular risk factors, Dr. Michos explained.
June 23, 2016