Modulatory influence of sex hormones on vascular aging.

This review summarizes a presentation given during the "Countermeasures to Cardiovascular Aging Symposium" that was part of the American Physiological Society Conference on Cardiovascular Aging: New Frontiers and Old Friends held in Westminster, CO, in August 2017. Endothelial dysfunction, a characteristic of vascular aging, is a major risk factor for age-associated cardiovascular diseases. In women, the decline in endothelial function is attenuated until menopause, whereafter the rate of decline accelerates to match that seen in men. Sex differences in the decline in endothelial function have been attributed to changes in sex hormones with aging. Women have a progressive impairment in endothelial function across the stages of the menopause transition, related in part to declining estradiol levels. In contrast to women, little is known about the impact of declining testosterone levels on endothelial function in men. Some evidence suggests greater endothelial dysfunction in men with low testosterone compared with men with higher testosterone. The underlying causes of endothelial dysfunction with sex hormone deficiency are unknown but may be related to endothelial nitric oxide synthase dysfunction and oxidative stress. Lifestyle behaviors, including habitual endurance exercise, attenuates and reverses the age-associated decline in endothelial function in older men. However, in older women, these exercise adaptations are diminished or absent, possibly related to estrogen deficiency. Understanding how declines in sex hormones contribute to the vascular aging process in both women and men will inform effective sex-specific intervention strategies to preserve vascular health and prevent cardiovascular diseases.