Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, USA.
Menopause. 2010 Jul;17(4):860-73. doi: 10.1097/gme.0b013e3181e15df4.
Recent studies have shown that women experience an acceleration of cognitive problems after menopause and that estrogen treatment can improve or at least maintain current levels of cognitive functioning in postmenopausal women. However, we have previously shown that the negative emotional effects of psychosocial stress are magnified in normal postmenopausal women after estrogen treatment. This study examined whether estradiol (E2) administration can modify cognitive performance after exposure to psychological stress and monoamine depletion.
Participants consisted of 22 postmenopausal women placed on either oral placebo or 17beta-E2 (1 mg/d for 1 mo, then 2 mg/d for 2 mo). At the end of the 3-month treatment phase, participants underwent three depletion challenges in which they ingested one of three amino acid mixtures: deficient in tryptophan, deficient in phenylalanine/tyrosine, or balanced. Five hours later, participants performed the Trier Social Stress Test (TSST), followed by mood and anxiety ratings and cognitive testing. Cognitive measures included tests of attention, psychomotor function, and verbal episodic memory.
E2-treated compared with placebo-treated participants exhibited significant worsening of cognitive performance on tasks measuring attentional performance and psychomotor speed. Similar trends for impairment were seen in measures of long-term episodic memory compared with placebo-treated postmenopausal women. E2-treated participants also showed a significant increase in negative mood and anxiety compared with placebo-treated women after, but not before, the TSST, although the worsening of both cognitive and behavioral functioning was not correlated. These effects were independent of tryptophan or tyrosine/phenylalanine depletion and were not manifested before the TSST or at baseline.
These data suggest that the relationship between estrogen administration and cognitive/behavioral performance in postmenopausal women may be more complex than initially appreciated and that the effects of psychosocial stress may influence whether hormone effects are beneficial.
最近的研究表明，女性在绝经后会经历认知问题的加速，雌激素治疗可以改善或至少维持绝经后女性当前的认知功能水平。然而，我们之前已经表明，在接受雌激素治疗后，正常绝经后女性的心理社会应激的负面情绪影响会放大。本研究探讨了雌二醇（E2）给药是否可以改变心理应激和单胺耗竭后认知表现。
参与者由 22 名绝经后妇女组成，她们服用口服安慰剂或 17β-E2（1mg/d 持续 1 个月，然后 2mg/d 持续 2 个月）。在 3 个月的治疗阶段结束时，参与者接受了 3 次耗竭挑战，他们摄入了 3 种氨基酸混合物中的一种：色氨酸缺乏、苯丙氨酸/酪氨酸缺乏或平衡。5 小时后，参与者进行了特里尔社会应激测试（TSST），随后进行了情绪和焦虑评分以及认知测试。认知测量包括注意力、精神运动功能和言语情节记忆测试。
与安慰剂治疗的参与者相比，E2 治疗的参与者在注意力表现和精神运动速度的任务上的认知表现明显恶化。与安慰剂治疗的绝经后妇女相比，长期情节记忆的测量也显示出类似的损害趋势。E2 治疗的参与者在 TSST 后也表现出明显的负面情绪和焦虑增加，而在 TSST 前或基线时则没有，尽管认知和行为功能的恶化与安慰剂治疗的女性没有相关性。这些影响独立于色氨酸或酪氨酸/苯丙氨酸耗竭，并且在 TSST 之前或基线时没有表现出来。
这些数据表明，雌激素给药与绝经后妇女认知/行为表现之间的关系可能比最初预期的更为复杂，心理社会应激的影响可能会影响激素效应是否有益。
