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Review
, 125 (6), 1881-1887

Intersection Between Gonadal Function and Vascular Aging in Women

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Review

Intersection Between Gonadal Function and Vascular Aging in Women

Kerrie L Moreau. J Appl Physiol (1985).

Abstract

Vascular aging, characterized by endothelial dysfunction and large elastic arterial stiffening, is a major risk factor for age-associated cardiovascular disease (CVD). Although women have a lower prevalence of CVD until midlife, prevalence rates increase rapidly coincident with the menopausal transition to match those observed in men. The menopausal transition, or perimenopause, is a chaotic period that is associated with increased symptoms (e.g., hot flashes, depressed mood, anxiety, sleep disturbances) and CVD risk factors due to changes in the hormonal environment. Because these quality of life factors and CVD risk factors also change with aging, the arteries of women appear to endure a double insult. Our laboratory has been investigating how changes in gonadal function and hormone levels with the menopause transition impacts the vascular aging process in healthy women. Our work has shown that vascular endothelial function progressively declines, and large elastic arterial stiffness is greater across the stages of the menopausal transition. This acceleration in vascular aging may be due to the loss of vasodilatory, antioxidant, anti-inflammatory, and antiproliferative effects of estradiol on the vascular wall. This minireview discusses the impact of changes in gonadal function and hormones with the menopausal transition on vascular aging in women and areas for investigations to further our understanding of the intersection between gonadal function and vascular aging.

Keywords: aging; sex hormones; vascular biology; women.

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the author.

Figures

Fig. 1.
Fig. 1.
Gonadal function and vascular aging across the stages of the menopausal transition. The decline in endothelial function [brachial artery flow-mediated dilation (FMD), bottom] accelerates in late perimenopausal women, coincident with declines in mean estradiol (E2) and elevated follicle-stimulating hormone (FSH) concentrations (top) (29). The decline in large elastic artery compliance (carotid artery compliance) is mediated largely by aging; however, changes in gonadal function likely contibute to this process (15). Pre, premenopausal; Peri, early- and late-perimenopausal, Post, postmenopausal.
Fig. 2.
Fig. 2.
Schematic of vascular aging across the menopausal transition in women. Vascular aging, including vascular endothelial dysfunction and large elastic artery stiffening, increases the risk for age-associated cardiovascular disease (CVD) in that it combines with other known risk factors (e.g., increased adiposity, cholesterol, depression). In women, arteries are also exposed to increased risk factors (i.e., increased adiposity, cholesterol, depression) during the menopause transition when they are vulnerable to damage mediated by changes in the hormonal environment. Changes in the hormonal milieu during the menopause transition may be associated with a prooxidant, proinflammatory phenotype due to a shift in redox balance and inflammatory cytokines in the late perimenopausal to early postmenopausal period. Excessive reactive oxygen species (ROS) and inflammatory cytokines impair endothelial function and increases arterial stiffness by scavenging nitric oxide (NO) and decreasing its biosynthesis by oxidizing endothelial nitric oxide synthase (eNOS) and its cofactors [i.e., tetrahydrobioptern (BH4)], resulting in uncoupled eNOS, which produces more ROS. ROS and inflammatory cytokines also contribute to arterial stiffening by altering arterial wall structure, including intimal thickening, elastin fragmentation, collagen and extracellular matrix deposition. TNFα, tumor necrosis factor-α.

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