Format

Send to

Choose Destination
Adv Pharmacol. 2016;77:307-60. doi: 10.1016/bs.apha.2016.05.003. Epub 2016 Jun 29.

Estrogens and Coronary Artery Disease: New Clinical Perspectives.

Author information

1
Triemli City Hospital, Zürich, Switzerland. Electronic address: matthias.meyer@triemli.zuerich.ch.
2
Molecular Internal Medicine, University of Zürich, Zürich, Switzerland. Electronic address: barton@access.uzh.ch.

Abstract

In premenopausal women, endogenous estrogens are associated with reduced prevalence of arterial hypertension, coronary artery disease, myocardial infarction, and stroke. Clinical trials conducted in the 1990s such as HERS, WHI, and WISDOM have shown that postmenopausal treatment with horse hormone mixtures (so-called conjugated equine estrogens) and synthetic progestins adversely affects female cardiovascular health. Our understanding of rapid (nongenomic) and chronic (genomic) estrogen signaling has since advanced considerably, including identification of a new G protein-coupled estrogen receptor (GPER), which like the "classical" receptors ERα and ERβ is highly abundant in the cardiovascular system. Here, we discuss the role of estrogen receptors in the pathogenesis of coronary artery disease and review natural and synthetic ligands of estrogen receptors as well as their effects in physiology, on cardiovascular risk factors, and atherosclerotic vascular disease. Data from preclinical and clinical studies using nonselective compounds activating GPER, which include selective estrogen receptor modulators such as tamoxifen or raloxifene, selective estrogen receptor downregulators such as Faslodex™ (fulvestrant/ICI 182,780), vitamin B3 (niacin), green tea catechins, and soy flavonoids such as genistein or resveratrol, strongly suggest that activation of GPER may afford therapeutic benefit for primary and secondary prevention in patients with or at risk for coronary artery disease. Evidence from preclinical studies suggest similar efficacy profiles for selective small molecule GPER agonists such as G-1 which are devoid of uterotrophic activity. Further clinical research in this area is warranted to provide opportunities for future cardiovascular drug development.

KEYWORDS:

Artery; Atherosclerosis; Blood pressure; Cholesterol; Clinical medicine; Coronary artery disease; Drug therapy; Dyslipidemia; Endothelium; Estrogen; Faslodex™; Fulvestrant; GPER; GPER-1; GPR30; Heart; Hormone replacement therapy; Hormone therapy; Hormones; Hypertension; ICI 182,780; Inflammation; Menopause; Myocardium; Niacin; Nitric oxide; Obesity; Patients; Personalized medicine; Risk factors; Tamoxifen; Theranostics; Vascular

PMID:
27451102
DOI:
10.1016/bs.apha.2016.05.003
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center