Cardiovascular Disease Risk and Menopause: Effects of Cardiorespiratory Fitness, Exercise, and Follicle Stimulating Hormone

Menopause is associated with adverse changes in cardiovascular disease risk factors. A reduction in estrogens is most commonly associated with changing cardiovascular disease risk; however, recent observations suggest that the increase in follicle stimulating hormone that accompanies menopause may also influence risk, potentially through its influence on lipid levels. The changes in cardiovascular disease risk factors may adversely affect endothelial cell function, a pre-clinical marker for cardiovascular disease. Whether cardiorespiratory fitness is protective of endothelial health in this population, thereby mitigating the changes in risk that accompany menopause, is unclear. This dissertation evaluated differences in endothelial health and endothelial responses to acute exercise in women in various menopausal stages and with different levels of cardiorespiratory fitness. Endothelial health was assessed using flow-mediated dilation and endothelial microparticles (EMPs). The project also evaluated whether follicle stimulating hormone (FSH) levels were related to lipid levels in a large cohort of postmenopausal women. We found that: 1) endothelial function declines with menopause, independent of cardiorespiratory fitness, 2) EMPs are reduced with acute, moderate intensity exercise in midlife women, despite differences in menopausal status and cardiorespiratory fitness, 3) High FSH is related to dyslipidemia in postmenopausal women. Together, these data suggest that menopause and cardiorespiratory fitness differentially impact factors related to cardiovascular disease risk

Follicle-Stimulating Hormone is Associated with Lipids in Postmenopausal Women

Objective: The purpose of this study was to evaluate the relation between FSH and lipid levels in postmenopausal women from the Kuopio Ischaemic Heart Disease Risk Factor Study. Methods: Postmenopausal women (n = 588) aged 53 to 73 years and not using hormone therapy were included. The relation between FSH and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) was evaluated using linear regression, adjusting for estradiol, body mass, smoking, and other hormonal and lifestyle factors. The relation between FSH, dyslipidemia, and abnormal lipid levels were also evaluated. Results: FSH was positively and linearly associated with TC (P = 0.001) and LDL-C (P = 0.01) in all participants, with stronger relations seen in younger compared with older postmenopausal women. FSH was less strongly associated with HDL-C and TG. FSH was not associated with dyslipidemia; however, higher FSH was associated with increased risk of high TC (P = 0.02) and high LDL-C (P = 0.03). Conclusions: These data suggest that higher FSH in postmenopausal women is related to higher levels of both TC and LDL-C

Follicle-Stimulating Hormone, but not Cardiorespiratory Fitness, is Associated with Flow-Mediated Dilation with Advancing Menopausal Stage

Objective:The aim of the study was to evaluate if there are differences in endothelial function before and after acute exercise in women at different menopausal stages with high and low cardiorespiratory fitness.Methods:Participants were healthy high-fit premenopausal (n = 11), perimenopausal (n = 12), and postmenopausal women (n = 13) and low-fit perimenopausal (n = 7) and postmenopausal women (n = 8). Brachial artery flow-mediated dilation (FMD) was measured before and after acute moderate intensity exercise. FMD was calculated as (Diameterpeak-Diameterbaseline)/ Diameterbaseline) × 100. Differences between high-fit women and between high- and low-fit perimenopausal and postmenopausal women were assessed with repeated-measure ANOVAs. Relations with FMD were assessed with Pearson correlations.Results:FMD was reduced with progressive menopausal stage in high-fit women (P = 0.005) and was lower in perimenopausal compared to postmenopausal women (P = 0.047). FMD was lower in high-fit compared to low-fit women (P = 0.006) and there was no relation between FMD and VO2peak (P \u3e 0.05). There was an inverse relation between FMD and follicle-stimulating hormone (P \u3c 0.05), but not estradiol (P \u3e 0.05).Conclusions:These data suggest that endothelial function is lower with progressive menopausal stage in women with high cardiorespiratory fitness; that FMD is lower in women with higher cardiorespiratory fitness; and that FSH, but not estradiol, is associated with FMD

Moderate-Intensity Exercise Reduces Activated and Apoptotic Endothelial Microparticles in Healthy Midlife Women

Endothelial microparticles (EMPs) are related to cardiovascular disease (CVD) risk. Risk factors for CVD increase with menopause, and greater cardiorespiratory fitness is generally expected to reduce CVD risk. The effects of habitual physical activity on endothelial health may be due in part to the effect of acute exercise on circulating EMPs. This study was performed to evaluate the effect of an acute bout of exercise on CD62E+ and CD31+/42b- EMPs in healthy fit midlife women at different menopausal stages. Healthy, active premenopausal (PRE), perimenopausal (PERI), and postmenopausal (POST) women completed a single bout of moderate-intensity treadmill exercise. Activated (CD62E+) and apoptotic (CD31+/42b-) EMPs were evaluated before and 30 min after exercise by using fluorescent activated cell sorting. In an exploratory analysis, these results were compared with data from low-fit peri- and postmenopausal women. Differences by group and time point were evaluated with repeated-measure ANOVAs. There was a reduction in the number of total microparticles ( P \u3c 0.001), CD62E+ ( P = 0.003), and CD31+/42b- ( P \u3c 0.001) EMPs/μl plasma following acute exercise. The percentage of CD62E+ EMPs increased with acute exercise ( P \u3c 0.001), whereas the percentage of CD31+/42b- EMPs did not change ( P = 0.40). There was no effect of menopausal status on CD62E+or CD31+/42b- EMPs, or on total microparticles (all P \u3e 0.05). The exploratory analysis revealed that low-fit women had similar changes in EMPs with acute exercise. We concluded that acute moderate-intensity exercise reduces CD62E+and CD31+/42b- EMPs, as well as total microparticles, in healthy midlife women. These effects occurred despite differences in menopausal status and fitness. NEW & NOTEWORTHY This study demonstrates that acute moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women

Endothelial and Inflammatory Responses to Acute Exercise in Perimenopausal and Late Postmenopausal Women

Endothelial dysfunction and inflammation are characteristics of subclinical atherosclerosis and may increase through progressive menopausal stages. Evaluating endothelial responses to acute exercise can reveal underlying dysfunction not apparent in resting conditions. The purpose of this study was to investigate markers of endothelial function and inflammation before and after acute exercise in healthy low-active perimenopausal (PERI) and late postmenopausal (POST) women. Flow-mediated dilation (FMD), CD31+/CD42b- and CD62E+ endothelial microparticles (EMPs), and the circulating inflammatory factors monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), and tumor necrosis factor-α (TNF-α) were measured before and 30 min after acute exercise. Before exercise, FMD was not different between groups (PERI: 6.4 ± 0.9% vs. POST: 6.5 ± 0.8%, P = 0.97); however, after acute exercise PERI tended to improve FMD (8.5 ± 0.9%, P = 0.09), whereas POST did not (6.2 ± 0.8%, P = 0.77). Independent of exercise, we observed transient endothelial dysfunction in POST with repeated FMD measures. There was a group × exercise interaction for CD31+/CD42b- EMPs (P = 0.04), where CD31+/CD42b- EMPs were similar before exercise (PERI: 57.0 ± 6.7 EMPs/µl vs. POST: 58.5 ± 5.3 EMPs/µl, P = 0.86) but were higher in POST following exercise (PERI: 48.2 ± 6.7 EMPs/µl vs. POST: 69.4 ± 5.3 EMPs/µl, P = 0.023). CD62E+ EMPs were lower in PERI compared with POST before exercise (P \u3c 0.001) and increased in PERI (P = 0.04) but did not change in POST (P = 0.68) in response to acute exercise. After acute exercise, MCP-1 (P = 0.055), TNF-α (P = 0.02), and IL-8 (P \u3c 0.001) were lower in PERI but only IL-8 decreased in POST (P \u3c 0.001). Overall, these data suggest that perimenopausal and late postmenopausal women display different endothelial and inflammatory responses to acute exercise