2010年8月30日 星期一

[tg-woman] Effects of Estrogen: Estrogen and the Brain

Effects of Estrogen: Estrogen and the Brain
雌激素與大腦

Estrogen directly influences brain function through estrogen receptors located on neurons in multiple areas of the brain. The hormone also appears to have direct membrane-mediated effects on neurons. Its effects are both neuroprotective and neurotrophic. Estrogen has been shown to protect isolated neurons in vitro from oxidative stress, ischemic injury, hypoglycemic injury, and damage by amyloid protein, which is implicated in the pathogenesis of Alzheimer's disease. It also stimulates production of nerve growth factors, thereby promoting neuronal growth and viability, repair of damaged neurons, and dendritic branching. Brain aging and Alzheimer's disease are thought to represent an imbalance between neuronal injury and repair.
雌激素直接影響腦功能,通過雌激素受體位於神經元在多個領域的大腦。這種激素似乎也有直接膜介導的神經元的影響。它的影響都是神經保護和神經營養。雌激素已被證明,以保護神經細胞的體外分離氧化應激,缺血性損傷,降血糖損傷,損傷澱粉樣蛋白,這是牽涉在發病阿爾茨海默氏病。它也刺激生產的神經生長因子,從而促進神經細胞生長和活力,修復受損神經元,樹突分枝。腦老化與阿爾茨海默氏症被認為反映了神經元之間的不平衡損傷與修復。

At neuronal synapses, estrogen increases the concentration of neurotransmitters such as serotonin, dopamine, and norepinephrine. It affects their release, reuptake, and enzymatic inactivation. It also increases the number of receptors' for these neurotransmitters.
在神經細胞突觸,雌激素濃度增加,如神經遞質血清素,多巴胺和去甲腎上腺素。它影響到他們的釋放,再攝取和酶失活。它還增加了多少受體的這些神經遞質。

Another significant effect of estrogen on the brain is its influence on blood supply. Unlike many other organs, which can use reserve fuel sources or alternative metabolic pathways, the brain depends solely on blood flow to function. In fact, roughly one-third of the brain is composed of blood vessels. Estrogen increases cerebral perfusion, presumably by mechanisms similar to those known to occur in the coronary arteries. By binding to receptors in the endothelium, estrogen stimulates the release of nitric oxide, which causes vasodilation.
另一個重要的影響雌激素對大腦的影響血液供應。與許多其他器官,它可以使用備用燃料來源或替代代謝途徑,完全取決於大腦的血流量的功能。事實上,大約三分之一的大腦是由血管。雌激素增加腦血流灌注,可能通過類似的機制,已知發生在冠狀動脈。通過結合受體在血管內皮細胞,雌激素刺激一氧化氮的釋放,這會導致血管舒張。

Recent studies have documented the vasodilatory effect of estrogen. Using Doppler flow ultrasound, Penotti et al. examined the carotid and cerebral arteries of 120 women aged 20 to 59 years who were not taking any hormones. Compared with the premenopausal women participating in the study, the postmenopausal women exhibited a significant decrease in blood flow, and flow decreased further with time past menopause. No significant decrease was attributable to aging alone. Another Doppler flow study of 63 postmenopausal women before and after starting ERT demonstrated that this hormonal therapy reduced impedance to blood flow in carotid circulation. Improvement in perfusion was significant by the second month of ERT, and a gradual increase in perfusion continued over the entire 52 weeks of the study.
最近的研究證明雌激素的血管舒張作用。利用多普勒超聲,佩諾蒂等。檢查頸動脈和腦動脈的120名婦女 20歲到59歲誰不服用任何激素。相對於絕經前婦女參加的研究中,絕經後婦女表現出顯著減少血流量,流量進一步下降,隨著時間過去更年期。沒有顯著下降的原因是老化的孤獨。另一個多普勒血流研究絕經後婦女 63前後開始應急小組證明這種荷爾蒙治療,以減少阻抗血流頸動脈循環。在灌注顯著改善了2個月的應急小組,並逐步增加灌注繼續在整個 52週的研究。

Estrogen also influences cerebral blood supply by acting as an anti-inflammatory agent at the blood vessel wall, protecting it from damage by cytokines and free radicals and impeding plaque formation. Pretreatment with estrogen has been demonstrated to prevent damage to blood vessel walls when a toxic protein is injected into rats' cerebral arteries. MRI was used to document ischemic brain injury in 210 postmenopausal women followed for 10 years. The 70 women taking ERT in this study had fewer and smaller damaged areas than the 140 controls.
雌激素也影響腦的血液供應作為一種抗發炎劑在血管壁上,保護它免受損壞的細胞因子和自由基,阻止斑塊形成。雌激素預處理已經證明,以避免破壞血管壁時,毒蛋白注入大鼠腦動脈。磁共振成像是用來記錄缺血性腦損傷的210絕經後婦女隨訪 10年。應急小組的70名婦女參加本研究較少和規模較小的破壞地區超過 140個控制。

In addition, the longer the duration of ERT use, the smaller the total area of ischemia.
此外,持續時間越長,使用的應急小組,總面積越小缺血。

Hot Flushes 潮熱

Hot flushes, the classic symptom of menopause, are experienced by up to 85% of perimenopausal women. (Perimenopause begins several years before menopause, when ovarian function starts to decline, and continues for several years after menopause, until ovarian function has reached its nadir.) A hot flush consists of a sudden sensation of heat in the upper body, often followed by perspiration and a chill. Peripheral vasodilation, tachycardia, decreased skin resistance, and sweating have all been documented to occur during a hot flush. Although poorly understood, the episodes certainly originate in the brain, most likely as a direct response to hypoestrogenism in the thermoregulatory center of the hypothalamus.
潮熱,更年期的典型症狀,有經驗的高達 85%的圍絕經期婦女。 (圍絕經期絕經前幾年開始,當卵巢功能開始下降,並持續了數年後,更年期,卵巢功能,直到到了谷底。)甲潮熱包括突然感覺熱的上半身,經常其次汗水和寒冷。周圍血管舒張,心動過速,皮膚電阻下降,盜汗等,都被記錄下來,以發生在一個炎熱的沖洗。雖然知之甚少,情節當然起源於大腦,最有可能作為一個直接反應在體溫調節 hypoestrogenism中心的地位,下丘腦。

It now appears that hot flushes are not merely symptoms of low estrogen levels; they may themselves lead to other neurologic problems. In oophorectomized women, hot flushes have been directly correlated with memory impairment. In addition, single proton emission computed tomography (SPECT) of healthy menopausal women revealed decreased cerebral blood flow during hot flushes. The greatest change occurred in the hippocampus, a center for memory and cognition. Regional patterns of cerebral blood flow during hot flushes resembled those characteristic of Alzheimer's disease. ERT resolved the hot flushes and restored normal patterns of cerebral blood flow.
現在看來,不只是潮熱症狀的雌激素水平低,他們本身可能導致其他神經系統的問題。在卵巢切除婦女,潮熱有直接相關的記憶障礙。此外,單光子發射計算機斷層掃描(SPECT)檢查顯示,更年期婦女健康的腦血流減少在潮熱。最大的變化發生在海馬,中心記憶和認知。區域格局中的腦血流潮熱相似的特徵阿爾茨海默氏病。應急小組解決了潮熱,恢復正常腦血流模式。

Based on this evidence, reproductive biologists have hypothesized that hot flushes contribute to degenerative or aging changes in the brain.
根據這一證據,生殖生物學家們推測,潮熱有助於退行性改變或老化的大腦。

Frequent vasoconstrictive episodes might lead to cerebral ischemia and free radical formation. The resulting damage may be analogous to that seen in the coronary arteries with plaque formation. The population of healthy neurons might be reduced, particularly in the hippocampus, leaving the brain with impaired ability to tolerate the neurodegenerative processes of aging and Alzheimer's disease.
頻繁發作可能會導致血管收縮對腦缺血和自由基的形成。由此產生的損害可能是類似的出現在與冠狀動脈斑塊的形成。人口的健康神經細胞可能會減少,特別是在海馬,使大腦忍受能力受損的神經退化過程的老化和老年癡呆症。

Estrogen and Cognition 雌激素與認知

Even in healthy older women, brain volume begins to decline as estrogen levels fall in the perimenopausal period. This atrophy occurs particularly in the hippocampus and parietal lobe, areas primarily associated with memory and cognition. A similar loss in brain volume does not begin in men until a decade later (around age 60), most likely because male sex hormone production declines much more gradually with age. In fact, because of aromatization of testosterone to estrogen, men over the age of 60 have approximately three times more circulating estradiol than women of a similar age.
即使在健康的老年婦女,大腦體積開始下降,原因是雌激素水平下降在圍絕經期。這種萎縮的發生,特別是在海馬和頂葉的領域,主要與記憶和認知。類似的腦容量損失不男人開始,直到10年後(約 60歲),很可能是因為男性荷爾蒙產量下降更逐漸隨著年齡的。事實上,由於雌激素睾酮芳構化,男性60歲以上的有大約 3倍循環比女性雌激素有類似的年齡。

In women, these cerebral changes may contribute to the frequent perimenopausal complaints of decreased mental clarity and short-term, verbal memory problems. Studies of the effects of ERT on cognitive symptoms have generated inconsistent results, perhaps because dropouts and nonparticipants are more likely to be cognitively impaired. A recent meta-analysis yielded only weak evidence that ERT improves cognition and prevents dementia. However, many research groups have found a significant association between ERT and cognition, particularly in the area of verbal memory. For example, in one study of 727 postmenopausal women, history of estrogen use was associated with significantly higher scores on verbal memory and abstract reasoning tests.
對女性而言,這些變化可能有助於腦頻繁更年期投訴下降頭腦清晰和短期,言語記憶問題。研究了影響應急小組對認知症狀已經產生不一致的結果,也許是因為輟學和nonparticipants更可能是認知障礙。最近的一項薈萃分析產生只有疲軟的證據表明,應急小組提高認識,防止老年癡呆症。然而,許多研究小組發現了一個重大的ERT和認知之間的關聯,特別是在該地區的口頭記憶。例如,在一項研究中對 727絕經後婦女,雌激素使用史是可以顯著降低分數較高的言語記憶和抽象推理測試。

Shaywitz et al. used positron emission tomography to observe brain activity in 46 postmenopausal women performing cognitive tasks. In a crossover design, participants were given conjugated equine estrogens (CEE; 1.25 mg) or an identical placebo for 21 days, then, after a washout period, given the opposite treatment. During the cognitive tasks, women taking CEE demonstrated increased activation of areas involved in verbal and nonverbal memory.
Shaywitz等。利用正電子發射斷層掃描,觀察大腦活動在46個停經後婦女從事認知任務。在交叉設計,參加者共軛雌激素(中歐和東歐; 1.25 mg)或安慰劑相同為 21天,然後,經過沖洗時期,由於相反的待遇。在認知任務,中歐和東歐的婦女服用增加活化表現領域涉及語言和非語言的記憶。

Loss of cognitive function also can be related to endogenous estrogen deficiency. In the Study of Osteoporotic Fractures, women in the lowest quintile for bone density also exhibited the highest incidence of dementia. In another study, premenopausal women who underwent oophorectomy, which results in abrupt and severe decline in estrogen levels, were more likely than naturally postmenopausal women to exhibit memory impairment five years later. Decline in cognitive function has been observed as early as 2 months postoperatively, and has been shown to be reversible with ERT.
認知功能的喪失也可以與內源性雌激素的不足。在骨質疏鬆性骨折的研究,婦女在最低五分之一的骨質密度也展示了老年癡呆症發病率最高。在另一項研究,絕經前婦女誰接受卵巢切除術,而引起的突然和嚴重的雌激素水平下降,更可能比自然絕經後婦女表現出記憶障礙的五年之後。認知功能下降,據觀察,早在術後 2個月,並已被證明是可逆的藥物治療。

Another effect of menopause and loss of estrogen on the brain is a slowdown in the speed of brain processing. This change is particularly significant for postural stability, which depends on recognition of sensory input and initiation of an appropriate physical response. After menopause, the incidence of falls among women is three times that of men. The risk of fracture in women with osteoporosis appears to be related not only to bone density, but also to postural stability.
另一個影響和損失的更年期雌激素對大腦的速度放緩對大腦處理。這是特別重要的姿勢穩定,這取決於承認感覺輸入和啟動一個適當的生理反應。絕經後的婦女跌倒的發生率是男性的3倍。骨折的危險與骨質疏鬆症的婦女似乎不僅關係到骨骼的密度,而且姿勢的穩定。

Brain processing speed and postural stability are significantly improved with ERT. One study documented a 60% decreased risk of falling in a group of postmenopausal women on ERT compared with a group not taking it. Another study compared sway velocity (an indicator of tendency to fall) in 16 postmenopausal long-term users of 17 b-estradiol and 16 postmenopausal women who had never taken estrogen. The postmenopausal women taking estrogen evidenced postural stability similar to premenopausal women, whereas balance deteriorated significantly in the postmenopausal women not on ERT. The fact that ERT improves both postural stability and bone density likely explains why it has proven superior to raloxifene and alendronate in preventing nonvertebral, fall-related fractures.
腦的處理速度和姿勢的穩定性顯著改善了藥物治療。一項研究記錄了60%,降低風險降組中的絕經後婦女的應急小組較一組不服用。另一項研究比較晃動速度(一指標下降的趨勢)在16絕經後長期使用的17β-雌二醇和16絕經後婦女雌激素誰從來都不曾有過。絕經後婦女服用雌激素的姿勢穩定證明類似絕經前婦女,而平衡嚴重惡化的絕經後婦女沒有藥物治療。事實上,既提高了應急小組姿勢穩定和骨質密度可能解釋了為什麼它已被證明優於雷洛昔芬和阿崙膦酸鈉預防非脊椎,秋天有關的骨折。

Estrogen and Mood 雌激素與情緒

In general, perimenopausal women do not appear to be more susceptible to clinical depression than women at other life stages. However, in certain groups of women, including those with a history of postpartum or premenstrual depression, those who undergo the abrupt hormonal changes of surgical menopause, and those in whom perimenopause is prolonged, risk for depression may be increased during this time. In addition, up to 80% of perimenopausal women develop mild depressive symptoms beyond the malaise that might be attributed to hot flushes, night sweats, and insomnia. These symptoms may occur because areas of the brain involved in emotion are rich in estrogen receptors and estrogen directly influences synaptic concentrations of neurotransmitters.
在一般情況下,圍絕經期婦女不顯得更容易受到抑鬱症的臨床比女性在其他生命階段。但是,在某些婦女群體,包括那些有歷史的或經前產後抑鬱症,那些誰接受了手術突然停經荷爾蒙變化,而這些人在圍絕經期的延長,抑鬱症的風險可能會增加在這段時間。此外,高達 80%的更年期婦女抑鬱症狀的發展超出了輕度不適,可能是由於潮熱,盜汗,失眠。這些症狀可能是因為大腦中涉及的領域,在情感上有豐富的雌激素受體和雌激素的濃度直接影響突觸的神經遞質。

The neurotransmitter serotonin plays a key role at brain synapses involved in mood regulation. In oophorectomized rats, administration of estradiol induced a significant increase in serotonin uptake in the frontal cortex and hypothalamus. Also in rats, the antidepressant imipramine did not exert its therapeutic effect on synaptic concentrations of serotonin unless estrogen was present.
羥色胺神經遞質起著關鍵作用,在大腦突觸參與調節情緒。在卵巢切除大鼠,管理雌二醇誘導顯著增加血清素攝取的額葉皮質和下丘腦。此外,在大鼠的抗抑鬱藥丙咪嗪,沒有發揮其治療作用的突觸雌激素濃度的血清素,除非出席。

In women of reproductive age, serum estradiol levels have been shown to correlate positively with blood levels of serotonin. Researchers have also demonstrated that blood serotonin is decreased in postmenopausal women and that ERT raises it to premenopausal levels. Estrogen also competes with tryptophan, the precursor of serotonin, for binding sites on plasma albumin, thus making tryptophan more available to the CNS.
在育齡婦女,血清雌二醇水平已表現出顯著的正向與血液中血清素。研究人員還表明,血液中的血清素降低絕經後婦女,應急小組提出了到絕經前的水平。雌激素還與色氨酸競爭,血清素的前體,為血漿白蛋白結合位點,從而使色氨酸更提供給中樞神經系統。

Estrogen affects concentrations of other neurotransmitters and neuromodulators as well. It competitively inhibits the enzyme that inactivates norepinephrine, thus providing a stimulatory effect similar to that of many antidepressant medications. Like pharmaceutical monoamine oxidase (MAO) inhibitors, estrogen reduces MAO activity, resulting in higher levels of both catecholamines and serotonin in the brain. Estrogen also increases opioid and endorphin production by the hypothalamus.
雌激素濃度的影響其他神經遞質和調質以及。它競爭性抑制酶失活去甲腎上腺素,從而提供了一種刺激作用類似於許多抗抑鬱藥物。單胺氧化酶一樣製藥(MAO)的抑製劑,雌激素降低 MAO活性,導致雙方在更高水平的兒茶酚胺和五羥色胺在大腦中。雌激素也會增加阿片類藥物的生產和內啡肽由下丘腦。

Clinically, women taking the selective estrogen receptor modulator tamoxifen and women on gonadotropin-releasing hormone therapy, which induces hypoestrogenism, have been shown to exhibit increased depressive symptomatology. In randomized controlled trials oophorectomized and perimenopausal women undergoing ERT have experienced a heightened sense of well-being and improved mood. A recent meta-analysis of 26 studies in postmenopausal women found that ERT had a moderate-to-large beneficial effect on depressed mood. This positive effect often was not apparent until after 3 months of treatment, was dampened by the addition of a progestin, and was enhanced by supplementation with an androgen.
臨床上,婦女服用雌激素受體調節劑選擇性三苯氧胺和婦女促性腺激素釋放激素治療,誘導 hypoestrogenism,已被證實具有增加抑鬱症狀。在隨機對照試驗圍絕經期婦女接受卵巢切除和專家審評組經歷了提高意識的福祉和改善心情。最近的一項薈萃分析研究,絕經後婦女 26日發現,應急小組有中到大的有利影響抑鬱情緒。這種積極的作用往往並不明顯,直到3個月的治療後,被壓抑的另外一個孕激素,並加強了與雄激素補充。

Estrogen and Alzheimer's Disease  雌激素與阿爾茨海默氏病

With the aging of the "baby boom" generation and increasing life expectancy, dementia has become a significant social and economic problem in the United States. Alzheimer's disease, a progressive disorder that impairs memory, thinking, and behavior, accounts for two-thirds of these dementia cases. The disease is two to three times more common in women, a fact not fully explained by the reality that women live longer on average than men.
隨著老齡化的"嬰兒潮"一代和增加壽命,老年癡呆症已成為一個重大的社會和經濟問題在美國。阿爾茨海默氏症,一個先進的疾病,損害記憶,思維和行為,佔三分之二的這些癡呆症的發生。這種疾病是2至3倍多見於女性,其實並沒有完全解釋現實生活,女性平均比男性長。

The cognitive difficulties of Alzheimer's disease patients appear to be related to the presence of abnormal protein deposits in the brain. Accumulations of an abnormal, neurotoxic form of b-amyloid is characteristic of the disease. Increasing evidence implicates inflammation in the pathogenesis of Alzheimer's disease. b-amyloid fragments and other proteins may be either the cause or an effect of an exaggerated inflammatory response to brain or cerebral blood vessel injury. This theory is supported by the fact that anti-inflammatory drugs appear to provide some protection against Alzheimer's disease.
認知困難,阿爾茨海默氏症患者的出現可能與存在的異常蛋白沉積在大腦中。積累的異常,神經形成的b -澱粉樣蛋白是特徵的疾病。越來越多的證據蘊涵炎症的發病阿爾茨海默氏病。 β-澱粉樣蛋白片段和其他任何可能的原因或誇大效果的炎症反應到大腦或腦血管損傷。這一理論是支持的事實,消炎藥似乎提供一些保護防止老年癡呆症。

Alzheimer's disease is at least partly genetic in origin. The early-onset variety, which accounts for only 5% of cases, can be traced to autosomal dominant mutations in genes encoding for presenilin protein or amyloid protein. Late-onset Alzheimer's, which represents the vast majority of cases, occurs after age 60. This type can be related to multiple factors, including defects in several "susceptibility genes." The most common of these, a recessive gene located on chromosome 19, codes for apolipoprotein E, which aids in repairing damaged neurons.
阿爾茨海默氏病是至少部分是遺傳起源。早期發病品種,佔只有5%的情況下,可以追溯到常染色體顯性遺傳突變基因編碼早老蛋白或澱粉樣蛋白。晚發性阿爾茨海默氏症,它代表了絕大多數案件中,60 歲以後發生。這種類型可能與多種因素,包括缺陷的幾個"易感基因。"最常見的,其中一個隱性基因位於 19號染色體,編碼載脂蛋白E,其中艾滋病在修復受損神經元。

Approximately 15% to 20% of persons of European descent carry at least one abnormal copy of this gene. Whether it is expressed or not depends on multiple factors including female gender, low educational attainment, prior head injury, lack of exposure to anti-inflammatory agents, and, for women, lack of estrogen after menopause.
大約 15%至20%的歐洲血統的人至少攜帶一個這種基因異常的副本。無論是明示或不取決於多種因素,包括女性,低教育程度,事先頭部受傷,缺乏接觸消炎藥,而且,對於婦女,絕經後雌激素缺乏。

Estrogen levels might affect the course of Alzheimer's disease in several ways. Because the disease is thought to be inflammatory in nature, loss of estrogen and its anti-inflammatory effects might contribute to the development of Alzheimer's disease. Conversely, increased cerebral blood flow, along with neurotrophic and neuroprotective effects,might render the brain more resistant to the disease process. In addition, estrogen appears to have the ability to increase expression of the apolipoprotein E gene and reduce formation of b-amyloid.
雌激素水平可能會影響這一過程中,阿爾茨海默氏病的幾種方法。由於這種疾病被認為是炎症性的,其損失的雌激素和抗炎作用可能有助於開發阿爾茨海默氏病。相反,增加腦血流量,以及神經營養和神經保護作用,可能會使大腦更能抵抗這種疾病的進程。此外,雌激素似乎有能力增加表達載脂蛋白E基因和減少形成的b -澱粉樣蛋白。

Almost all epidemiologic studies performed thus far indicate that ERT can prevent or delay onset of Alzheimer's disease. In the most recent, the Italian Longitudinal Study on Aging, 2,816 randomly selected postmenopausal women were tested for Alzheimer's disease and senile dementia. Those who had ever used ERT had a 70% reduction in Alzheimer's disease risk, even when the data were adjusted for age, age at menopause, education, smoking, alcohol use, and parity.
幾乎所有的流行病學研究表明,迄今進行的專家審評組可以預防或延緩老年癡呆症發病的疾病。在最近,意大利的縱向研究老齡問題,絕經後婦女隨機選擇 2816進行了測試對阿爾茨海默氏症和老年癡呆症。這些誰曾經使用了一個應急小組的70%減少阿爾茨海默氏症的風險,即使數據進行了調整年齡,絕經年齡,教育,吸煙,飲酒,和平等。

The largest study on ERT involved women from the Leisure World retirement community in southern California. A review of death certificates revealed that women who had ever taken ERT were one-third less likely to develop Alzheimer's disease. Moreover, the risk of Alzheimer's disease decreased significantly with increasing estrogen dose and with increasing duration of estrogen use.
最大的婦女研究專家審評組的休閒世界退休社區在南加州。綜述死亡證明書表明,婦女誰曾經採取了應急小組是三分之一不太可能發展阿爾茨海默氏症。此外,風險阿爾茨海默病顯著降低雌激素劑量的增加,並隨時間的雌激素的使用。

The Baltimore Longitudinal Study of Aging is the only prospective study done thus far, and, although relatively small, it demonstrated the most dramatic effect to date. In 472 perimenopausal and postmenopausal women followed for 16 years, the risk of Alzheimer's disease was reduced by 54% in women who reported having ever used ERT.
巴爾的摩縱向老化研究是唯一迄今為止所做的前瞻性研究,而且,雖然相對較小,它體現了最戲劇性效果的日期。在圍絕經期和絕經後婦女 472隨訪 16年,風險阿爾茨海默病減少了54%的婦女報告說,誰使用過藥物治療。

Interestingly, reduced risk of Alzheimer's disease has been demonstrated even in women who take ERT only during the menopausal transition, presumably to prevent hot flushes. One group of researchers observed a 50% decrease in the disease in women on ERT for less than 1 year at the time of menopause. This finding implies that neurons may be particularly susceptible to damage following an abrupt drop in estrogen levels and that, once damaged, neurons may be less able to respond to ERT. In a randomized, controlled trial in which 120 patients with established Alzheimer's disease received CEE 0.625 mg, CEE 1.25 mg, or placebo for 1 year, ERT failed to demonstrate a therapeutic effect. However, ERT may potentiate the therapeutic effects of tacrine on the disease.
有趣的是,減少風險的阿爾茨海默氏症已被證明即使是在婦女誰採取應急小組只在絕經過渡期,可能是為了防止潮熱。一組研究人員觀察了50%,減少這種疾病在婦女應急小組不到一年的時間在更年期。這一發現意味著,神經元可能特別容易受到損傷的一雌激素水平急劇下降,而且,一旦受損,神經元可能不太能夠應對藥物治療。在一項隨機,對照試驗中,120例患者按照既定阿爾茨海默氏症獲得 0.625毫克東歐,中歐和東歐 1.25毫克,或安慰劑,為期 1年,應急小組未能顯示出療效。然而,專家審評組可能發揮了重要作用他克林治療的疾病。

Research on ERT and Alzheimer's disease is in its early stages, studies to date are retrospective and thus susceptible to bias. Notably, one population-based, case-control study involving 107 Alzheimer's disease patients and 120 age-matched controls failed to show a risk reduction in Alzheimer's disease among women who used ERT. Nevertheless, prevention or delay of Alzheimer's disease appears to be a benefit of ERT that could offer substantial advantages to both women as individuals and society as a whole.
研究ERT和阿爾茨海默氏病是在其早期階段,研究迄今是有追溯力,容易受偏見。值得注意的是,一個人口為基礎的病例對照研究,涉及 107阿爾茨海默氏症患者和120名年齡匹配的對照組未能顯示出風險減少阿爾茨海默氏症的婦女誰使用藥物治療。然而,預防或延緩阿爾茨海默氏症似乎是一個造福應急小組,可以提供大量的優勢,包括婦女作為個人和整個社會。


Estrogen and Parkinson's Disease  雌激素與帕金森氏病


Parkinson's disease is a gradually progressive neurologic disorder characterized by tremor at rest, rigidity, bradykinesia (slowness of movement), and postural instability. In patients with Parkinson's disease, dopamine-producing cells in the part of the brain known as the substantia nigra degenerate. Symptoms usually respond to treatment with levodopa for several years, after which the disease progresses despite this therapy. Recently, estrogen has been shown to potentiate the action of levodopa, and ERT to perhaps delay or prevent the onset of Parkinson's disease.
帕金森氏病是一種神經系統疾病逐漸進步的特點是在休息震顫,僵硬,運動遲緩(緩慢的運動),和姿勢不穩。在患者與帕金森氏病,產生多巴胺的細胞在大腦的一部分,被稱為黑質退化。症狀通常回應左旋多巴治療數年後,這種疾病的進展,儘管這一療法。最近,雌激素已被證明發揮了重要作用左旋多巴,與張力或許推遲或防止發生帕金森氏症。

Animal models suggest numerous mechanisms by which estrogen may positively affect dopamine neurotransmission. Estrogen appears to be neuroprotective to dopamine-producing neurons. It also increases sensitivity of neurons to dopamine and decreases dopamine reuptake at synapses.
動物模型顯示,許多機制,其中雌激素可能影響多巴胺神經傳遞積極。雌激素似乎對神經保護產生多巴胺的神經元。它還增加對多巴胺神經元的敏感性,降低多巴胺在突觸再攝取。

Clinically, estrogen appears to exert a palliative effect on Parkinson's disease. One study correlated estrogen exposure (years of fertility plus years of ERT) with age at onset of Parkinson's disease. On average, women with low estrogen exposure developed the disease 6 years earlier than did women with high exposure. In another study examining the medical histories of women recently diagnosed with Parkinson's disease, women who had taken ERT had significantly later onset of the disease and less severe symptoms. ERT may also enhance cognition, especially memory, in women with Parkinson's disease, and reduce the risk of developing Parkinson's disease-associated dementia.
臨床上,雌激素似乎會對緩解對帕金森氏症。一項研究相關雌激素暴露(年生育率多年的應急小組)的發病年齡帕金森氏症。平均而言,女性低雌激素暴露6年開發的疾病也早於女性高暴露。在另一項研究審查病史的婦女最近確診患有帕金森氏症,婦女誰採取了應急小組,後來才出現了明顯的疾病,症狀較輕。應急小組也可能提高認識,尤其是內存,婦女與帕金森氏症,並降低開發風險帕金森氏症相關癡呆症。

In addition, ERT appears to potentiate the effects of the anti-Parkinson's drug levodopa. Estrogen reduces the expression of catechol-O-methyltransferase (COMT), the enzyme responsible for dopamine degradation. Because reduced COMT activity increases the bioavailability of dopamine, pharmacologic COMT inhibitors are often used to enhance levodopa's effect. Estrogen has been shown to reduce levodopa response threshold, levodopa clearance, and the mean levodopa dose required in women.
此外,專家審評組似乎發揮了重要作用的反帕金森氏症藥物左旋多巴。雌激素減少了表達兒茶酚 - O -甲基轉移酶(COMT)的,這種酶負責多巴胺退化。由於 COMT活性降低生物利用度增加多巴胺,藥理轉移酶抑製劑通常用於加強左旋多巴的作用。雌激素已被證實可以降低左旋多巴的反應閾值,左旋多巴間隙,左旋多巴劑量,平均需要的婦女。

Research on ERT and Parkinson's disease is in its early stages, but results are promising regarding estrogen's effects on delayed onset, symptomatic improvement, and adjunctive treatment of the disease.
研究ERT和帕金森氏病是在其早期階段,但結果是有希望的關於雌激素的影響推遲發病,症狀的改善和輔助治療該病。

Further study of these potential benefits is clearly warranted.
進一步研究這些潛在的好處顯然是必要的。

http://www.medscape.com/viewarticle/406718_2

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