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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several clinical studies suggest that estradiol acts as a potent growth and protective factor in the adult brain. Postmenopausal women experience permanent hypoestrogenicity and suffer from increased risk of brain injury associated with neurodegenerative diseases such as stroke and Alzheimer's disease. Estrogen replacement therapy appears to decrease the risk and severity of these neurodegenerative conditions. Studies using animal models have shown that estradiol exerts similar effects in rodents and can enhance cell survival and induce synaptic plasticity. Therefore, we undertook studies to assess whether estradiol treatment can decrease brain injury and cell death induced by an experimental model of ischemia and whether aging animals remain responsive to the protective effects of estradiol. We will review results from recent studies that demonstrate that 1) in young animals, estrogens exert profound protective effects against ischemic brain injury induced by cerebral artery occlusion and 2) the response of aging animals has been tested with varying results. We will discuss and compare our experimental findings that utilize a permanent cerebral artery occlusion model and physiological levels of estradiol replacement therapy in young and middle-aged rats with those of previous studies. These observations provide important insights into the potential protective actions of estrogen replacement therapy on age- and disease-related processes in the brain.
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PMID:Estradiol protects against ischemic brain injury in middle-aged rats. 1099 17

This review highlights recent evidence from clinical and basic science studies supporting a role for estrogen in neuroprotection. Accumulated clinical evidence suggests that estrogen exposure decreases the risk and delays the onset and progression of Alzheimer's disease and schizophrenia, and may also enhance recovery from traumatic neurological injury such as stroke. Recent basic science studies show that not only does exogenous estradiol decrease the response to various forms of insult, but the brain itself upregulates both estrogen synthesis and estrogen receptor expression at sites of injury. Thus, our view of the role of estrogen in neural function must be broadened to include not only its function in neuroendocrine regulation and reproductive behaviors, but also to include a direct protective role in response to degenerative disease or injury. Estrogen may play this protective role through several routes. Key among these are estrogen dependent alterations in cell survival, axonal sprouting, regenerative responses, enhanced synaptic transmission and enhanced neurogenesis. Some of the mechanisms underlying these effects are independent of the classically defined nuclear estrogen receptors and involve unidentified membrane receptors, direct modulation of neurotransmitter receptor function, or the known anti-oxidant activities of estrogen. Other neuroprotective effects of estrogen do depend on the classical nuclear estrogen receptor, through which estrogen alters expression of estrogen responsive genes that play a role in apoptosis, axonal regeneration, or general trophic support. Yet another possibility is that estrogen receptors in the membrane or cytoplasm alter phosphorylation cascades through direct interactions with protein kinases or that estrogen receptor signaling may converge with signaling by other trophic molecules to confer resistance to injury. Although there is clear evidence that estradiol exposure can be deleterious to some neuronal populations, the potential clinical benefits of estrogen treatment for enhancing cognitive function may outweigh the associated central and peripheral risks. Exciting and important avenues for future investigation into the protective effects of estrogen include the optimal ligand and doses that can be used clinically to confer benefit without undue risk, modulation of neurotrophin and neurotrophin receptor expression, interaction of estrogen with regulated cofactors and coactivators that couple estrogen receptors to basal transcriptional machinery, interactions of estrogen with other survival and regeneration promoting factors, potential estrogenic effects on neuronal replenishment, and modulation of phenotypic choices by neural stem cells.
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PMID:Neuroprotection by estradiol. 1104 Apr 17

All the hormonal events of the female life may modify the course of the migrainous disease. Their influence is slightly different on migraine with and without aura. Development of migraine at menarche and menstrually-related migraine attacks are principally observed in migraine without aura. Percutaneous estradiol is often effective for the prevention of pure menstrual migraine. Migraine usually improves during pregnancy; a worsening or a first development of attacks may nevertheless occur during this period, especially for migraine with aura. Oral contraception is not contraindicated in most migraine sufferers; it may worsen, improve or leave unchanged their disease. Migraine represents a risk factor of ischaemic stroke in young women; though a low one, some caution is necessary: tobacco should be forbidden, and the use of low-dose estrogen pills is recommended. Oral contraceptives should be interrupted in case of worsening of migraine, especially with aura. Estrogen replacement therapy is allowed after menopause in migraine sufferers; it may sometimes exacerbate migraine, which is in most cases controlled by therapeutic adjustment.
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PMID:[Female hormones and migraine]. 1107 47

In every year since 1984, cardiovascular disease has claimed the lives of more females than males. More than 450,000 women succumb to heart disease annually, and 250,000 die of coronary artery disease. Despite the proportions, most women believe they will die of breast cancer. The perception that heart disease is a man's disease and that women are more likely to die of breast cancer is alarming. Although women develop heart disease about 10 years later than men, they are likely to fare worse after a heart attack. The poorer outcomes are due, in part, to the failure to identify heart attack symptoms. Approximately 35% of heart attacks in women are believed to go unnoticed or unreported. However, because of increased age, women are more likely to have co-morbid diseases such as diabetes and hypertension. In women, not only is "tightness" or discomfort in the chest a warning sign, but in addition, nausea and dizziness are common indicators of myocardial ischemia. Other symptoms include breathlessness, perspiration, a sensation of fluttering in the heart, and fullness in the chest. In comparison to men, women are less likely to undergo tertiary care interventions such as cardiac catheterization, angioplasty, thrombolytic therapy, and bypass surgery; to participate in cardiac rehabilitation; and to return to work full-time after myocardial infarction. In the past, most research about treatments for heart disease focused on men, and gender differences have been ignored. Recent studies are enrolling enough women to test if there are differences between men and women in outcomes. One of the major areas of research relates to estrogen and hormonal replacement therapy to reduce the relative risk of heart attack and stroke. The Women's Health Initiative is a major NIH-sponsored trial that addresses the issue of primary prevention of cardiac disease by hormonal replacement therapy. The results will be available in 2004. The Heart Estrogen/Progestin Replacement Study (HERS), disappointingly, did not show a significant reduction of coronary events in women taking hormonal replacement therapy, nor did the Estrogen Replacement and Atherosclerosis (ERA) trial of 309 postmenopausal women who underwent coronary angiography. New insight into the role of vitamins, phytoestrogens and other natural sources, and selective estrogen receptor modulators may provide other options for management. Until then, modification of risk factors and healthy life style choices are recommended for reducing the risk of cardiac disease. In fact, the key to a healthy heart in the year 2000 appears closely tied to life style choices. Prevention of disease is the key, and current recommendations are simply to stop smoking, or do not start; treat and control blood pressure >140/90 mm Hg; manage elevated lipids by diet, exercise, and cholesterol-lowering medications (if necessary); treat diabetes; lose weight so that BMI is <25; walk for 20-30 minutes at least three times a week; and take an aspirin tablet daily.
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PMID:Heart disease in women. 1114 May 44

Estrogen replacement therapy in postmenopausal women ameliorates cognitive dysfunction and decreases the risk and/or severity of neurodegenerative conditions such as Alzheimer's disease and stroke. Furthermore, estradiol exerts neuroprotective effects in a variety of in vitro and in vivo models of brain injury. We have previously shown that physiological levels of estradiol attenuate ischemic brain injury in young female rats. However, neurodegenerative events occur more frequently in elderly women who are chronically hypoestrogenic. Therefore, we investigated whether aging rats remain responsive to the neuroprotective actions of estradiol. Young (3-4 months) and middle-aged (9-12 months) rats were ovariectomized and treated for 1 week with estradiol before middle cerebral artery occlusion (MCAO). Regional cerebral blood flow was monitored in some animals at the time of injury. Brains were collected 24 h after MCAO and infarct volume was analyzed. Our data demonstrate that in both young and aging rats, low and high physiological doses of estradiol decrease ischemic injury by almost 50%, compared with oil-treated controls. Additionally, our data suggest that estradiol acts in both age groups via blood flow-independent mechanisms, as basal and postinjury blood flow was equivalent between estradiol- and oil-treated young and aging rats. These data demonstrate that replacement with physiological levels of estradiol protects against stroke-related injury in young and aging female rats and strongly suggest that older animals remain responsive to the protective actions of estradiol.
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PMID:Neuroprotective effects of estradiol in middle-aged female rats. 1114 65

Estrogen has demonstrated great potential as a therapeutic agent in focal ischemic brain injury, as exogenous beta-estradiol has proven beneficial in a variety of focal stroke models. In contrast, the relatively few studies of estrogen's efficacy in transient forebrain ischemia have produced inconsistent results. The present study was therefore designed to clarify estrogen's neuroprotective potential in selective hippocampal neuronal injury resulting from four-vessel occlusion in the rat. Female Wistar rats (normal, ovariectomized, or ovariectomized and estradiol-treated) received 5 or 10 min of ischemia. No differences in hippocampal cell loss were found amongst the groups with 10 min of ischemia. Amongst the groups with 5 min of ischemia, the mildest injury was found in the ovariectomized animals, which lost only 32% of their CA1 pyramidal cells. In comparison, mean cell losses were 54% and 49%, respectively, in intact females and in ovariectomized animals with estradiol replacement. Linear regression analysis demonstrated a highly significant relationship between cell loss and plasma estradiol levels. The mechanism by which exogenous and endogenous estrogen exacerbated the injury is unclear, as estrogen has many neuroprotective effects. On the other hand, many other reported effects of estrogen in hippocampal area CA1 might confer increased sensitivity to ischemia, either by modulating the excitatory effects of glutamate or by modifying the inhibitory effects of GABA. Determining how to modulate the various competing effects of estrogen is of both theoretical and practical importance, as it is now clear that one cannot assume that estrogen administration will always improve outcome in cerebral ischemia.
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PMID:Deleterious effect of beta-estradiol in a rat model of transient forebrain ischemia. 1132 56

Estrogen and progesterone, long considered for their roles as primary hormones in reproductive and maternal behavior, are now being studied as neuroprotective and neuroregenerative agents in stroke and traumatic brain injuries. Collectively, the hormones reduce the consequences of the injury cascade by enhancing anti-oxidant mechanisms, reducing excitotoxicity (altering glutamate receptor activity, reducing immune inflammation, providing neurotrophic support, stimulating axonal remyelinization), and enhancing synaptogenesis and dendritic arborization. Estrogen seems more effective as a prophylactic treatment in females at risk for cardiac and ischemic brain injury, whereas progesterone appears to be more helpful in the post-injury treatment of both male and female subjects with acute traumatic brain damage. However, a recent clinical trial with estradiol replacement therapy in elderly women that have a history of cerebrovascular disease, showed that this hormone was unable to protect against reoccurrence of ischemia or to reduce the incidence of mortality compared to a placebo.
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PMID:Brain damage, sex hormones and recovery: a new role for progesterone and estrogen? 1141 Feb 69

Several studies have provided evidence to suggest that estrogen results in a significant reduction (approximately 50%) in the size of the ischemic zone in the middle cerebral artery occlusion (MCAO) model of stroke in a rat. The current study was done to demonstrate whether this estrogen-induced reduction in infarct size is associated with normalization of the autonomic dysfunction observed in an acute model of stroke in male rats. Experiments were done in anesthetized (thiobutabarbitol sodium; 100 mg/kg) male Sprague-Dawley rats instrumented to record baseline and reflex changes in cardiovascular and autonomic parameters. Estrogen was intravenously administered 30 min before, immediately before, or 30 min after MCAO. Estrogen administration resulted in a recovery of autonomic function and prevented the detrimental changes in autonomic tone observed following a stroke. In addition, infarct size was significantly increased in the presence of the estrogen antagonist ICI-182,780. These results suggest that both pre- or poststroke estrogen administration prevents or reverses acute stroke-induced autonomic dysfunction and that endogenous estrogen levels in males can contribute to this neuroprotection.
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PMID:Estrogen-induced recovery of autonomic function after middle cerebral artery occlusion in male rats. 1164 Nov 25

Besides their well-established actions on reproductive functions, estrogens exert a variety of actions on many regions of the nervous system that influence higher cognitive function, pain mechanisms, fine motor skills, mood, and susceptibility to seizures; they also appear to have neuroprotective actions in relation to stroke damage and Alzheimer's disease. Estrogen actions are now recognized to occur via two different intracellular estrogen receptors, ER-alpha and ER-beta, that reside in the cell nuclei of some nerve cells, as well as by some less well-characterized mechanisms. In the hippocampus, such nerve cells are sparse in number and yet appear to exert a powerful influence on synapse formation by neurons that do not have high levels of nuclear estrogen receptors. However, we also find nonnuclear estrogen receptors outside of the cell nuclei in dendrites, presynaptic terminals, and glial cells, where estrogen receptors may couple to second messenger systems to regulate a variety of cellular events and signal to the nuclear via transcriptional regulators such as CREB. Sex differences exist in many of the actions of estrogens in the brain, and the process of sexual differentiation appears to affect many brain regions outside of the traditional brain areas involved in reproductive functions. Finally, the aging brain is responsive to actions of estrogens, which have neuroprotective effects both in vivo and in vitro. However, in an animal model, the actions of estrogens on the hippocampus appear to be somewhat attenuated with age. In the future, estrogen actions over puberty and in pregnancy and lactation should be further explored and should be studied in both the hypothalamus and the extrahypothalamic regions.
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PMID:Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms. 1171 47

The object of this study was to assess the influence of oral contraceptives (OCs) on the risk of cerebral thromboembolic attacks (CTA) including thrombotic stroke and transitory cerebral ischemic attacks. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old suffering a first ever CTA during the period January 1, 1994 to December 31, 1998, were included. Controls were selected annually, 600 per year in 1994-1995, 1200 per year 1996-1998. Response rates for cases and controls were 88% and 90%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic diseases, 626 cases and 4054 controls were available for analysis. A multivariate matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustments were made for the following potential confounders: year, length of OC use, smoking, hypertension, migraine, family CTA, and years of schooling. There were 212 and 1208 current users of OCs among cases and controls, respectively. The risk of CTA among current users of OCs decreased significantly with decreasing estrogen dose (nonusers reference): OCs with 50 microg, 30-40 microg, 20 microg ethinyl estradiol (EE) and progestin-only pills implied adjusted odds ratios (ORs) (95% CI) of 4.5 (2.6-7.7), 1.6 (1.3-2.0), 1.7 (1.0-3.1), and 1.0 (0.3-3.0), respectively. Current users of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins combined with 20-30 microg EE had ORs of CTA of 2.2 (1.6-3.0) and 1.4 (1.0-1.9), respectively. After correction for differences in estrogen dose, the third- to second-generation risk ratio was 0.6 (0.4-0.9; p = 0.01). In conclusion, high dose OCs and OCs with second-generation progestins were associated with the risk of CTA. The risk increased 2.5 times with estrogen dose increasing from 20 to 50 microg EE, and users of low-dose OCs with second-generation progestins had a 61% higher risk-association of CTA than users of OCs with third-generation progestins.
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PMID:Contraceptives and cerebral thrombosis: a five-year national case-control study. 1192 41


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