Changing Sex Hormones Represent a Cardiovascular Disadvantage for Aging Women

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The cardioprotective effects of estrogens are considered a female advantage in premenopausal women. However, the decline in circulating estrogens that occurs during the menopausal transition is associated with rapid and adverse changes in cardiovascular disease (CVD) risk factors. For example, there is an age-independent increase in blood pressure and plasma lipids during perimenopause (4). Given that women will spend one third or more of their lives in menopause, it is important to discover the underlying mechanisms behind this increase in CVD risk and whether it can be attenuated or prevented.
In this issue of Exercise and Sport Sciences Reviews, Moreau and Ozemek (6) present evidence for the hypothesis that sex hormones, such as estrogens, play a permissive role in endothelial adaptations to endurance exercise training in healthy older women and propose potential mechanisms for this effect. The implication is that women with reductions in natural estrogens, such that occur during the menopausal transition, do not respond to exercise training with the same improvement in endothelial function as men. Understanding endothelial dysfunction in women is important for three reasons. First, it is a subclinical marker for CVD and therefore can be used to identify early changes in CVD risk. Second, endothelial dysfunction is significantly related to cardiovascular events. Finally, an accurate assessment of CVD risk in women may not come from traditional risk factors, as a high prevalence of atherosclerosis has been detected in postmenopausal women with low-moderate CVD risk measured by conventional risk factors (5) Therefore, other nontraditional markers, such as endothelial function, may be better indicators of CVD risk in aging women.
The length of estrogen exposure during a woman's reproductive years affects cardiovascular outcomes and therefore may be an important variable to consider when assessing vascular health. Women who undergo menopause at an age of 52 yr are 18% less likely to die from CVD than women who go through menopause at 44 years old (1). Women who go through menopause at a later age are also more likely to live longer (7). Furthermore, women with high estrogen levels before and a rapid decrease after their final menstrual period are 43% less likely to develop atherosclerosis than women who have chronically low levels of estrogen, independent of CVD risk factors (2). Together, these data suggest that women who have a longer length of estrogen exposure have better cardiovascular outcomes.
Exercise is an effective therapy to prevent and treat CVD; however, significant sex differences exist in the response of select CVD risk factors to exercise training, with a more favorable effect of training in men (3). In light of the evidence compiled by Moreau and Ozemek (6), the role of exercise to prevent and treat CVD in women must continue to be explored. An improvement in the evidence base has the potential to affect recommendations for exercise, stimulate the development of novel CVD prevention approaches, and inform decisions regarding health and health care for women.
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