Limb vascular function in women-Effects of female sex hormones and physical activity

Abstract

Throughout life, women are subjected to both acute fluctuations in sex hormones, associated with the menstrual cycle, and chronic changes following the onset of menopause. Female sex hormones, and in particular estrogen, strongly influence cardiovascular function such as the regulation of vascular tone and oxidative stress and thereby functions such as oxygen delivery and blood pressure. The acute hormonal fluctuations do not substantially impact health, but their influence should be considered with regard to measurements of vascular function. The chronic hormonal change with menopause strongly impacts the vasculature and markedly increases the risk of cardiovascular events. Physical activity activates signaling pathways also triggered by estrogen; therefore, exercise training could be an effective means of reducing the deleterious effects of estrogen loss at menopause. However, findings are divergent with some reporting marked improvements in vascular health with physical activity and others showing lower gains compared to age-matched males. Potential explanations for this discrepancy in findings are timing after menopause and training mode, aspects that should be further addressed in future studies. Physical activity should be recommended for women of all ages, but the most essential timing for maintenance of vascular health may be from menopause and onwards. K E Y W O R D Sblood vessel, estrogen, exercise, nitric oxide, prostacyclin | INTRODUCTIONFemale sex hormones, and in particular estrogen, are known to have numerous protective and functional roles in the vasculature including regulation of vasodilator systems, vascular growth, reduction in platelet reactivity, and vascular inflammation. 1,2 Alterations in the levels of sex hormones occur short term during the menstrual cycle and chronically at menopause with an almost complete loss of progesterone and estrogen. The chronic alterations in sex hormones at menopause greatly influence a number of aspects in women's health and substantially impact on the cardiovascular system resulting in impairment in vascular function 3,4 and a markedly increased prevalence of cardiovascular disease. 5 In this overview, we focus on how the short-term changes in sex hormones during the menstrual cycle and the chronic changes with menopause affect the vascular system in women. Focus lies primarily on basal regulation of vascular tone and the role of physical activity on the blood vessels supplying skeletal muscle tissue. After a brief overview of the physiology and molecular mechanisms underlying regulation of vascular tone, the influence of sex hormones is briefly addressed. We then discuss the effect of exercise and exercise training on vascular function during acute and chronic changes in female sex hormones, with an emphasis on estrogen. The main focus of this review was on humans but includes data from studies on laboratory animals and cell culture where relevant.

The exercise timing hypothesis: can exercise training compensate for the reduction in blood vessel function after menopause if timed right?

“…In the cardiovascular system, ERα has been described as being the primary receptor and most studies on the role of oestrogen in the cardiovascular system have examined the importance of ERα with less being known about the role of ERβ. The expression of ERα in venous endothelial cells fluctuates with the oestrogen levels during the menstrual cycle and the level of expression in older postmenopausal women is similar to that of the low oestrogen period (early follicular phase) of the menstrual cycle (Gavin et al 2009;Hellsten & Gliemann, 2018).…”

“…The expression of ERα in venous endothelial cells fluctuates with the oestrogen levels during the menstrual cycle and the level of expression in older postmenopausal women is similar to that of the low oestrogen period (early follicular phase) of the menstrual cycle (Gavin et al . ; Hellsten & Gliemann, ).…”

Effects of the menstrual and oral contraceptive cycle phases on microvascular reperfusion

“…Female endogenous and exogenous reproductive hormones, estrogen and progesterone, are known to fluctuate in concentration throughout the menstrual and oral contraceptive cycles, respectively. Estrogen, in particular, has been shown to play a significant role in the regulation of vasodilatory responses (Hellsten & Gliemann, 2018), suggesting (Gnasso et al, 2001). As measured with FMD, changes in conduit artery function across the menstrual cycle are inconsistent in the literature, with some studies showing increases in brachial artery FMD in the late follicular and midluteal phases of the menstrual cycle compared with the early follicular phase (Adkisson et al, 2010;English, Jacobs, Green, & Andrews, 1998;Harris, Tedjasaputra, Zhao, & Richardson, 2012;Hashimoto et al, 1995;Williams et al, 2001) and others reporting no change in FMD across the cycle (D'Urzo, King, Williams, Silvester, & Pyke, 2018;Jochmann et al, 2009;Rakobowchuk, Parsloe, Gibbins, Harris, & Birch, 2013;Saxena, Seely, & Goldfine, 2012;Shenouda, Priest, Rizzuto, & MacDonald, 2018).…”

“…Female endogenous and exogenous reproductive hormones, estrogen and progesterone, are known to fluctuate in concentration throughout the menstrual and oral contraceptive cycles, respectively. Estrogen, in particular, has been shown to play a significant role in the regulation of vasodilatory responses (Hellsten & Gliemann, ), suggesting that changes in estrogen concentrations across the menstrual and oral contraceptive cycle might alter vascular responsiveness. The assessment of vascular function across the menstrual and oral contraceptive cycles has been examined predominately using the well‐known, non‐invasive flow‐mediated dilatation (FMD) test.…”

Elevated shear rate‐induced by exercise increases eNOS ser1177 but not PECAM‐1 Tyr713 phosphorylation in human conduit artery endothelial cells

“…This study examined the activation of PECAM‐1 and eNOS in ECs collected from healthy, active males. Considering the well‐established benefits of oestrogen on endothelial function (Green et al, 2016; Hellsten & Gliemann, 2018), including post‐exercise vascular responses (Hellsten & Gliemann, 2018), it is possible that different mechanotransduction pathways may be apparent between sexes. As such, we only studied males to limit any influence of sex hormones on vascular responses.…”