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Query: UMLS:C0018799 (heart disease)
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The potential long-term benefits of estrogen replacement therapy (ERT) in the prevention of osteoporosis and heart disease have been reasonably well established. However, the favorable effects of ERT on cognitive function and prevention of senile dementia in old age now represents a revitalized area of clinical research. A growing body of experimental evidence has recently provided the neurobiologic basis to support the hypothesis that gonadal hormones such as estrogen have psychologic effects on human brain function and behavior. Studies in women who have undergone surgical menopause have demonstrated that the menopause is associated with subclinical cognitive and affective dysfunction, which is improved by ERT. In addition, a growing body of evidence suggests that estrogen may be an effective therapy for senile dementia in some elderly women. Recent epidemiologic studies have indicated that long-term postmenopausal ERT may prevent late-life cognitive dysfunction in older women. Several clinical trials employing oral estrogen therapy have also observed that some aged women with senile dementia have improved cognitive and affective function after estrogen therapy. Estrogen loss resulting in cognitive disorders, including menopausal cognitive dysfunction and senile dementia in late life, may act via several mechanisms. Estrogen may be an important growth factor for estrogen-responsive neurons. Estrogen therapy may also have substantial neurochemical effects, direct effects on the vasculature, and effects on the generation of free radicals, which may be toxic to neurons. At this time, several important clinical questions need to be answered regarding the role of ERT in the cognitive and affective dysfunctions associated with menopause and senile dementia. Should estrogen be used for menopausal women whose sole complaint is cognitive or affective dysfunction? Does long-term ERT prevent cognitive decline in late life if initiated at the time of menopause? Can ERT improve cognition and affective function in postmenopausal women with Alzheimer's disease, and does estrogen therapy prevent the progression of Alzheimer's disease in these patients? Finally, do the vascular effects of estrogen play a role in the treatment or prevention of both Alzheimer's disease and vascular dementia?
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PMID:Future therapeutic developments of estrogen use. 853 Jul 15

A woman spends about one-third of her life in her postmenopausal years. Some women supplement this period of decreased estrogen production with estrogen replacement therapy (ERT). Since the 1970s, we have evaluated the long-term risks and benefits of ERT in one population of women, the Leisure World retirement community. ERT is the most effective method for preventing osteoporotic bone loss and fractures in postmenopausal women. In Leisure World, ERT reduced the risk of hip fractures about 50 %. The effect is greatest in long-term users but may be lost after discontinuation. Postmenopausal osteoporosis affects the bones of the jaws as well as other skeletal bones. Bone loss in the jaws may result in tooth loss. In Leisure World, estrogen users retain more natural teeth than nonusers. Cardiovascular disease is the leading cause of hospitalization and death in women. In Leisure World, ERT reduced the risk of fatal and nonfatal myocardial infarction, ischemic heart disease, other heart disease, and stroke by 20-40 %. The reduction is greatest in long-term and/or current users. ERT is effective in women with and without cardiovascular disease risk factors. A most feared aspect of aging is Alzheimer's disease. In Leisure World, women who had used ERT had a reduced risk of Alzheimer's disease. Risk both increaseng dose and decreased with increasing duration of use. Estrogen use, however, is not without risk. Unopposed estrogen increases risk of endometrial cancer. Risk increases with increasing years of use and remains high after discontinuation. The most important potential risk of ERT is breast cancer. In Leisure World, women who had used a total accumulated estrogen dose of 1500 mg or more had nearly twice the risk of breast cancer compared with nonusers. Short-term low-dose users showed no substantial increased risk. The Leisure World Study shows risks and benefits of ERT similar to other reports in the literature. For postmenopausal women generally, the benefits of ERT--preventing osteoporotic fractures, reducing heart disease, decreasing mortality, and possibly reducing risk of Alzheimer's disease-out-weigh the risks of endometrial and breast cancers. A woman must be fully informed of the risks and benefits of hormone therapy and play an important role in deciding whether to take hormones and which regimen to use.
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PMID:Estrogen replacement therapy in the elderly. 870 21

A protective effect of estrogen is the most obvious reason for the substantial and consistent favored status of women vs. men with regard to coronary heart disease (CHD). This paper briefly reviews the history of studies of the estrogen-heart disease hypothesis, the reason why clinical trials of postmenopausal estrogen are necessary (despite the strength, consistency, and plausibility of the 'protection' seen in observational studies), and the status of the 'Postmenopausal Estrogen/Progestin Interventions' (PEPI) trial results and ongoing trials. The potential for nonhormonal primary prevention is emphasized.
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PMID:Postmenopausal estrogen and heart disease. 882 60

Estrogen replacement therapy is becoming an important weapon in the fight against osteoporosis and heart disease in postmenopausal women, in addition to its original role of alleviating many of the symptoms associated with menopause. Dr. Connell discusses the many benefits of estrogen replacement therapy and the advantages that transdermal administration of estrogen appear to offer over other routes of administration.
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PMID:Transdermal estrogen therapy. 919 69

In recent years, reports of favourable effects of estrogen therapy on cardiovascular morbidity and mortality have led to enthusiasm for widespread use of estrogens by postmenopausal women. Guidelines for estrogen therapy issued by the American College of Physicians include the statement "Women who have coronary heart disease are likely to benefit from hormone therapy". What evidence support this recommendation? More than 30 observation studies have examined the effect of estrogen replacement therapy on cardiovascular event and all cause mortality. In addition there have been 13 case controlled studies. The majority showed lower morbidity and mortality from coronary heart disease among users of postmenopausal estrogens than among non-users. Recently, 2 meta-analyses estimated the reduction in coronary heart disease associated with estrogen use to be in the range of 35 to 44%, respectively. All of these observational studies share a fatal flaw: Women who take estrogens are different from women who do not. Some differences have been measured, others have not. Women who take estrogens are on average better educated, healthier, have higher incomes and have better access to health care. These difference rather than the estrogens may account for much of the lower risk of heart disease. At this time we cannot tell from these observational studies what the real benefit of estrogens on coronary heart disease might be. Estrogen replacement therapy is not without risk. Estrogens increase the risk of endometrial carcinoma approximately 6-fold, an effect that is eliminated by the addition of progestins. Controversy continues over whether estrogen replacement increases the risk of breast cancer. A number of prospective randomized studies are now under way that will establish whether estrogen replacement therapy definitely reduces the risk of cardiovascular disease in women with and without coronary lesions and whether it increases the risk of breast cancer. Until the results of these trials are available claims on the definite usefulness of hormone supplementation to prevent coronary heart disease in postmenopausal women remain premature. In the light of the probable usefulness estrogen replacement therapy for the prevention of cardiovascular events should be recommended for women with increased risk for or definitively proven coronary heart disease.
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PMID:[Estrogens for prevention of coronary heart disease?]. 930 98

Estrogen is a key regulatory hormone, which in addition to its role in reproduction, affects a number of physiological systems, including the skeleton and cardiovascular system. The important role of estrogen in various tissues is perhaps most evident in postmenopausal women who, in addition to menopausal symptoms, experience increases in osteoporosis and coronary heart disease as their estrogen levels decline. Estrogen replacement, while effective against osteoporosis and heart disease, produces a number of side effects associated with the breast and uterus which limits compliance. Selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, produce beneficial estrogen-like effects on bone and lipid metabolism, while antagonizing estrogen in reproductive tissue. SERMs can be distinguished from each other in reproductive tissue, particularly the uterus, by their activity profile. For example, while triphenylethylenes like tamoxifen behave as partial agonists, raloxifene (a benzothiophene) behaves as a complete antagonist in the uterus. The SERM profile is distinct from that of full estrogens (ie. 17beta-estradiol or 17alpha-dihydroequilenin) which behave as estrogen agonists in all tissues and pure estrogen antagonists (i.e. ICI-164,384) which exhibit only an estrogen antagonist profile in a battery of tissue types. The precise mechanism by which SERMs produce this tissue-selective pharmacology remains a question. It is clear, however, that for raloxifene, both the estrogen agonist effects on bone and cholesterol metabolism as well as the estrogen antagonist effects in uterine and mammary tissue involve high affinity interaction with the estrogen receptor. The estrogen antagonist activity is mediated via classical pharmacological competition for estrogen receptor binding. The estrogen agonist activity, in bone for example, appears to involve novel post-receptor pathways and non-classical estrogen response element(s) which are activated by SERMs. These novel response elements may represent natural pathways which respond to estrogen metabolites in vivo.
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PMID:Selective estrogen receptor modulators: an alternative to hormone replacement therapy. 942 Dec 6

Estrogen replacement is often advised for postmenopausal women to prevent menopausal symptoms, osteoporosis and heart disease. However, little information is available concerning the half-life of estradiol (E2) in postmenopausal women. This study was designed to determine the half-life and metabolism of transdermal E2. A prospective clinical study of 8 healthy postmenopausal women was performed in the Clinical Research Center of the Brigham and Women's Hospital. A transdermal E2 patch 0.10 mg was placed on the abdominal wall. Thirteen hours later, after an overnight fast, the E2 patch was removed and frequent blood sampling was performed over 6 h. Serum samples were assayed for E2, estrone (E1) and estrone sulfate (E1S). Serum samples were taken before E2 patch placement, for 30 min before patch removal, and for 6 h after patch removal. The basal E2 level of women prior to use of transdermal E2 was 19 +/- 2 pg/ml (mean +/- SE). Thirteen hours after transdermal E2 placement, steady state levels had been reached, with a mean E2 of 112 +/- 6 pg/ml. The mean half-life of E2 after removal of transdermal E2 was 161 min (range 107-221 min). There was a direct relationship between the subjects' weight and the half-life of E2 (r = 0.79, p = 0.02). Mean basal E1 levels were 23 +/- 5 pg/ml and mean E1 steady-state levels after E2 patch placement were 39 +/- 0.6 pg/ml. E1S levels rose from mean basal levels of 1.5 +/- 0.3 ng/ml to mean steady-state levels of 3.1 +/- 0.1 ng/ml after placement of the E2 patch. The apparent half-life of E2 after discontinuing a transdermal E2 patch is 2.7 h or 161 min.
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PMID:Half-life of estradiol in postmenopausal women. 947 64

Cardiovascular disease is the leading cause of death among older American women. Estrogen replacement therapy (ERT) appears to reduce the risk of heart disease. For nearly five decades, the Type A behavior pattern (TABP) has been implicated in the cardiac morbidity and mortality of both men and women, but no studies have examined the use of replacement estrogen or whether its association with heart disease risk factors is different in Type A versus Type B women. We examined the effects of ERT and TABP on heart disease risk factors in a large population-based sample. Subjects were 1070 postmenopausal women, aged 50-89 years, who had been participants in the Rancho Bernardo Study. At a clinic visit made during 1984-1987, TABP was assessed with the Bortner Rating Scale, and heart disease risk factors (total cholesterol, high-density and low-density lipoprotein (HDL and LDL), triglycerides, fasting and postchallenge insulin and glucose, and blood pressure) were measured. Based on a median split (median = 154.0) of scores on the Bortner Rating Scale, 52% of these women were classified as Type A. Type A women were significantly younger than Rating women (mean = 68.4 versus 71.0 years, respectively). After adjustment for age, significantly more Type A than Type B women were on ERT (35% versus 24.7%, p = 0.001). Analyses stratified by TABP indicated that within the Type A group, current users of ERT had higher levels of HDL cholesterol (p) = 0.001) and lower levels of LDL cholesterol (p < 0.01), fasting plasma glucose (p < 0.001), and fasting insulin (p < 0.01). Among Type B women, current users of ERT had higher levels of HDL cholesterol (p = 0.07) and triglycerides (p < 0.01), lower levels of LDL cholesterol (p < 0.01), and lower systolic blood pressure (p < 0.05) but no significant differences in either fasting or postchallenge levels of either plasma glucose or serum insulin (each p < 0.01). Results of this study suggest that ERT may be associated with significant differences in the heart disease risk factor profile in Type A versus Type B women, and these differences may favor Type A women.
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PMID:Type A behavior pattern, heart disease risk factors, and estrogen replacement therapy in postmenopausal women: the Rancho Bernardo Study. 951 Nov 32

The Heart and Estrogen/progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease (CHD) events in women. The participants are postmenopausal women with a uterus and with CHD as evidenced by prior myocardial infarction, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or other mechanical revascularization or at least 50% occlusion of a major coronary artery. Between February 1993 and September 1994, 20 HERS centers recruited and randomized 2763 women. Participants ranged in age from 44 to 79 years, with a mean age of 66.7 (SD 6.7) years. Most participants were white (89%), married (57%), and had completed high school or some college (80%). As expected, the prevalence of coronary risk factors was high: 62% were past or current smokers, 59% had hypertension, 90% had serum LDL-cholesterol of 100 mg/dL or higher, and 23% had diabetes. Each woman was randomly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo. Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events (CHD death and nonfatal myocardial infarction). We will also assess other major CHD endpoints, including revascularization and hospitalization for unstable angina. The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo. The trial was designed to have power greater than 90% to detect a 35% reduction in the incidence of CHD events, assuming a 50% lag in effect for 2 years and a 5% annual event rate in the placebo group. The design, analysis, and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California, San Francisco. HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events.
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PMID:Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics. 968 9

Cardiovascular disease related to hyperlipidemia is a significant cause of morbidity and mortality in the United States. The benefit of lowering lipid levels in patients with and without cardiovascular disease has been demonstrated in numerous clinical trials. The results of these trials prompted the National Heart, Blood, and Lung Institute to form the Nation Cholesterol Education Panel (NCEP). This panel developed guidelines for identifying and treating lipid disorders. Before starting antilipemic therapy, patients should be evaluated for secondary causes of hyperlipidemia, including disease states and medications. Risk factors for cardiovascular disease should be identified and used to determine the patient's goal low-density lipoprotein level. Regardless of the drug therapy used, the cornerstone treatment for hyperlipidemia is dietary changes. The NCEP recommendation for dietary modification follows a two-step plan to reduce intake of cholesterol and dietary fats. Other nonpharmacologic treatments for hyperlipidemia include exercise, weight reduction for obese patients, reduction of excessive alcohol use, and smoking cessation . Drug therapy should be considered in patients who do not respond to an adequate trial of dietary modifications and lifestyle changes. The principal lipid-lowering agents currently used are the bile acid sequestrants, nicotinic acid, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, and fibric acid derivatives. Estrogen, fish oil, and alcohol also can decrease the risk of developing heart disease. In pharmacoeconomic studies, lipid-lowering drug therapy has been shown to decrease the number of procedures, hospitalizations, and other medical interventions required by patients with cardiovascular disease.
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PMID:Identifying and managing patients with hyperlipidemia. 1017 Mar 3


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