Endogenous sex hormone levels associated with CVD in postmenopausal women
Researchers used data from women participating in the Multi-Ethnic Study of Atherosclerosis (MESA) who did not have cardiovascular disease and had levels of testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin measured at baseline.
Higher testosterone/estradiol ratio and testosterone levels were associated with increased risk for cardiovascular disease (CVD) in postmenopausal women, a recent study found.
Researchers used data from women participating in MESA (Multi-Ethnic Study of Atherosclerosis) who did not have CVD and had levels of testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) measured at baseline to examine associations with incident CVD, coronary heart disease (CHD), and heart failure events. Data were adjusted for demographic characteristics, risk factors for CVD, and use of hormone therapy. The study results were published online May 28 by the Journal of the American College of Cardiology and appear in the June 5 issue.
Overall, 2,834 postmenopausal women were included in the current study. Mean age was 64.9 years, and study participants were white, black, Hispanic, and Chinese. Assessment of CVD, CHD, and heart failure events was done via a telephone interview every 9 to 12 months, and most reported events were corroborated by hospital records. A total of 283 CVD events, 171 CHD events, and 103 heart failure events occurred over 12.1 years of follow-up. The fully adjusted hazard ratios associated with a 1-SD greater log-transformed total testosterone level were 1.14 (95% CI, 1.01 to 1.29) for CVD, 1.20 (95% CI, 1.03 to 1.40) for CHD, and 1.09 (95% CI, 0.90 to 1.34) for heart failure. For estradiol level and testosterone/estradiol ratio, the respective hazard ratios were 0.94 (95% CI, 0.80 to 1.11) and 1.19 (95% CI, 1.02 to 1.40) for CVD, 0.77 (95% CI, 0.63 to 0.95) and 1.45 (95% CI, 1.19 to 1.78) for CHD, and 0.78 (95% CI, 0.60 to 1.02) and 1.31 (95% CI, 1.01 to 1.70) for heart failure. No association was seen between dehydroepiandrosterone or SHBG levels and CVD outcomes.
The researchers noted that the number of events for some outcomes was limited, that some of the associations they observed might have been due to chance, and that levels of sex hormones were assessed only at baseline and were not measured during follow-up, among other limitations. However, they concluded that their results suggest an association between a higher testosterone/estradiol ratio and development of CVD, CHD, and heart failure events in postmenopausal women, as well as between higher estradiol level and a lower risk of CHD and heart failure.
“Sex hormone levels, especially higher total testosterone versus estrogen after menopause, may contribute to women's increased CVD risk later in life. However, in the absence of supportive interventional studies, the best strategy to modify sex hormone levels to affect CVD risk is still uncertain,” the authors wrote. “Nonetheless, a more androgenic sex hormone profile may identify a woman at higher risk for CVD who may benefit from other risk-reducing strategies.”
An accompanying editorial noted that variability in hormone profiles among individual women may be related to genetic variation in steroid metabolism affecting bioavailability of testosterone and estradiol and that the effects of these hormones on specific cardiovascular outcomes are related to other genetic differences. The editorialists called for more research into the way hormones affect development and progression of CVD among women as they age and said that observational research like the current study can provide information to help direct it.
“Defining cardiovascular risk for women should account for individualized profiles of genetic variants in enzymes associated with steroids metabolism, uptake, and receptors in conjunction with risk for specific cardiovascular pathologies,” they wrote. “This approach is precision medicine.”