Copyright © 2004, European Society of Cardiology
Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen
aCenter for Clinical Pharmacology, University of Pittsburgh, Pittsburgh, PA, United States
bDepartment of Obstetrics and Gynecology, Clinic for Endocrinology (D217, NORD-1), University Hospital Zurich, Frauenklinikstrasse-10, CH-8051, Zurich, Switzerland
cDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
dMedical-Policlinic, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland
eDepartment of Pharmacology, University of Pittsburgh, Pittsburgh, PA, United States
* Corresponding author. Department of Obstetrics and Gynecology, Clinic for Endocrinology (D217, NORD-1), University Hospital Zurich, Frauenklinikstrasse-10, CH-8051, Zurich, Switzerland. Tel.:+ 41 1 255 8608; fax: +41 1 255 4439. Email address: Raghvendra.dubey{at}usz.ch
Premenopausal women have a lower risk for cardiovascular events, and mortality due to coronary vascular disease (CVD) in premenopausal women is rare. These facts suggest that endogenous estrogens, such as estradiol, protect the cardiovascular system, and several observational studies and a few small clinical studies conducted in healthy and younger postmenopausal women support this hypothesis. In contrast, two large randomized clinical trials (RCTs), using conjugated equine estrogens and conducted in older women with established CVD or without overt CVD, failed to demonstrate protection against CVD by exogenous estrogens. These divergent findings have resulted in confusion with regard to the association between estrogen deficiency and CVD in postmenopausal women. In order to reconcile these contradictory findings, it is necessary to examine the pathophysiology associated with age-dependent changes within the vessel wall and to compare the pharmacology of different types of estrogens. Understanding age-dependent changes in vascular pathology and the pharmacology of different estrogens may facilitate the development of therapeutic strategies for hormone replacement therapy (HRT) that would be effective in delaying vascular remodeling leading to CVD following menopause. In this review we provide an overview of the impact of menopause and estrogen deficiency on vascular remodeling and emphasize the importance of timing and type of estrogen to achieve maximum benefits with regard to reducing the risk of CVD.
KEYWORDS Aging; Menopause; Hormone therapy; Estrogen; Cardiovascular disease
Time for primary review 15 days
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