The effects of oestrogens and their receptors on cardiometabolic health

Abstract

Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. The incidence of CVD is sexually dimorphic, and research has focused on the contribution of sex steroids to the development and progression of the cardiometabolic syndrome, which is defined as a clustering of interrelated risk factors that promote the development of atherosclerosis (which can lead to CVD) and type 2 diabetes mellitus. Data are inconclusive as to how sex steroids and their respective receptors increase or suppress the risk of developing the cardiometabolic syndrome and thus CVD. In this Review, we discuss the potential role, or roles, of sex hormones in cardiometabolic health by first focusing on the influence of oestrogens and their receptors on the risk of developing cardiometabolic syndrome and CVD. We also highlight what is known about testosterone and its potential role in protecting against the development of the cardiometabolic syndrome and CVD. Given the inconclusive nature of the data regarding the direct effects of each sex hormone, we advocate and highlight the importance of studying the relative levels and the ratio of sex hormones to each other, as well as the use of cross sex hormone therapy and its effect on cardiometabolic health.

Cardiovascular Disease in Type 2 Diabetes: A Review of Sex-Related Differences in Predisposition and Prevention

“…It is worth mentioning that estrogens reduce the expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 by endothelial cells via nongenomic mechanisms and participate in maintaining the endothelial function. 109 von Willebrand factor has been linked to the development of CVD and cardiovascular mortality in people with T2DM, whereas E-selectin was found to be associated with CVD in those people but none of these results were stratified by sex.…”

“…In fact, menopausal transition is associated with increased adiposity and changes in fat distribution, which contributes to insulin resistance and T2DM although the impact of estrogens' loss per se on the incidence of T2DM remains unclear. 109,123 Other highrisk groups include women with gestational diabetes and those with polycystic ovary syndrome. Interestingly, these 2 latter conditions represent 2 natural models of hyperglycemia and insulin resistance (the mechanisms at interplay in T2DM) that could help to understand the pathogenesis of the increased cardiovascular risk in women with T2DM.…”

Peer Review #1 of "Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women (v0.1)"

“…298 Moreover, linkage disequilibrium between these two polymorphisms with other polymorphisms 299 in the ESR1 gene, such as TA tandem polymorphism in the promoter region could affect gene 300 expression or function (Herrington et al 2002). Polymorphisms in ESR1 were first thought to be 301 potential risk factors for the development of CVD; but a meta-analysis including 10 case-control 302 studies demonstrated that the ESR1 SNPs PvuII and XbaI are not associated with risk of CVD 303 (Morselli et al 2017). In this study we have noted an inverse trend between these polymorphisms 304 and risk of CVD in diabetic group.…”

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

“…Several beneficial physiological effects of estrogen on vascular function, atherosclerosis, lipoprotein metabolism and cardiomyocyte protection are proposed (Morselli et al 2017). In an uncontrolled study of oral E 2 (0.5, 1 or 2 mg daily) for 9 weeks in 22 healthy elderly men, lipid parameters improved from baseline (Giri et al 1998).…”

“…E 2 -but not placebo-treated men showed reduced vasoconstrictor responses to angiotensin II and norephinephrine, enhanced endothelial basal nitric oxide release, and reductions in systolic and diastolic blood pressure. Additionally, there are a range of proposed cellular mechanisms by which estrogens may be important for cardiomyocyte protection in the context of ageing, insulin resistance, hypertension and ischaemia (Morselli et al 2017).…”