Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concensus conclusions reached at a concensus development conference on Estrogen Use and Postmenopausal Women in September 1979 are based on 3 position papers prepared for the conference, the response of the panel, and the general discussion by the audience, followed by the panel and other conference participants. The evidence for the efficacy of estrogens in treating specific conditions associated with menopause was reviewed 1st. It was accepted that estrogens are more effective than placebo in decreasing the frequency and severity of vasomotor symptoms. Estrogens are effective in overcoming the atrophy of the vaginal epithelium and the associated symptoms. Present evidence does not justify the use of estrogens to treat primary psychological problems. The validity of 3 randomized trials indicating that exogenous estrogens can retard bone loss if given around the time of menopause was acknowledged. There is no convincing evidence that estrogens in customary doses increase the risk of thromboembolic phenomena, stroke, or heart disease in women who have undergone natural menopause. Evidence was also reviewed concerning adverse effects associated with post-menopausal estrogen use. In the absence of exogenous estrogens, the incidence of endometrial cancer is about 1/1000 postmenopausal women per year. This rate increases severalfold beginning after about 2-4 years of use of 0.625 or 1.25 mg of conjugated estrogens daily. Cystic hyperplasia of the endometrium, regarded as a premalignant condition, has been associated with unopposed estrogen, whether endogenous or exogenous.
 ...
PMID:Estrogen use and postmenopausal women: a National Institutes of Health Consensus Development Conference. 4 37

The evidence that estrogen protects against coronary heart disease is biologically plausible, consistent, and strong. These benefits have not been established by a randomized trial, however, so that the degree of protection against heart disease might have been overestimated because estrogen users tend to be healthier than nonusers. A randomized trial to determine whether estrogen alone or in combination with progestin protects against coronary heart disease should be given a high priority. Progestins generally attenuate the effects of estrogen on the concentrations of HDLC. It is not known whether this effect also limits the beneficial effects of estrogen on the risk of coronary heart disease. Recent studies suggest that estrogen may protect against coronary heart disease in other ways besides favorably altering serum concentrations of lipoproteins and that progestins might not have adverse effects on the risk of heart disease. Currently, theoretical concerns that progestins might be harmful seem outweighed by the evidence that they protect against endometrial cancer in women who have a uterus. For these women, some may find the side effects of progestins to be so bothersome that they prefer to take estrogen alone. This approach is reasonable so long as the patient has periodic endometrial biopsies for early detection of pre-malignant or malignant endometrial changes. Women without a uterus should take estrogen alone. Women who take long-term estrogen therapy appear to have about a 30% greater chance of developing breast cancer. On the other hand, breast cancer that develops while taking estrogen therapy might have a slightly better prognosis. Quantitative comparisons of fatal conditions suggest that the benefits of long-term therapy outweigh the risks. But these comparisons assume that all causes of deaths are equally important and do not adequately take account of other psychologic and physical effects of hormone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Evaluating the benefits and risks of postmenopausal hormone therapy. 175 Apr 10

Serum sex hormones may be related to the risk of several diseases in postmenopausal women including osteoporosis, heart disease, and breast and endometrial cancer. For assessment of the relation of sex hormones to disease, the measurements should be reliable, valid, and practical. In this paper, the authors evaluated the short-term (4-week) and long-term (2-year) reliability of serum sex hormones and interrelations among serum sex hormones in white postmenopausal women recruited in Pittsburgh, Pennsylvania, 1981-1986. For comparison, the authors simultaneously evaluated the short- and long-term reliability of other commonly measured risk factors, i.e., lipids, lipoproteins, and blood pressure. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by extraction, column chromatography, and radioimmunoassay. Reliability was estimated by calculating the intraclass correlation coefficients (R) and their 95% confidence interval. About 50% of the estradiol levels were below the sensitivity of the assay and, therefore, these results should be interpreted with some caution. The intraclass correlation coefficient for testosterone was 0.92 (95% confidence interval 1.0-0.82), suggesting that a single measure may be reliable in characterizing women for epidemiologic research. Over 4 weeks, estrone could be measured more reliably (R = 0.72) than over 2 years (R = 0.56), but the variability over the long term was similar to that observed for other biologic variables, suggesting that, in situations where the relation between estrone and disease is fairly substantial, a single measure may be used. For estradiol and androstenedione, the intraclass correlations were small, indicating poor reproducibility and the need for more measurements. Estrone concentrations were 11 pg/ml or 46% higher in women with measurable estradiol. Estrone was also positively related to androstenedione concentrations (r = 0.33, p less than 0.001). Concentrations of estradiol are extremely low in postmenopausal women, and accordingly, there is a greater possibility of laboratory error. Since the data suggest that estrone levels can be more reliably measured and are, in fact, related to estradiol levels, it is possible that estrone levels may be used to indicate the total estrogen status of postmenopausal women.
 ...
PMID:Reliability and interrelations among serum sex hormones in postmenopausal women. 198 98

In order to achieve the long-term benefits from hormone replacement therapy of a markedly reduced incidence of heart disease and osteoporosis, a high degree of compliance is essential. In an effort to obtain high compliance, it was decided to introduce a cyclic therapy of 6 months duration using conjugated oestrogens supported by a 10-day course of progestogens. A total of 85 patients were treated prospectively. Compliance was assessed by the number of patients continuing treatment, and endometrial response was assessed by office biopsy and cytological or histological examination. Five patients withdrew, giving an overall compliance rate of 94%. Two have subsequently resumed therapy, thus 98% of those enrolled are currently receiving hormone replacement therapy. No cases of endometrial carcinoma were detected during the trial period of 4 years. Two cases of mild atypical endometrial hyperplasia were detected but both were mild and reverted to secretory or inactive endometrium following progestogen therapy. This regimen provides a viable alternative for those women who are troubled by progestogenic side-effects and monthly withdrawal bleeding.
 ...
PMID:An alternative regimen of hormone replacement therapy to improve patient compliance. 256 74

The risks and benefits of the newer oral contraceptives are evaluated, considering cancer, teratogenicity, drug interactions, cardiovascular risks, and carbohydrate metabolism. Oral contraceptives confer the lowest mortality risk of all contraceptives, except sexual abstinence, in all women under 30 and in nonsmokers through age 40 in developed countries. In less developed countries where maternal mortality can be as high as 5-10%, the risks of even nonmedically supervised oral contraceptives are dwarfed. The pill protects against ovarian cancer even after the pill is discontinued because it suppresses ovulation, and endometrial cancer because it blocks estrogen receptors. The relationship of oral contraception to breast cancer is still in dispute, but no good evidence exists for increased risk, especially with new low- dose pills. There may be a slightly increased risk of cervical cancer, although it is difficult to separate out other risk factors co-existing in pill users, such as earlier sexarche, more partners and more frequent screening. The incidence of pelvic inflammatory disease, functional ovarian cysts and ectopic pregnancy is reduced by pills. There is only 1 report of increased incidence of congenital heart disease in infants whose mothers took pills during pregnancy. Drug interactions are common, and must be managed by the physician. Among currently popular pills, only the norgestrel and levonorgestrel-containing multiphasic pills are said to decrease HDL2 and impair glucose tolerance, because they are androgenic enough to overcome the low dose of estrogen.
 ...
PMID:Oral contraceptives: a reassessment. 267 44

Early age at natural menopause or bilateral ovariectomy substantially reduce a woman's lifetime risk of breast cancer. Reversible 'bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising hormone releasing hormone (LHRH) agonists (LHRHAs). The harmful effects of such medical reversible bilateral ovariectomy, in particular the increased risks of coronary heart disease and osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such bilateral ovariectomy on breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective contraceptive, decrease her lifetime risk of breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of ovarian cancer by two-thirds. This regimen should leave endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of heart disease. The addition of a 'low-dose' progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards breast cancer. A satisfactory compromise may be to add a low-dose progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and endometrial cancer.
 ...
PMID:LHRH agonists and the prevention of breast and ovarian cancer. 267 44

The goal of contemporary hormone replacement is to minimize net predictable lifetime risk; success therefore depends upon quantitative assessments of the net quality of life, of net morbidity and of net mortality. Estrogens ameliorate menopausal symptoms, maintain bone integrity, and produce endometrial cancer; these facts and their quantitative aspects can be stimulated. Other links are gradually becoming clear: estrogens increase biliary disease, but prevent heart disease, and, it now seems, stroke. Conventional wisdom to the contrary notwithstanding, a critical review suggests that breast cancer is probably increased in frequency by long-term estrogen use; the increase is modest as a risk factor but because breast cancer is a common disease, it is substantial in absolute terms. The addition of progestin seems attractive as a method of opposing undesirable estrogenic effects on the endometrium. In fact, there is reason for concern about the effect of an added progestin upon the risks from breast cancer, heart disease, and stroke; even the magnitude of the expected reduction in endometrial cancer may not be great when the hormone is administered sequentially. Using a simple deterministic model of post-menopausal life with hormone replacement, we have inserted available estimates of the regimen-specific relative risk for each outcome, and translated each net impact into common denominators of morbidity and mortality. While estrogens probably increase net morbidity, as measured by either the number of hospitalizations to be anticipated or by the more arbitrary measure of expected days of disability, these negative changes are mostly due to gallbladder disease and endometrial cancer, both largely treatable conditions. Largely because of protection against heart disease, estrogen replacement in modest dose is likely to reduce substantially the number of deaths to be expected in women treated through age 75 and even into more advanced age. Hormone replacement which includes systemic progestin supplementation has not been empirically tested; it may be beneficial, but it is at least as likely to be harmful. Either a modest increment in the number of additional breast cancers produced by estrogens, a modest reduction in the number of cardiac events prevented by estrogens, or a simultaneous minor shift in the same direction for each condition, would have the effect of shifting the net reduction in cumulative deaths into an increase in the number of deaths as a result of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Risks and benefits of long-term treatment with estrogens. 269 47

Current research on lipid alterations and the risk of ischemic cardiopathy is reviewed, and the relationship of such cardiopathy to exogenous hormonal treatment is examined. Most large epidemiological and intervention studies have focused on men. Men and women share some risk factors, including high serum cholesterol levels, adverse lipoprotein profile, smoking, hypertension, diabetes, obesity, advanced age, and according to some studies sedentary life style. Additional factors that may affect women more than men are elevated serum triglyceride levels, natural or surgical menopause, use of oral contraceptives (OCs), and possibly hormonal substitution therapy. Studies have revealed a characteristic female profile of lipids and lipoproteins that follows a predictable course with age and menopause. Average total cholesterol and LDL cholesterol are higher in men than in premenopausal women, but women's levels rise after menopause until they eventually exceed those of men. According to epidemiological study and clinical trials over the past 2 decades, the principal determinants of serum lipid levels and hyperlipidemia are similar for both sexes and include diet, smoking, physical exercise and other habits, and genetic factors. Lipid levels in women are also affected by endogenous estrogens, high-dose OCs, estrogen replacement therapy, and menopause. Several studies have shown that high serum concentrations of total and LDL cholesterol and relatively low levels of HDL cholesterol are correlated with development of atherosclerotic lesions and increased cardiovascular risk in men, and that lowering cholesterol reduces the risk. Thus far there are no conclusive studies demonstrating the benefits of reduced cholesterol levels for women, but studies that included women along with men suggested that they share the benefits. Low levels of HDL cholesterol and elevated serum triglyceride levels appear to be important predictors of ischemic cardiopathy in women. The coronary risk in former OC users does not appear to be higher than that of women who never used OCs. It is likely that the lower-dosed formulations now in use will mitigate the risk. The adverse effect of OCs on lipid levels appears to be related to the androgenicity of the progestin. Most of the progestins used in combined pills are related to the 19-nortestosterone group which tends to decrease HDL level and increase LDL and triglyceride levels. Many studies have demonstrated that postmenopausal use of estrogens alone result in a decrease in LDL and an increase in HDL levels. Most but not all studies have shown that hormonal substitution reduces risks of coronary disease. But the longterm effects of estrogen/progestin use, now recommended to avoid increased risk of endometrial cancer, are not known.
 ...
PMID:[Women and ischemic cardiopathy]. 269 94

Progestogens should be added to estrogen replacement therapy, not only to prevent endometrial cancer in women with a uterus, but also to reduce the risk of breast cancer in some women. Smoking should be discouraged to reduce the risk for both lung cancer and heart disease. Recommendations should be made to increase fiber intake to lessen the risk for carcinoma of the colon. Reducing fat intake also decreases risk for colon cancer, as well as carcinoma of the breast. Postmenopausal bleeding must be investigated for early diagnosis of endometrial cancer and, when endometrial hyperplasia is the finding, it should be treated with progestogens to prevent adenocarcinoma. The progestogen challenge test is recommended for all women with a uterus, and if bleeding occurs, the progestogen should be continued for 13 days each month. Use of mammograms and other diagnostic modalities should be increased to make the earliest possible diagnosis of breast cancer.
 ...
PMID:Cancer in the older woman: diagnosis and prevention. 304 28

An estrogen-progestogen regimen of hormone replacement therapy has become widely used in recent years, primarily as a means to protect the endometrium from the carcinogenic effects of unopposed estrogen therapy (ERT). In this article, we evaluate the probable effects of this regimen on mortality from endometrial cancer as well as mortality from other chronic diseases. We conclude from this analysis that ERT is to be preferred to combination therapy for postmenopausal women without a uterus, primarily because it is predicted that ERT confers a significantly greater benefit on heart disease risk. In women with a uterus, if progestogens are to be prescribed, they should be given in the lowest possible dose needed to achieve the desired histologic changes in the endometrium, since the predicted loss in heart disease benefit from adding the progestogen is substantial.
 ...
PMID:Re-evaluating the role of progestogen therapy after the menopause. 336 Jan 88


1 2 3 4 Next >>