Estrogen, cardiac protection and aging

Estrogen loss and aging are inexorably linked. 17β-Estradiol (E2) can protect the heart from injury, but its effects are reduced in aging. Aging and estrogen loss contribute to a pro-inflammatory state and a decreased ability to handle ROS. This is further complicated by loss of the protective heat shock response with aging. E2 has many protective properties, including reducing cardiac injury and protecting the mitochondria, but the confounding effects of aging have not been well studied. E2 has a positive impact on pathologic cardiac hypertrophy and there are distinct differences in the roles of ERα and ERβ in hypertrophy, but whether this persists with aging is unknown. Clinically, postmenopausal women have an acceleration of atherosclerosis. Unexpectedly, double-blind randomized clinical trials of hormone replacement therapy (HRT) showed increased cardiovascular events and cancer with HRT. However HRT was initiated on average 10 years postmenopause and this likely contributed to the increase in cardiovascular events. Although our understanding of estrogen has come far over the last 20 years, much more basic research is needed to understand the consequences of aging and estrogen loss.