Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now well established that replacement therapy with estrogen is an effective tool to manage menopausal symptoms. There is also increasing evidence that hormone replacement therapy has beneficial effects on the long-term consequences of estrogen deficiency, such as osteoporosis and ischemic heart disease. However, breast cancer patients have been traditionally denied the beneficial effects of hormone replacement therapy (HRT) because of the belief that renewed hormonal exposure would accelerate the growth of occult breast cancer or facilitate breast carcinogenesis. Based on new data and reanalysis of old data, a reappraisal of this belief has recently been proposed. Reports on a small number of patients who did receive HRT with no apparent effect on their breast disease warrant large-scale prospective studies on this issue. Meanwhile, pharmacological and "natural" alternatives to hormonal treatment are also available for breast cancer patients.
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PMID:Management of menopause in women with breast cancer. 774 87

The reduction in estrogen production that occurs at menopause is associated with several long term sequelae. There is an accelerated decrease in bone mineral density leading to an increased risk of osteoporotic fracture. Furthermore, changes in plasma lipid profiles and other cardiovascular parameters increase the risk of cardiovascular and cerebrovascular pathology. These effects are additional to the menopausal symptoms experienced by many women. The effectiveness of estrogen-based hormone replacement therapy (HRT) is well established in preventing bone mineral loss and also in ameliorating menopausal symptoms, with the addition of progestogen maintaining or possibly enhancing the bone-conserving effects. However, prolonged therapy appears to be necessary to conserve bone mineral density and prevent osteoporotic fracture, particularly in women aged greater than or equal to 75 years, and compliance with long term therapy is likely to be poor. Estrogen favourably alters plasma lipid profiles, improves coronary blood flow and inhibits the central distribution of body fat. Effects on haemostatic mechanisms and coronary vasomotor response to acetylcholine have also been suggested as mechanisms for the beneficial effects of estrogen on ischaemic heart disease. The effects of concomitant progestogens on plasma lipids are variable, and may depend on the type, dosage regimen and duration of therapy. Pharmacoeconomic analyses of HRT have used a variety of risk assumptions. Relative risk rates of osteoporotic fracture and mortality from myocardial infarction are assumed to reduce to 0.5 after greater than 5 years' therapy. Long term HRT is associated with a relative risk of approximately 1.3 for breast cancer, whereas the relative risk of endometrial cancer is 4.0 to 8.0 in women with intact uteri receiving prolonged unopposed estrogen therapy. HRT that includes progestogens is assumed to incur no added risk of endometrial cancer, and this treatment is generally recommended for women with intact uteri. Data concerning the effect of HRT on quality of life are limited and utility values for hip fracture of 0.95 to 0.36 have been assigned, depending on assumptions of disability. Cost-benefit, cost-effectiveness and cost-utility studies evaluating HRT in the prevention of osteoporotic fracture have differed widely in methodology, making comparison of results difficult. HRT appears to be most economically useful in the prevention of fracture if used in women who have undergone hysterectomy, in women with high risk of osteoporotic fracture or ischaemic heart disease, and/or in women with menopausal symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone replacement therapy: II. A pharmacoeconomic appraisal of its role in the prevention of postmenopausal osteoporosis and ischaemic heart disease. 1014 66

The beneficial effect of hormone replacement treatment (HRT) on osteoporosis and menopausal symptoms has been well documented in randomised trials, but the impact of oestrogen-mediated metabolic changes on the risk of ischaemic heart disease (IHD) is still debated. Randomised studies have shown that HRT increases levels of high-density lipoprotein cholesterol while causing a reduction in the levels of low-density lipoprotein cholesterol, serum fibrinogen, plasminogen activator inhibitor and homocysteine. In addition, HRT increases insulin sensitivity in both normoglycaemic and diabetic women. Unlike oral contraceptives, HRT has not been associated with an increase in arterial blood pressure, whereas a small increase in the risk of breast cancer and of venous thromboembolism appears to occur with both treatments. Interestingly, some data suggest that oestrogen preparations may have different effects on lipids. For instance, the beneficial effect on cholesterol metabolism observed with oral conjugated oestrogen does not occur with transdermal oestradiol, suggesting that the first-pass effect through the portal circulation may be necessary to achieve the full metabolic effect of oestrogen treatment. Nevertheless, although a wealth of observational studies show that HRT is associated with a significant reduction in morbidity and mortality from IHD, the only randomised data available to date do not support these findings in postmenopausal women with established coronary artery disease.
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PMID:Hormone replacement therapy and ischaemic heart disease among postmenopausal women. 1035 70

Hormone replacement therapy has increased in use as a result of its well-established benefits as an effective tool against such consequences as osteoporosis and ischemic heart disease and in the management of menopausal symptoms. However, its possible negative impact on the survival of patients with a previous diagnosis of breast, uterine, or ovarian cancer remains controversial. The risk:benefit analysis of hormone replacement therapy in this setting warrants further investigation. In the meantime, patients should be counseled on the risks, benefits, and contraindications of hormone replacement therapy before embarking on its use.
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PMID:Hormone Replacement Therapy in the Gynecologic and Breast Cancer Patient. 1079 69

The major biologically active circulating estrogen in both males and females is estradiol (E(2)). Circulating E(2) is a product of the ovarian granulosa cell and the testicular Leydig cell. Its gonadal formation is dependent on A-ring aromatization of its immediate precursor, testosterone, by a particular isoform of the enzyme aromatase, which also catalyses the conversion of the much weaker androgen, androstenedione, to the weak estrogen, estrone. E(2) is also formed in non-gonadal tissues, such as adipose tissue, liver, muscle and brain. Only adipose tissue makes significant extra-gonadal contributions to circulating estrogen. Loss of ovarian function during reproductive life, as a result of loss of gonadotropin secretion (secondary hypogonadism) or as a result of premature ovarian failure (generally defined as cessation of ovarian function prior to age 40), results in loss of the majority of circulating E(2) and of luteal progesterone. Loss of ovarian function at the menopause likewise results in a 90% loss of circulating E(2). The consequences of loss of ovarian function during reproductive life may be severe. Symptoms include hot flushes, night sweats, vaginal dryness and dyspareunia, loss of libido, loss of bone mass with subsequent osteoporosis and abnormalities of cardiovascular function, including a substantial increase in the risk of ischemic heart disease. Various regimens of estrogen replacement have been employed, aiming to eliminate symptoms, restore well-being and avert the consequences of estrogen depletion. The commonly adopted form of replacement is with the low-dose oral contraceptive pill for reasons of convenience, cost, efficacy, general freedom from side effects and the psychological advantage that many of the patient's peer group are also "taking the pill". An often neglected aspect of hormone therapy in the reproductive age group is the therapeutic use of testosterone. The application of such principles to the postmenopausal period is more problematic, as there is a common perception that the menopause is a normal physiological occurrence and that it is therefore not physiological to offer hormone therapy at that time. The pragmatic approach is to recommend standard therapy with estrogen and progestogen for the management of menopausal symptoms and to recommend longer term hormone replacement in the light of the individual's needs and current data with regard to efficacy for protection from osteoporosis and cardiovascular disease.
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PMID:Physiological principles of endocrine replacement: estrogen. 1178 92