雌二醇減緩了年輕停經後婦女因藥物導致的記憶缺損


  March 27, 2008 (佛羅里達奧蘭多) —最近的一篇研究顯示,雌二醇(estradiol)預防性治療顯著減少了年輕停經婦女因抗膽鹼藥物引起的記憶缺損,但是會增加年長停經婦女的記憶缺損。
  
  Vermont大學醫學院的Julie A. Dumas博士等人在美國老年精神醫學會第21屆年會中就這些結果發表海報,且最近登載於期刊中(Dumas J 等人, Horm Behav. 2008;53:159-169)。
  
  Dumas博士向Medscape精神醫學表示,我們認為雌激素透過膽鹼系統作用,當你比較年輕,你的膽鹼系統完整無傷,你可以發現雌激素造成的好處;當你上了年紀,你的膽鹼系統比較不佳,好處開始減少。這是第一次在人類有實驗證據顯示這個重要觀念。
  
  該研究顯示,停經婦女的認知改變被廣泛報導,但雌激素可以逆轉或預防此一衰退則尚有爭議;研究顯示雌激素對認知的好處存在於65以下以下的婦女,65歲以上者則沒有;動物研究顯示,有完整的膽鹼系統是發揮雌激素效果的必要因素。
  
  之前,研究者報告指出,給予停經婦女3個月的低劑量(每天1-mg) 雌二醇可減少兩個抗膽鹼藥物—毒蕈鹼拮抗劑scopolamine和尼古丁拮抗劑 mecamylamine —引起的對注意力和速度的不良影響。
  
  目前的研究試圖研究探索每天2-mg的雌二醇與膽鹼系統的作用,對年輕和年長停經婦女的腦部記憶的影響。
  
  研究募集了22名認知正常的停經婦女,年紀在50至81歲,她們依照年齡分成兩組:
  * 11 名年輕婦女(平均年紀 55.8 ± 4.3歲;範圍50-62歲)。
  * 11名年長婦女(平均年紀74.3 ± 3.7歲;範圍70-81歲)。
  
  這些人隨機給予17-beta雌二醇(先給予每天1 mg,為期一個月,之後給予每天2 mg,為期兩個月)或者安慰劑三個月;接著給予三天的藥物刺激(scopolamine、mecamylamine或者安慰劑)與腦部情節記憶認知測驗,之後,將兩組婦女進行交換(雌二醇與安慰劑互換)治療三個月之後再進行三次刺激。
  
  情節記憶測驗中,雌二醇預防治療顯著減少了年輕婦女因藥物引起的影響,但是增加了年長婦女的不佳影響。
  
  研究團隊寫道,這些資料顯示,之前的許多研究認為雌激素治療對早期停經婦女的認知表現沒有明顯效果,可能是因為此年紀的婦女沒有明顯的膽鹼功能不佳。
  
  【雌激素治療的"關鍵時刻" 、"最佳時刻"】
  研究團隊的結論是,隨著膽鹼系統老化,雌二醇提供的好處也減少,因此不只須注意初次給予雌二醇的關鍵時刻,也須注意療程要有適當時間,而後續還需更多研究加以確認。
  
  在一篇相關的海報中,Vermont大學醫學院的Paul A. Newhouse醫師等人表示,初步資料認為,加入黃體素到雌二醇可以部分或完整中和雌激素對促進心理動作速度、反應時間、膽鹼阻斷之後腦部記憶等的能力。
  
  Newhouse博士向Medscape精神醫學表示,雌二醇看似在某種程度上改善了膽鹼功能,黃體素可以阻斷它,這不全然令人驚訝,因為雌激素和黃體素在某些組織的效果是相反的;他指出,使用藥物可以讓研究者發現在年輕停經婦女可能錯過的反應,藉由這些藥物讓膽鹼系統暫時老化,你在幾小時之後就可以這樣做,突然間就發現了雌激素的好處。
  
  美國老年精神醫學會第21屆年會:海報26和27。2007年3月14-17日。

Estradiol Blunts Drug-Induced<

By Marlene Busko
Medscape Medical News

March 27, 2008 (Orlando, Florida) — Estradiol pretreatment significantly attenuated anticholinergic drug–induced memory impairment in younger postmenopausal women, but it increased the impairment in older postmenopausal women, in a recent study.

These results, by Julie A. Dumas, MD, from the University of Vermont College of Medicine, in Burlington, and colleagues, were presented in a poster here at the American Association for Geriatric Psychiatry 21st Annual Meeting and were recently published (Dumas J et al. Horm Behav. 2008;53:159-169).

"We think that estrogen is working through the cholinergic system," Dr. Dumas told Medscape Psychiatry. "When you are younger, your cholinergic system is intact, and you can see good effects of estrogen. When you age, your cholinergic system is more impaired, and there start to be no benefits. . . . This is the first experimental evidence in humans to show this critical idea."

Cognitive changes in postmenopausal women have been widely reported, but whether or not estrogen can reverse or prevent this decline is controversial, the group writes. Studies have shown beneficial effects of estrogen on cognition in women younger than 65 years but not in women older than 65 years. Animal studies have shown that an intact cholinergic system is necessary to see a beneficial effect of estrogen.

Previously, the researchers showed that 3 months of low-dose (1-mg/day) estradiol administered to postmenopausal women reduced the impairment induced by 2 anticholinergic drugs — the muscarinic antagonist scopolamine and the nicotinic antagonist mecamylamine — in tests of attention and speed.

The current study sought to investigate how 2-mg/day estradiol interacts with the cholinergic system to affect verbal memory in younger and older postmenopausal women.

The study recruited 22 cognitively normal postmenopausal women ages 50 to 81 years. The subjects were stratified into 2 age groups:

  • 11 younger women (mean age 55.8 ± 4.3 years; range, 50 to 62 years).
  • 11 older women (mean age 74.3 ± 3.7 years; range, 70 to 81 years).

Subjects were randomly assigned to receive 17-beta estradiol (1 mg/day for 1 month followed by 2 mg/day for 2 months) or placebo for 3 months. The subjects then completed 3 days of drug challenges (scopolamine, mecamylamine, or placebo) with cognitive testing of verbal episodic memory. After this, the women were switched to the other treatment (estradiol or placebo) for 3 months followed by 3 challenges.

Estradiol pretreatment significantly reduced the drug-induced impairment on a test of episodic memory (the Buschke Selective Reminding Task) for the younger women, but it increased the impairment in this test in the older women.

These data suggest that part of the reason several prior studies have not seen significant effects on cognitive performance in the early postmenopausal period with estrogen therapy may be the lack of significant cholinergic impairment at this age, the group writes.

"Critical Period," "Optimal Time" for Estrogen Therapy

"As the cholinergic system ages, the ability of [estradiol] to provide sustained benefit may decline and thus not only may there be a critical period for initiation and administration of [estradiol], but there may be an optimal length of time," the group concludes, adding that this time remains to be determined in further research.

In a related poster, Paul A. Newhouse, MD, from the University of Vermont College of Medicine, and colleagues showed that preliminary data suggest that the addition of progesterone to estradiol appears to partially or completely counteract the ability of estrogen to enhance psychomotor speed, reaction time, and verbal memory after cholinergic blockade.

"It looks like estradiol improves cholinergic functioning to some extent, and progesterone tends to block that, which isn't totally surprising, because estrogen and progesterone have opposite effects in some tissues, Dr. Newhouse told Medscape Psychiatry. Using a pharmacologic challenge enables the researchers to see a response that they might otherwise miss in younger postmenopausal women, he added. "By temporarily 'aging' the cholinergic system with these drugs, which you can do for a few hours, now all of a sudden the estrogen benefit can get expressed," he added.

American Association for Geriatric Psychiatry 21st Annual Meeting: Posters 26 and 27. March 14-17, 2007.

    
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