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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen, with or without a progestin, is effective for the treatment of menopausal symptoms. Larger doses of estrogen/progestin have been used than required for the amelioration of menopausal symptoms. Both positive and negative outcomes of hormone therapy are reported in postmenopausal women. The positive aspects have been those associated with a reduction in menopausal symptoms such as hot flashes, and improvement in vulvovaginal atrophy with maintenance of bone mineral density. The problems have included an increased risk of venous thrombosis and breast cancer. The anticipation is that as the dose of oral estrogen and progestins is lowered, the benefits can be maintained and the side effects reduced. Recent clinical trials have found that lower doses of estrogen and/or progestin reduce or improve menopausal symptoms and maintain bone mineral density. The impact of lower doses of hormones on heart disease, and venous thromboembolism and stroke remain to be determined in future studies.
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PMID:Lower doses of oral estrogen and progestogens as treatment for postmenopausal women. 1585 5

A distinctive feature of galanin expression is that it is extensively increased by neuronal injury, estrogens, Alzheimer's disease and during development. Since stroke is amongst the clinically most important causes of neuronal injury we studied the tissue concentrations of galanin in a rat stroke model and the possibility of modulating this effect with estrogen. Transient focal middle cerebral artery ischemia was induced in rats that 2 weeks earlier underwent ovariectomy and received 1.5mg 17beta-estradiol slow-release or placebo pellets. The concentrations of galanin and neuropeptide Y were measured after observation periods of 3, 7 and 14 days in extracts of punch biopsies from both the lesioned and the contra lateral control hemisphere. The galanin levels were not changed in any of the brain regions studied except in the hippocampus where they were lower in the ischemic hemisphere in both the estrogen- and placebo-treated animals compared to the corresponding contra lateral intact hemisphere (p=0.015). Estrogen treatment up-regulated galanin concentrations in both the ventral and dorsal hippocampus (p=0.003). The effects on the galanin concentrations were similar after all observation periods: 3, 7 and 14 days (p=0.144). No significant changes were observed in the concentration of neuropeptide Y in response to the lesions. The ischemic lesions were markedly larger in the estrogen-treated animals observed after 3 days compared to the corresponding control group. In the estrogen group the lesion was largest at bregma and the slice 2mm anterior to the bregma, 82% and 435% larger than in the control group (p<0.001). A similar, but much less pronounced (not statistically significant) difference was seen in the groups observed after 7 and 14 days. Earlier studies of lesions in the peripheral and central nervous systems have generally shown an up-regulation of galanin markers in response to but at a distance from the injury. Our results indicate that galanin is not involved in the response of the ischemic penumbra itself to stroke, whereas it may participate in the reactions of the neural stem-cell rich hippocampus to stroke.
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PMID:Estradiol increases brain lesions in the cortex and lateral striatum after transient occlusion of the middle cerebral artery in rats: no effect of ischemia on galanin in the stroke area but decreased levels in the hippocampus. 1591 33

Estrogen is a powerful neuroprotective agent in rodent models of ischemic stroke. However, in humans, estrogen treatment can increase risk of stroke. Health risks associated with hormone replacement have led many women to consider alternative therapies including high-soy diets or supplements containing soy isoflavones, which act as estrogen receptor ligands to selectively mimic some of estrogen's actions. We hypothesized that a high-soy diet would share the neuroprotective actions of estrogen in focal cerebral ischemia. Female Sprague-Dawley rats were ovariectomized and divided into three groups: isoflavone-free diet + placebo (IF-P), isoflavone-free diet + estradiol (IF-E), or high-soy diet + placebo (S-P). Two weeks after being placed on diets, rats underwent left permanent middle cerebral artery occlusion (MCAO). Reductions in ipsilateral cerebral blood flow were equivalent across groups ( approximately 50%). Twenty-four hours later neurological deficit was determined, and brains were collected for assay of cerebral infarct by TTC staining. In the IF-P rats MCAO produced a 50 +/- 4% cerebral infarct. Estrogen and high-soy diet both significantly reduced the size of the infarcts to 26 +/- 5% in IF-E rats and to 37 +/- 5% in S-P rats. Analysis at five rostro-caudal levels revealed that estrogen treatment was slightly more effective at reducing infarct size than high soy diet. Overall neurological deficit scores at 24 h correlated with infarct size; however, there were no statistically significant differences among the treatment groups. These data show that 2 wk of a high-soy diet is an effective prophylactic strategy for reducing stroke size in a rat model of focal cerebral ischemia.
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PMID:High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats. 1595 59

The Women's Health Initiative (WHI) hormone trials have been widely interpreted as demonstrating that combined menopausal hormone therapy (HT) fails to protect against-and may increase-cardiovascular disease (CVD), stroke, and dementia in menopausal women, regardless of whether initiated early in the menopause or later. This conclusion does not agree with results of large epidemiological studies showing protection by HT and by estrogen replacement alone (ET) against CVD and dementia. One possible reason for this inconsistency is that the epidemiologic data are confounded by "healthy user bias." Another possible explanation is that most women in the observational studies initiated ET or HT at or near the menopausal transition, at which point there is little or no arterial injury, whereas, in the WHI studies, older women, averaging approximately 12 years postmenopausal, many of whom would have had significant asymptomatic atherosclerosis, were treated. Substantial data demonstrate atheropreventive effects of estrogen before vascular damage occurs, whereas adverse effects of oral estrogen on thrombosis and inflammation may predominate once complex atheromas are present. Similarly, the excess of dementia observed in older WHI women treated with oral conjugated estrogen could be due to cerebral thromboses (multi-infarct dementia). Given the uncertain relevance of the WHI (and other published randomized clinical trials) to initiation of HT in perimenopausal women, and its subsequent continuation for atheroprevention, new trials will be needed to resolve whether early intervention with estrogen may prevent CVD and/or dementia. The Kronos Early Estrogen Prevention Study (KEEPS), which began in mid-2005, is a randomized, controlled multicenter trial of HT in recently menopausal women. It will examine surrogate end points as well as risk factors for atherosclerosis.
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PMID:Is the estrogen controversy over? Deconstructing the Women's Health Initiative study: a critical evaluation of the evidence. 1602 50

Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies.
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PMID:Combined postmenopausal hormone therapy and cardiovascular disease: toward resolving the discrepancy between observational studies and the Women's Health Initiative clinical trial. 1664 6

Large differences exist between women and men in the syndrome of heart failure (HF). In contrast to men, hypertension and diabetes represent the major risk factors for development of HF in women and hypertension is also the major cause of left ventricular hypertrophy and stroke. Left ventricular hypertrophy in women increases the risk for mortality to a higher degree than it does in men. The clinical course of HF is generally more benign and more frequently characterized by HF with preserved systolic function. Estrogen receptors are present in the human heart. Based on data from rodent models, they are believed to modulate hypertrophy and the progression of HF. Some of the signaling pathways have been described and involve phosphorylation of intracellular kinases and production of nitric oxide. Interestingly, estrogen receptors are upregulated in human hypertrophy and HF. The clinical course of HF in women is characterized by the more frequent occurrence of diastolic HF. Myocardial remodeling with age and, as a consequence, of mechanical load is different in both genders. Adherence to guidelines in the diagnosis and treatment of HF is less strict in women than in men, leading to undertreatment with inhibitors of the renin-angiotensin system. Women are generally underrepresented in clinical trials in HF and gender-specific analyses have been neglected in most older large survival trials. In some of the large survival studies angiotensin-converting enzyme inhibitors or beta-receptor blockers did not reach significant endpoints in women. However, meta-analyses show overall positive effects for these groups of substances. Angiotensin receptor blockers were effective in large studies including high percentages of women.
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PMID:Heart failure and its treatment in women. Role of hypertension, diabetes, and estrogen. 1613 38

Although previous studies demonstrated beneficial effects of estrogen on cardiovascular function, the Women's Health Initiative has reported an increased incidence of coronary heart disease and stroke in postmenopausal women taking hormone replacement therapy. The objective of the present study was to identify a molecular mechanism whereby estrogen, a vasodilatory hormone, could possibly increase the risk of cardiovascular disease. Isometric contractile force recordings were performed on endothelium-denuded porcine coronary arteries, whereas molecular and fluorescence studies identified estrogen signaling molecules in coronary smooth muscle. Estrogen (1-1,000 nM) relaxed arteries in an endothelium-independent fashion; however, when arteries were pretreated with agents to uncouple nitric oxide (NO) production from NO synthase (NOS), estrogen contracted coronary arteries with an EC(50) of 7.3 +/- 4 nM. Estrogen-induced contraction was attenuated by reducing superoxide (O(2)(-)). Estrogen-stimulated O(2)(-) production was detected in NOS-uncoupled coronary myocytes. Interestingly, only the type 1 neuronal NOS isoform (nNOS) was detected in myocytes, making this protein a likely target mediating both estrogen-induced relaxation and contraction of endothelium-denuded coronary arteries. Estrogen-induced contraction was completely inhibited by 1 muM nifedipine or 10 muM indomethacin, indicating involvement of dihydropyridine-sensitive calcium channels and contractile prostaglandins. We propose that a single molecular mechanism can mediate the dual and opposite effect of estrogen on coronary arteries: by stimulating type 1 nNOS in coronary arteries, estrogen produces either vasodilation via NO or vasoconstriction via O(2)(-).
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PMID:Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle. 1616 67

Estrogen's prothrombotic effects are of increasing concern, particularly in stroke risk and recovery. Using an ischemic rodent model, the authors sought to determine (a) if estrogen replacement increases postischemic platelet reactivity, (b) if changes in estrogen status alter intraplatelet endothelial nitric oxide synthase (eNOS) synthesis, and (c) if estrogen-mediated effects on platelets alter cerebral blood flow during reperfusion. Intact (I), ovariectomized (OVX), and OVX + 17 beta-estradiol (E50) rats were subjected to 30 min of forebrain ischemia and 60 min of reperfusion. Using the platelet activation marker P-selectin, postischemic platelet reactivity was quantified by flow cytometry. In a separate cohort (I, OVX, E50), the authors quantified platelet eNOS by Western blot. Another cohort (OVX, E50) was subjected to ischemia/reperfusion, and cerebral blood flow was determined using the iodoantipyrine technique. Collagen-stimulated platelet P-selectin expression was increased in the OVX rats at 60 min of reperfusion, and this effect was reversed by estrogen treatment. No differences in platelet eNOS expression were detected among groups. Cerebral blood flow at 60 min reperfusion was comparable between the OVX and the E50 rats. The authors conclude that during reper-fusion, estrogen deficiency increases postischemic platelet sensitivity to stimuli in estrogen-deficient rats. Estrogen treatment mitigates effects of estrogen loss on platelets, but this early effect is apparently not caused by intraplatelet eNOS depression. Neither estrogen deficiency nor estrogen treatment changes early postischemic regional brain blood flow. In this rodent global cerebral ischemic model, physiologic doses of estrogen are not deleterious to platelet reactivity and may initially reduce postischemic platelet reactivity.
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PMID:Effects of estrogen on platelet reactivity after transient forebrain ischemia in rats. 1626 75

The E65K polymorphism in the beta1-subunit of the large-conductance, Ca2+-dependent K+ (BK) channel, a key element in the control of arterial tone, has recently been associated with low prevalence of diastolic hypertension. We now report the modulatory effect of sex and age on the association of the E65K polymorphism with low prevalence of diastolic hypertension and the protective role of E65K polymorphism against cardiovascular disease. We analyzed the genotype frequency of the E65K polymorphism in 3924 participants selected randomly in two cross-sectional studies. A five-year follow-up of the cohort was performed to determine whether cardiovascular events had occurred since inclusion. Estrogen modulation of wild-type and mutant ion channel activity was assessed after heterologous expression and electrophysiological studies. Multivariate regression analyses showed that increasing age upmodulates the protective effect of the K allele against moderate-to-severe diastolic hypertension in the overall group of participants (odds ratio [OR], 0.35; P=0.006). The results remained significant when analyses were restricted to women (OR, 0.18; P=0.02) but not men (OR, 0.46; P=0.09). This effect was independent of the reported acute modulation of BK channels by estrogen. A five-year follow-up study also demonstrated a reduced age- and sex-adjusted hazard ratio of 0.11, 95% CI, 0.01 to 0.79 of K-carriers for "combined cardiovascular disease" (myocardial infarction and stroke) compared with EE homozygotes. Our study provides the first genetic evidence for the different impact of the BK channel in the control of human blood pressure in men and women, with particular relevance in aging women, and highlights the E65K polymorphism as one of the strongest genetic factors associated thus far to protection against myocardial infarction and stroke.
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PMID:Protective effect of the KCNMB1 E65K genetic polymorphism against diastolic hypertension in aging women and its relevance to cardiovascular risk. 1629 91

The cessation of ovarian estrogen production occurring around the time of menopause has the potential to influence central nervous system function, as well as a number of neurological disorders that affect women during midlife and old age, including memory loss and mild cognitive impairment, ischemic stroke, Parkinson's disease, and Alzheimer's disease. During midlife, there is observational evidence that episodic memory is not substantially affected by natural menopause or by use of estrogen-containing hormone therapy, but short-term clinical trial evidence suggests hormone therapy might benefit verbal memory after surgical menopause. Clinical trial data indicate that hormone therapy does not reduce, and may increase, stroke incidence. Parkinson's disease and Alzheimer's disease are the 2 most common neurodegenerative illnesses. Estrogen influences dopaminergic pathways within the central nervous system. However, available observational evidence is limited and inconclusive regarding any role of hormone therapy in influencing risk or symptoms of Parkinson's disease, a disorder of dopaminergic neurons. Finally, clinical trial data indicate that hormone therapy should not be initiated in the late postmenopause with the goal of improving memory, preventing cognitive decline, reducing dementia risk, or improving Alzheimer's disease symptoms. An important priority for clinical investigation is to determine whether hormone therapy used during the menopausal transition and early postmenopause has long-term effects on cognition or dementia risk. The critical window hypothesis as applied to Alzheimer's disease conjectures that effects of early hormone therapy might differ from those of hormone therapy initiated in the late postmenopause, but convincing evidence is yet to be obtained.
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PMID:Menopause and disorders of the central nervous system. 1630 63


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