Hormone Replacement Therapy and Cardiovascular Disease

Top Cited Papers
Publisher Website
Google Scholar
Abstract
For more than 50 million American women, and millions of women in other countries who are over the age of 50 years, the decision whether or not to use estrogen replacement therapy (ERT) for chronic disease prevention is often a difficult one. Established benefits of treatment for menopausal symptoms and prevention of osteoporosis must be weighed against documented risks of therapy, including venous thromboembolic events (VTE), gallbladder disease, and a possible increased risk of breast cancer. Unopposed ERT is also associated with an increased risk of endometrial cancer in women with a uterus. Therefore, it is typically combined with a progestin and is referred to as hormone replacement therapy (HRT). The impact of ERT/HRT on cardiovascular disease (CVD) is of great public health importance, because CVD is the leading cause of death and a major contributor to disability in women.1 The purpose of this advisory is to summarize the currently available data concerning potential CVD benefits and risks associated with ERT/HRT and to provide updated clinical recommendations regarding its use in the secondary and primary prevention of CVD. Mendelsohn and Karas2 recently reviewed the physiological effects of estrogen on the cardiovascular system. Briefly, cardiovascular cells, as well as reproductive tissues, bone, liver, and brain, express both of the known estrogen receptors, estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β). These receptors are important targets for endogenous estrogen, ERT, and pharmacological estrogen agonists. Estrogen–estrogen receptor complexes serve as transcription factors that promote gene expression with a wide range of vascular effects, including regulation of vasomotor tone and response to injury, that may be protective against development of atherosclerosis and ischemic diseases. Estrogen receptors in other tissues, such as the liver, may mediate both beneficial effects (eg, changes in apoprotein gene expression that improve lipid profiles) and adverse effects (eg, increases …