Increased estradiol levels have been found to be nonlinearly associated with all-cause mortality risk in elderly men, according to a recent study published in Clinical Endocrinology. The risk was slightly higher for cardiovascular disease and nonexistent for cancer mortality.
Researchers utilized data from a prospective cohort study to determine if estradiol levels affect all-cause and cause-specific mortality in older men (aged ≥65 years) and to assess whether estrogen receptor genetic polymorphisms modify the relationship with all-cause mortality.
The researchers followed 3650 men aged ≥65 years over a period of 12 years to evaluate the rate and cause of mortality. Of the 183 deaths that occurred during this period, 44 were due to cardiovascular disease, 57 were due to cancer, and 82 were due to other causes. For a random subsample of 495 participants with a history of coronary heart disease and documented triglyceride levels, total estradiol and free estradiol levels were measured and estrogen receptor genotyped.
Compared with men who survived, mean total and free estradiol levels were significantly higher in those who died. There was also a positive correlation between total and free estradiol levels (P <.001).
After adjusting for various factors, the researchers discovered a nonlinear quadratic relationship between all-cause mortality and total and free estradiol (p-quadratic =.04 and .05, respectively) among the subsample. These associations were found to be stronger for cardiovascular disease mortality (p-quadratic =.01 and .02); they did not exist for cancer mortality. Additionally, estrogen receptor genetic polymorphisms were found not to modify this association.
The researchers did note certain limitations to their findings, which included a potential for biased estimates caused by random sampling, as well as possibly inadequate methods for measuring estradiol levels.
These limitations notwithstanding, the researchers were confident their findings might open up new possibilities for further study. “These results could help improve our understanding of the role of estradiol in men’s health,” they conclude. However, “[the] mechanisms underlying these associations remain to be elucidated.”
Laouali N, Brailly-Tabard S, Helmer C, et al. Estradiol level, estrogen receptors, and mortality in elderly men: the three-city cohort study [published online June 23, 2018] Clinical Endocrinology. doi: 10.1111/cen.13797