Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drospirenone (DRSP) is a novel progestogen derived from 170alpha-spirolactone. Its pharmacodynamic profile is closer to progesterone than any other currently available progestogen. DRSP has progestational, antialdosterone and antiandrogenic properties, but is devoid of any estrogenic, androgenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activities. The affinity of DRSP for the mineralocorticoid receptor makes it an antagonist of aldosterone, which is not only important in the renin-angiotensin-aldosterone system (RAAS), but also acts directly on the cardiovascular system. DRSP (1, 2 or 3 mg) in combination with 1 mg 17beta-estradiol (E2) is being developed by Schering AG as a continuous combined product for hormone replacement therapy (HRT). Phase II/III trials of E2/DRSP combinations have demonstrated clinical efficacy for the treatment of hot flushes, as well as improvement of bone density in the hip. Within 1 year of treatment with E2/DRSP, more than 80% of recipients regained amenorrhea. E2/DRSP at all three doses of DRSP is associated with a highly favorable safety profile, with excellent endometrial protection after 1 and 2 years (no cases of hyperplasia or cancer), favorable lipid profiles, with no evidence of attenuation of the beneficial effects on lipids of E2, probably due to DRSP's lack of androgenicity. Recipients of E2/DRSP combinations showed a small decrease in body weight, probably due to DRSP's antialdosterone properties. Adverse events with E2/DRSP did not differ significantly from those observed with standard HRT preparations. Phase III studies with E2/DRSP show that DRSP does not antagonize the well-documented reductions of blood pressure associated with E2; rather, small DRSP dose-related reductions in systolic and diastolic blood pressures were observed, which should be beneficial for recipients, especially those who are mildly hypertensive. These effects on blood pressure are probably due to DRSP displaying aldosterone receptor antagonism, a property which, in other settings, has been shown to convey benefits in terms of cardiovascular disease. Further studies of the cardiovascular effects of E2/DRSP combinations are anticipated.
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PMID:Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties. 1501 48

At least 20 million postmenopausal women worldwide now use some form of hormone replacement therapy. This figure is increasing because the resistance of the medical community to these therapies is diminishing and because of increasing acknowledgement of the benefits of such therapies on the cardiovascular system. This is a remarkable development for a medication originally used to relieve menopausal symptoms such as hot flushes and to prevent bone loss. Although several mechanisms are now accepted to be involved in this protection from cardiovascular disease, changes in plasma lipoproteins remain a major area of research interest. The main issue in this field, whether the addition of a progestogen to postmenopausal oestrogen ('combined therapy') will diminish the benefits on the cardiovascular system, remains unresolved, but combined therapies have now been formulated that minimize the potentially detrimental effects of progestogens on plasma lipoproteins. Recent findings of interest include the effects of these therapies on plasma lipoprotein (a) concentration and on LDL particle size. Studies of the mechanisms behind such changes are needed.
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PMID:Post-menopausal hormone replacement therapy, coronary heart disease and plasma lipoproteins. 1555 31

Women make up 55% of the total world population. This percentage is set to steadily increase over the next three decades. Europe also has the highest proportion of older women in the world. In fact, there are now approximately 3 women for every 2 men over 65. All of this data confirms the importance of prevention. An ideal approach for the female post-menopausal population would be treatment of any condition that can improve physical, mental and social well-being. Nevertheless, it is understood that the efficacy and cost/benefits of every screening programme need to be analysed. One of the largest and most neglected groups that could benefit from prevention consists of women without hot flushes (asymptomatic women), but with risk factors. The strategic measures are information, research and development of programmes. The more practical approach would be to identify patients and therefore yield better results in terms of health status and improvement. Statistics show that the three main causes of mortality and disability in developed countries for post-menopausal women are cardiovascular disease (CVD), cancer and osteoporosis-associated fractures. There are agreed recommendations to include some preventive measures for these three disorders in clinical practice for health professionals, at least at the minimal level. Research into the role that other diseases play will allow strategies to be developed in order to enhance prevention. Disorders such as urinary incontinence, dyspareunia, visual and hearing impairment and cognitive dysfunction are seen in significant percentages in post-menopausal women and may affect their quality of life. Health care professionals should bear in mind that many women may be reluctant to raise questions about some disorders spontaneously. Physicians should therefore search for patients with risk factors for these diseases. Prevention and treatment to avoid medical accidents will improve the quantity and quality of life.
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PMID:The importance of preventive health care in post-menopausal women. 1612 74

Alternative therapies are being used by postmenopausal women in attempts to treat all of the complaints and medical conditions of the menopause. One-fifth of those who take prescription drugs for these indications also take herbal remedies and/or high-dose vitamins, most often without disclosing the fact to the physician. Although studies of alternative therapies are short-term and rarely focused on safety--let alone efficacy--in the long-term, there are many studies spread over the large number of substances involved. More than 130 studies, including meta-analyses, are reviewed in this article under the headings of phytoestrogens, especially from soy; therapies for hot flushes; and preventives for cardiovascular disease, osteoporosis, and breast cancer. Special attention is given to the recently recognized daidzein metabolite equol, and for the sake of completeness there are reviews of the unconventional, but not botanical, treatments estriol, transdermal progesterone, and dehydroepiandrosterone. The total picture produced by conscientious review of the studies is bleak overall, but there seems to be good reason to pursue the possibilities inherent in soy protein with phytoestrogens in populations of women who endogenously produce equol.
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PMID:Alternative therapies for postmenopausal women. 1627 3

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.
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PMID:Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women. 1644 47

This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs.
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PMID:Dietary omega-3 fatty acids for women. 1725 47

Selective estrogen receptor modulators (SERMs) are compounds that display mixed estrogen agonist/antagonist activity. Currently, four SERMs are licensed for clinical use: tamoxifen, toremifene, clomifene and raloxifene. The STAR and RUTH trials have provided useful data about the potential role of SERMs in the primary prevention of breast cancer and cardiovascular disease in postmenopausal women. New-generation SERMs, such as bazedoxifene, arzoxifene, lasofoxifene and ospemifene, are currently being evaluated. The aim is to find a SERM that conserves the skeleton and prevents breast cancer without increasing the risk of endometrial cancer and venous thromboembolism, and without inducing hot flushes. Technological advances in the study of estrogen receptor activation will provide key information for drug development.
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PMID:The future of the new selective estrogen receptor modulators. 1744 65

Adjuvant endocrine therapy plays an important role in the management of hormone-receptor-positive early breast cancer, and has increased life expectancy for millions of women. Many patients receive adjuvant treatment for at least 5 years following tumor resection, hence good long-term safety is important for endocrine agents to gain widespread acceptance. Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile limits treatment duration to 5 years. Increased efficacy over tamoxifen and good tolerability have recently made the third-generation aromatase inhibitors (AIs) the first-choice agents for adjuvant endocrine therapy; however, it is currently not known whether AI therapy, like tamoxifen, will be limited to 5 years. Many side effects of endocrine therapy, such as hot flushes and mood disturbances, are related to estrogen deprivation and are common to tamoxifen and AIs, reflecting the mechanism of action of these drugs. In addition, tamoxifen has estrogenic effects that are beneficial in some tissues: tamoxifen lowers serum cholesterol levels and protects against bone loss and cardiovascular disease, but is also associated with potentially life-threatening side effects, such as endometrial cancer and thromboembolic disease. As AIs lack estrogenic activity, they are not associated with these serious adverse events. Clinical trials comparing AIs with tamoxifen in the adjuvant setting have shown that AIs are well tolerated and are associated with a lower incidence of gynecological symptoms and hot flushes than tamoxifen. However, AIs are associated with musculoskeletal side effects, such as arthralgia, myalgia and bone loss, but these events are preventable or manageable. The effects of AIs on lipid metabolism and the cardiovascular system are still debatable, but placebo-controlled trials provide no evidence to suggest that AIs adversely affect these systems. Furthermore, the AIs allow women to maintain a good quality of life, comparable with women receiving tamoxifen or placebo, and are a cost-effective therapeutic option. Ongoing trials will provide more information regarding the long-term effects of AI therapy and will provide comparative data on the efficacy and safety of the different AIs, thereby helping to determine the optimal treatment strategy for these highly effective and well-tolerated drugs.
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PMID:Safety profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer. 1789 Feb 11

Third-generation aromatase inhibitors (AIs) are replacing tamoxifen as adjuvant therapy in postmenopausal women with hormone-sensitive breast cancer due to their superiority shown in several recent head-to-head trials. Healthy postmenopausal women normally experience age-related side effects, and in postmenopausal women with breast cancer, these symptoms may be exacerbated by adjuvant endocrine therapy. This review evaluates the current literature regarding bone health, lipid metabolism, cardiovascular disease, gynecologic health, and cognition in postmenopausal women receiving adjuvant AI therapy. The AIs -- anastrozole, exemestane, and letrozole -- are generally well tolerated: most adverse events are mild to moderate and common to menopause. Common short-term AI-associated toxicities are hot flushes, musculoskeletal complaints/arthralgia, and bone loss, all of which can be effectively managed. AIs may lack the cardioprotective and lipid-lowering effects of tamoxifen but, in contrast to tamoxifen, do not increase the risk of serious life-threatening thromboembolic or cerebrovascular events or endometrial cancer. Every patient should be individually assessed with respect to therapy risks and benefits. Lifestyle, comorbidities, and concomitant medications must be considered, and the importance of compliance to adjuvant therapy should be discussed before selecting a treatment regimen. The superior efficacy of adjuvant AI therapy will in most cases outweigh the risk of bothersome side effects that can be prevented or easily managed.
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PMID:Menopausal symptoms and adjuvant therapy-associated adverse events. 1831 Feb 77

Climacteric complaints are the main indication for hormone replacement therapy (HRT) in the clinical practice. Observational studies demonstrating a protective effect of HRT on cardiovascular disease (CVD) were conducted in early menopausal, young, symptomatic women. Vasomotor symptoms correlate with lower level of plasma antioxidant activity, an increased cardiovascular reactivity to stressful situations, elevated cholesterol, higher sympathetic nerve activity, impaired flow-mediated dilation, hypertension and a higher risk of aortic calcification. All the available findings indicate that hot flushes can be seen as a marker for underlying vascular changes among mid-life, otherwise healthy, climacteric women. Thus, young, healthy symptomatic postmenopausal women differ from those without vasomotor symptoms with regard to cardiovascular risk factors. Therefore, responses to HRT can change in terms of cardiovascular outcomes according to the baseline vasomotor complaints. This point may explain, at least in part, the negative/null effects of HRT on cardiovascular disease observed in the trials where HRT was given to largely asymptomatic, elderly women.
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PMID:Vasomotor symptoms and cardiovascular risk. 1981 Dec 38


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