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Endothelial dysfunction and menopause: is exercise an effective countermeasure?

Climacteric. 2018 Jun;21(3):267-275.

Endothelial dysfunction and menopause: is exercise an effective countermeasure?

Witkowski S1, Serviente C2.

Author information 1a Department of Exercise and Sport Studies , Smith College , Northampton , MA , USA.2b Department of Kinesiology , University of Massachusetts Amherst , Amherst , MA , USA.

Abstract Cardiovascular disease is the leading cause of death in women. There is a dramatic rise in risk factors for cardiovascular disease during the menopausal transition that is independent of aging. Endothelial dysfunction is an early hallmark of developing cardiovascular disease and has been shown to increase across the stages of menopause. Exercise is considered one of the most effective lifestyle therapies to maintain and improve endothelial function. However, accumulating evidence suggests that exercise does not have the same benefit on endothelial function in menopausal women as it does in other populations, and factors associated with menopause likely influence the endothelial responsiveness to exercise. This review will detail the current available evidence on endothelial dysfunction, exercise, and menopause, including mechanisms that may mediate the accumulating endothelial dysfunction in women with menopause, the impact of exercise on endothelial function in women, and whether regular exercise is an effective therapeutic and prevention strategy to maintain endothelial function with menopause. We conclude that the effect of exercise on endothelial function differs according to menopausal stage and cardiovascular disease risk burden. Finally, we will address critical gaps in the literature with the goal of identifying future research directions to improve healthy aging in women.

KEYWORDS: Endothelial function; cardiovascular disease; exercise; menopause; nitric oxide Menopause. 2018 Apr 9. doi: 10.1097/GME.0000000000001112. [Epub ahead of print] Vascular dysfunction across the stages of the menopausal transition is associated with menopausal symptoms and quality of life. Hildreth KL1, Ozemek C2, Kohrt WM1,3, Blatchford PJ4, Moreau KL1,3. Author information 1Department of Medicine, Division of Geriatric Medicine, University of Colorado School of Medicine, Aurora, CO.2Department of Physical Therapy and the Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL.3Eastern Colorado VA Geriatric Research, Education and Clinical Center, Denver, CO.4Colorado Biostatistical Consortium, Colorado School of Public Health, University of Colorado Denver, Denver, CO. Abstract OBJECTIVE: The menopausal transition is associated with somatic symptoms and increased rates of depression, which can impair quality of life (QOL) and increase cardiovascular disease (CVD) risk. This period is also associated with accelerated vascular aging (arterial stiffening and endothelial dysfunction), an antecedent to CVD. This secondary analysis sought to explore associations between depression, menopausal symptoms and QOL, and vascular aging across menopause stages. METHODS: Arterial stiffness (carotid artery compliance), endothelial function (brachial artery flow-mediated dilation [FMD]), menopausal symptoms (Menopausal Symptom List [MSL]), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), and QOL (Utian QOL Scale [UQOL]) were measured in 138 women (19-70 years) classified as premenopausal (n = 41, 34 ± 8 years; mean ± SD), early (n = 25, 49 ± 3 years), or late perimenopausal (n = 26, 50 ± 4 years), or early (n = 22, 55 ± 4 years) or late postmenopausal (n = 24, 61 ± 5 years). Differences across menopause stages were determined using one-way analysis of variance; associations between vascular measures and MSL, CES-D, and UQOL were tested using Pearson’s correlation analyses. RESULTS: Menopausal symptoms, depression, and QOL worsened across menopause stages, particularly in late perimenopausal women. Vasosomatic symptom frequency, and general somatic symptom frequency and severity were inversely correlated with carotid artery compliance and FMD (r = -0.27 to -0.18, all P < 0.05). Only correlations with general somatic symptoms were significant after adjusting for multiple comparisons. Total QOL was positively correlated with carotid artery compliance (r = 0.23, P = 0.01). CES-D scores were not correlated with carotid artery compliance or FMD (r = -0.08, -0.03, P = 0.35). CONCLUSIONS: Vascular dysfunction across the stages of menopause was associated with greater frequency and severity of menopausal symptoms, and lower QOL, but not depression. Mechanisms underlying these associations (eg, inflammation, oxidative stress) should be explored. BMC Med. 2017 Jan 4;15(1):2. doi: 10.1186/s12916-016-0762-8. Unraveling the associations of age and menopause with cardiovascular risk factors in a large population-based study. de Kat AC1,2, Dam V2, Onland-Moret NC2, Eijkemans MJ2, Broekmans FJ1, van der Schouw YT3. Author information 1Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3508 GA, The Netherlands.2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3508 GA, The Netherlands.3Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3508 GA, The Netherlands. Erratum in

  • Erratum to: Unraveling the associations of age and menopause with cardiovascular risk factors in a large population-based study. [BMC Med. 2017]

Abstract BACKGROUND: Although the association between menopause and cardiovascular disease (CVD) risk has been studied extensively, the simultaneous role of chronological aging herein remains underexposed. This study aims to disentangle the relationships of menopausal status and chronological aging with CVD risk factors in the largest study population to date. METHODS: In this cross-sectional study, CVD risk factors were compared between women with a different menopausal status within the same yearly age strata. The study population comprised female participants of the baseline visit of the population-based LifeLines Cohort Study. A total of 63,466 women, aged between 18 and 65 years, was included. Of them, 39,379 women were considered to be premenopausal, 8669 were perimenopausal, 14,514 were naturally postmenopausal, and 904 were surgically postmenopausal. RESULTS: Compared to postmenopausal women aged 45 years, average total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) were 0.5 and 0.4 mmol/L higher, respectively, in postmenopausal women aged 50. Systolic and diastolic blood pressure levels were 4 and 1 mmHg higher, respectively. At all ages between 46 and 55 years, and after adjustment for confounders, naturally postmenopausal women had 0.2 to 0.4 mmol/L higher TC and 0.1 to 0.3 mmol/L higher LDL-c levels compared to premenopausal women in the same age range. Systolic blood pressure levels were up to 4 mmHg lower in naturally post- compared to premenopausal women at all ages between 29 and 52 years. Body mass index levels were up to 3.2 kg/m2 higher in women with surgical menopause compared to all other women between the ages 32 and 52 years. All aforementioned results were statistically significant. CONCLUSIONS: Chronological age and menopausal status are both independently associated with CVD risk factors. Based on the comparatively smaller observed differences associated with menopausal status than with chronological aging, the significance of a more unfavorable lipid profile in a later reproductive stage may be less obvious than previously thought. KEYWORDS: C

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