Vasomotor and vascular effects of hormone replacement therapy.
Cardiovascular risk factors impair endothelium-dependent vasodilation as well as other functions of the endothelium, thereby predisposing the patient to atherosclerosis and its overt clinical manifestations. Loss of endogenous estrogen also leads to reduced bioavailability of endothelium-derived nitric oxide. In premenopausal women, the impairment of endothelial function develops within 1 month of surgical ovariectomy and is reversed by the administration of exogenous 17 beta-estradiol. Exogenous estrogen administration restores endothelial function by enhancing nitric oxide synthesis through genomic and nongenomic mechanisms and by reducing oxidative stress and nitric oxide breakdown. The effect of progesterone on endothelial function is still under investigation. In animal studies, medroxyprogesterone acetate (MPA) counteracts estrogen's beneficial effects on endothelial function and on coronary plaque size. In humans, however, the addition of progesterone to estradiol does not appreciably attenuate estrogen-associated endothelium-dependent vasodilation. Secondary prevention trials with conjugated equine estrogen plus MPA have no proven benefit in reducing coronary events, progression of angiographic coronary atherosclerosis, or incidence of cerebrovascular events. This suggests that beneficial effects of estrogen on endothelial function are counterbalanced by detrimental effects, perhaps because of proinflammatory and prothrombotic actions. The selective estrogen receptor modulators are currently under investigation as agents that might retain the favorable, without possessing the unfavorable, effects of estrogen on the vascular system.
Ganz
Peter
P
Harvard School of Medicine, Cardiac Catheterization Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
D000818:Animals; D001916:Brachial Artery / Q000502:physiology; D002318:Cardiovascular Diseases / Q000503:physiopathology / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000187:drug effects; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III; D011673:Pulsatile Flow / Q000187:drug effects; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D017258:Medroxyprogesterone Acetate; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III