Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Controversy still rages about whether hormone replacement therapy (HRT) confers cardiovascular benefit or harm. There is a wealth of biological evidence that estrogen has a beneficial effect, supporting a large body of epidemiological evidence demonstrating reduction in coronary events with HRT. A large randomized placebo-controlled clinical trial of preventive strategies for coronary heart disease (CHD) in postmenopausal women, the Women's Health Initiative (WHI), included HRT arms. The published preliminary findings of this trial showed a significant increase in coronary events, stroke, venous thromboembolism and breast cancer with estrogen-progestogen, leading to the conclusion that HRT was unsafe to use other than for short-term relief of menopausal symptoms. But subsequent publications of the more complete data from WHI have shown no significant increase in CHD, and a tendency to a reduction in those initiating HRT below age 60 years. This is important because other therapeutic strategies for the primary prevention of CHD, such as aspirin and statins, are not of proven benefit in women, in contrast to men. Subsequent WHI findings have not shown a clear increase in breast cancer, and any potential increase from HRT is similar to that seen with many lifestyle factors and other commonly used medications. The preliminary WHI results do not reflect accurately true benefits and risks, and HRT should remain a potential preventive treatment for CHD.
 ...
PMID:Hormone replacement therapy and cardiovascular disease revisited. 1972 78

Worldwide evidence on menopausal hormone therapy shows that it does not reduce coronary heart disease (CHD) risk and that it increases the risks of breast cancer, stroke, and venous thromboembolism. These risks are not offset by reductions in hip fracture risk. Consequently, the Food and Drug Administration and other drug regulatory authorities agree that hormone therapy should be used chiefly for short-term relief of menopausal symptoms. Continuing speculation relates to the "postmenopausal estrogen timing" hypothesis, which proposes that hormone therapy initiated soon after menopause will prevent CHD while therapy started later will have a null or adverse effect. The detailed analyses of Women's Health Initiative data reviewed here specifically address the timing hypothesis. For hormone therapy initiated soon after menopause versus therapy started later, the findings demonstrate 1) similar null or adverse effects on CHD risk; 2) similar adverse effects on the risks of stroke and venous thrombosis; and 3) possibly greater adverse effects on breast cancer risk. Therefore, Women's Health Initiative data do not support the hypothesis of favorable effects in women starting hormone therapy soon after menopause. Hence, the overall trial findings, including net harm for combined estrogen-progestin and the lack of a net benefit for estrogen-only therapy, also apply to women initiating hormone therapy soon after menopause.
 ...
PMID:Invited Commentary: Hormone therapy risks and benefits--The Women's Health Initiative findings and the postmenopausal estrogen timing hypothesis. 1946 79

Many women are now using herbal medicines to try to relieve menopausal symptoms such as hot flushes and night sweats, in light of recent evidence suggesting that hormone replacement therapy (HRT) may increase the likelihood of breast cancer, ovarian cancer, venous thromboembolism, heart attacks and stroke.1-6 For example, one survey has suggested that around 40% of women in the UK have used complementary and alternative treatments for their menopausal symptoms.7 Here we review the efficacy and safety of herbal medicines for the relief of such symptoms.
 ...
PMID:Herbal medicines for menopausal symptoms. 1912 28

A detailed review of the literature was performed in a bid to identify the presence of a common link between specific hormone interactions and the increasing prevalence of global disease. The synergistic action of unopposed oestrogen and leptin, compounded by increasing insulin, cortisol and xeno-oestrogen exposure directly initiate, promote and exacerbate obesity, type 2 diabetes, uterine overgrowth, prostatic enlargement, prostate cancer and breast cancer. Furthermore these hormones significantly contribute to the incidence and intensity of anxiety and depression, Alzheimer's disease, heart disease and stroke. This review, in collaboration with hundreds of evidence-based clinical researchers, correlates the significant interactions these hormones exert upon the upregulation of p450 aromatase, oestrogen, leptin and insulin receptor function; the normal status quo of their binding globulins; and how adduct formation alters DNA sequencing to ultimately produce an array of metabolic conditions ranging from menopausal symptoms and obesity to Alzheimer's disease and breast and prostate cancer. It reveals the way that poor diet, increased stress, unopposed endogenous oestrogens, exogenous oestrogens, pesticides, xeno-oestrogens and leptin are associated with increased aromatase activity, and how its products, increased endogenous oestrogen and lowered testosterone, are associated with obesity, type 2 diabetes, Alzheimer's disease and oestrogenic disease. This controversial break-through represents a paradigm shift in medical thinking, which can prevent the raging pandemic of diabetes, obesity and cancer currently sweeping the world, and as such, it will reshape health initiatives, reduce suffering, prevent waste of government expenditure and effectively transform preventative medicine and global health care for decades.
 ...
PMID:The role of oestrogen in the pathogenesis of obesity, type 2 diabetes, breast cancer and prostate disease. 2053 61

Hormone replacement therapy (HRT) for post-menopausal symptoms in diabetes is associated with increased risk of coronary heart disease and stroke. Therefore, there is a need for new HRT with no adverse effects on diabetic post-menopausal women. We developed peptides as potential estrogen mimetic compounds and now we evaluated the effects of the most efficacious peptide; hexapeptide estrogen-mimetic peptide 1 (EMP-1) (VSWFFE) in comparison to estrogen (E(2)) and peptides with weak activity A44 (KAWFFE) and A45 (KRAFFE) on modulation of cell proliferation of vascular smooth muscle cells (VSMC) growing in normal (ng) or high glucose (hg) concentrations. In ng EMP-1-like E(2) inhibited cell proliferation at high concentration, and stimulated at low concentration. EMP-1 did not affect E(2) stimulation of DNA, but inhibited E(2) inhibition of cell proliferation at high concentration. All effects by the combination of EMP-1 and E(2) were abolished at hg. A44-stimulated cell proliferation at all concentrations and A45 had no effect. When A44 was co-incubated with E(2) at both concentrations, DNA synthesis was stimulated, but abolished at hg. A45 abolished E(2) stimulation and inhibition of cell proliferation at both glucose concentrations. All peptides tested except A45-stimulated CK-specific activity at both glucose concentrations. In hg A44 stimulation of DNA was unaffected as well as its inhibition by EMP-1. EMP-1 and A44 similar to E(2)-stimulated MAPK activity in ng or hg, suggesting similar mechanism of action. The results presented here suggest that EMP-1 provided it acts similarly in vivo can replace E(2) for treatment of post-menopausal women in hyperglycemia due to diabetes.
 ...
PMID:The effects of peptides with estrogen-like activity on cell proliferation and energy metabolism in human derived vascular smooth muscle cells. 2056 10

Hot flushes and night sweats (HF/NS) are commonly experienced by mid-aged women during the menopause transition. They affect approximately 70% of women but are regarded as problematic for 15-20% largely due to physical discomfort, distress, social embarrassment, and sleep disturbance. There is a need for effective and acceptable nonmedical treatments for menopausal symptoms due to the declining use of hormone therapy (HT) following publication of the Women's Health Initiative and other prospective studies which associated HT use with increased risk of stroke and breast cancer. HF/NS are an example of a physiological process embedded within, and moderated by, psychological processes, as evidenced by discrepancies between subjective experiences and physiologically measured symptoms. We describe a cognitive model of menopausal hot flushes that can explain symptom perception, cognitive appraisal, and behavioral reactions to symptoms. Theoretically, the model draws on symptom perception theory, self-regulation theory, and cognitive behavioral theories. The model can be used to identify the variables to target in psychological interventions for HF/NS and to aid understanding of possible mediating factors. As part of Phase II intervention development, we describe a cognitive behavioral treatment which links the bio-psycho-social processes specified in the model to components of the intervention.
 ...
PMID:A cognitive model of menopausal hot flushes and night sweats. 2095 69

Tibolone is a synthetic steroid marketed for the treatment of menopausal symptoms. A cohort study of women with no history of breast cancer showed that tibolone was associated with an increased risk of breast cancer. In women with a history of breast cancer, a placebo-controlled trial showed a higher risk of breast cancer recurrence with tibolone. A placebo-controlled trial of half the standard dose of tibolone showed no increased risk of breast cancer but was interrupted due to an increased risk of stroke. In practice, it is better simply not to use tibolone.
 ...
PMID:Tibolone and breast cancer. 2135 81

In 2000, approximately 10 million women were receiving hormone replacement therapy (HRT) for alleviation of menopausal symptoms. A number of prior animal studies suggested that HRT may be neuroprotective and cardioprotective. Then, in 2003, reports from the Women's Health Initiative (WHI) indicated that long-term estrogen/progestin supplementation led to increased incidence of stroke. A second branch of the WHI in women with prior hysterectomy found an even stronger correlation between estrogen supplementation alone and stroke incidence. Follow-up analyses of the data, as well as data from other smaller clinical trials, have also demonstrated increased stroke severity in women receiving HRT or estrogen alone. This review examines the studies indicating that estrogen is neuroprotectant in animal models and explores potential reasons why this may not be true in postmenopausal women. Specifically, age-related differences in estrogen receptors and estrogenic actions in the brain are discussed, with the conclusion that animal models of disease must closely mimic human disease to produce clinically relevant results.
 ...
PMID:Potential age-dependent effects of estrogen on neural injury. 2164 73

Hormone replacement therapy (HRT) has been shown to increase bone density, reduce the risk of fracture and can successfully relieve menopausal symptoms. From a time when HRT was the major therapeutic option for the management of osteoporosis, women and their clinicians now have a range of treatments available. Following the publication of the Women's Health Initiative (WHI) and the Million Women Study highlighting potential side-effects, such as breast cancer, heart disease and stroke, many doctors and women are now reluctant to use HRT. The National Osteoporosis Society felt that the role of HRT in the management of osteoporosis needed to be clarified. Using the Charity's expert clinical and scientific advisers, and through public consultation with members and key stakeholders, a Position Statement has been published. We conclude that HRT has a role to play in the management of osteoporosis in postmenopausal women below the age of 60 years. The key recommendations of the Position Statement are presented in this paper.
 ...
PMID:National Osteoporosis Society's Position statement on hormone replacement therapy in the prevention and treatment of osteoporosis. 2169 2

Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased fracture risk. Several therapeutic agents are now available to treat postmenopausal osteoporosis and prevent fractures. Combined calcium and vitamin D supplementation reduce the relative risk of non-vertebral fractures by about 18%. Hormone replacement therapy (HRT) should not be prescribed for osteoporosis in women who do not experience menopausal symptoms. The marked benefits of raloxifene on the reduction in invasive breast cancer and vertebral fracture risk are partially counterbalanced by a lack of effect on non-vertebral fracture risk, and an increased risk of venous thromboembolism and stroke. All four bisphosphonates available in Belgium, except ibandronate, have been shown to reduce the risk of vertebral, non-vertebral and hip fractures in prospective, placebo-controlled trials. Globally, the incidence of vertebral fractures is reduced by 41%-70%, and the incidence of non-vertebral fractures by 25%-39%. The anti-fracture efficacy of weekly or monthly doses of oral bisphosphonates has not been directly shown but is assumed from bridging studies based on BMD changes. To date, the various bisphosphonates have not been studied in head-to-head comparative trials with fracture endpoints. There are potential concerns that long-term suppression of bone turnover associated with bisphosphonate treatment may eventually lead to adverse effects, especially atypical femoral fractures and osteonecrosis of the jaw, but these cases are extremely rare. Teri-paratide (recombinant human 1-34 PTH) administered by daily subcutaneous injections decreases by 65% the relative risk of new vertebral fractures in patients with severe osteoporosis. Pivotal trials with strontium ranelate have shown a 41% reduction in new vertebral fractures and a 16% reduction in non-vertebral fractures over 3 years. Denosumab is a fully human monoclonal antibody to RANK Ligand that is administered as a 60-mg subcutaneous injection every 6 months. In the pivotal phase III trial, there was a 68% reduction in the incidence of new vertebral fractures, whereas the incidence of non-vertebral fractures was reduced by 20%. Several new approaches are being explored, including antibodies to sclerostin, cathepsin K inhibitors, src kinase inhibitors, and drugs that act on calcium sensing receptors.
 ...
PMID:How to manage postmenopausal osteoporosis? 2233 9


<< Previous 1 2 3 4 5 6 Next >>