“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).
“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
Travison TG, O’Donnell CJ, Bhasin S, et al. Circulating sex steroids and vascular calcification in community-dwelling men: The Framingham Heart Study. J Clin Endocrinol Metab. 2016;101(5):2160-2167.
Michos ED, Vaidya D, Gapstur SM, et al. Sex hormones, sex hormone binding globulin, and abdominal aortic calcification in women and men in the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis. 2008;200(2):432-438.