Although aging impairs cardiovascular health in both men and women, the timeline is different between the sexes. This is at least partially attributed to the loss of estrogen in women at midlife, in connection with menopause. Estrogen has protective effects on the cardiovascular system, and menopause consequently leads to a rapid and significant decline in cardiovascular health. Notably, estrogen interacts with its nuclear and membrane receptors leading to changes in proteins of importance for cardiovascular health. Skeletal muscle activity, which affects the expression of many of the same proteins as estrogen, could potentially counteract the loss of estrogen at menopause. The hypothesis that exercise can counteract the loss of estrogen has been explored in several recent studies. It has been found that regular physical activity opposes the detrimental effects not only of aging, but also the menopausal transition, on cardiovascular health. Although, vascular benefits can be gained at all ages, initiating physical activity at or soon after menopause may be more effective than at a later time point in life. Intuitively, it is easier to prevent decrements than attempting to regain lost vascular health. This idea is supported by evidence at the molecular level, suggesting that exercise-induced activation of the estrogen-related receptor-α pathway is more effective soon after menopause compared to later. Together, although a decline in cardiovascular health due to chronological aging cannot be completely prevented, a physically active lifestyle mitigates age-related cardiovascular impairments. Importantly, regular physical activity through life should always be addressed as the biological norm.