Effects of the experimental administration of oral estrogen on prefrontal functions in healthy young women

Effects of the experimental administration of oral estrogen on prefrontal functions in healthy young women
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实验性口服雌激素对健康年轻女性前额叶功能的影响

DOI:
10.1007/s00213-018-5061-y
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发表时间:
2018
期刊:
影响因子:
3.4
通讯作者:
Bayer J
Bayer J
中科院分区:
医学3区
文献类型:
--
作者:
Sommer T;Richter K;Singer F;Derntl B;Rune GM;Diekhof E;Bayer J

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17-β-雌二醇(E2)刺激前额叶皮层的神经可塑性和多巴胺能传递,这与注意力控制、工作记忆和其他执行功能密切相关。在月经周期或激素替代治疗过程中,研究E2对额前介导行为的作用是不确定的,有许多无效的发现以及有益和有害的影响。目前的研究集中在E2对注意力表现的影响上,因为动物研究表明,超生理剂量(即,高于动情周期水平)的E2对雌性啮齿动物的注意力测量具有有益的影响。为了将这些发现转化为人类,我们采用随机、双盲、前后设计,对34名处于低激素早期卵泡期的自然周期女性口服12 mg E2-戊酸或安慰剂。在基线和E2峰值期间测试两次行为表现,其中E2水平在E2组中达到轻度超生理水平。除了主要由前额叶介导的注意力、工作记忆和其他执行功能的任务外,我们还采用了情感调节注意力、情绪识别和言语记忆的任务。E2给药对一般处理速度和工作记忆表现有显著但微妙的负面影响。这些影响可能与多巴胺能传递的过度刺激有关。超生理E2对工作记忆的负面影响与动物文献有很好的联系。对注意力表现或任何其他测量都没有影响。这可能是因为不同的E2水平对于改变特定任务中的行为表现是最佳的,这可能取决于所涉及的大脑区域。
17-Beta-estradiol (E2) stimulates neural plasticity and dopaminergic transmission in the prefrontal cortex, which is critically involved in attentional control, working memory, and other executive functions. Studies investigating E2’s actions on prefrontally mediated behavior in the course of the menstrual cycle or during hormone replacement therapy are inconclusive, with numerous null findings as well as beneficial and detrimental effects. The current study focused on the effect of E2 on attentional performance, as animal studies indicate that supraphysiological doses (i.e., above estrous cycle levels) of E2 have beneficial effects on measures of attention in female rodents. To translate these findings to humans, we administered 12 mg E2-valerate or placebo orally to 34 naturally cycling women in the low-hormone early follicular phase using a randomized, double-blinded, pre-post design. Behavioral performance was tested twice during baseline and E2 peak, where E2 levels reached mildly supraphysiological levels in the E2 group. Aside from mainly prefrontally mediated tasks of attention, working memory, and other executive functions, we employed tasks of affectively modulated attention, emotion recognition, and verbal memory. E2 administration had a significant, but subtle negative impact on general processing speed and working memory performance. These effects could be related to an overstimulation of dopaminergic transmission. The negative effect of supraphysiological E2 on working memory connects well to animal literature. There were no effects on attentional performance or any other measure. This could be explained by different E2 levels being optimal for changing behavioral performance in specific tasks, which likely depends on the brain regions involved.
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DOI: 10.1038/s41467-018-03679-x
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