Hormones and cardiovascular disease in older men

Older men have lower circulating testosterone (T) and insulin-like growth factor-I (IGF-I) but higher levels of thyrotrophin (TSH) compared with younger men, and exhibit poorer health. Whether age-associated differences in hormone levels are causally related to cardiovascular disease, or are biomarkers reflecting accumulated ill-health remains under debate. Lower T levels are associated with aortic, peripheral vascular, and cardiovascular disease in middle-aged and older men. In some but not all studies, lower levels of T predict increased incidence of cardiovascular events and mortality. Recently, dihydrotestosterone (DHT) has also been identified as a predictor for peripheral vascular and ischemic heart disease. Small scale randomized clinical trials (RCTs) of T supplementation suggest a protective effect against myocardial ischemia in men with coronary artery disease. There have been no RCTs with the prespecified outcomes of cardiovascular events or mortality. One RCT of T in older men with mobility limitations was stopped due to an excess of cardiovascular adverse events in men receiving T, but other RCTs have not raised similar concerns. Observational studies of testosterone supplementation have reported contrasting results. Levels of IGF-I and its binding proteins 1 and 3 have been variably associated with mortality in some but not all studies, and RCTs of interventions to modulate IGF-I levels are either lacking or lacking in power to examine outcomes of cardiovascular events or mortality. Subclinical hyper- and hypothyroidism predict poorer outcomes, and emerging data implicate higher levels of free thyroxine with other outcomes such as dementia and mortality in older men. However, RCTs that manipulate free thyroxine levels within the normal range are lacking and would be challenging to perform. Further research is needed to clarify the role of these hormones as predictors of cardiovascular outcomes in aging men, and to test whether interventions that modulate levels of T, DHT, IGF-I or free thyroxine would reduce cardiovascular morbidity and mortality.