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


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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The project was supported by a grant of the German Research Foundation (DFG SO 952/6-1), a grant of the state of Hamburg (UHH LFF FV 27), and the German Society for Psychosomatic Obstetrics and Gynecology (Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe; DGPFG).

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Correspondence to Janine Bayer.

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Participants received financial compensation and gave written informed consent according to the Declaration of Helsinki. Ethics approval was obtained from the Ethics Committee of the Hamburg Medical Association (PV3612).

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The authors declare that there is no conflict of interest.

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Sommer, T., Richter, K., Singer, F. et al. Effects of the experimental administration of oral estrogen on prefrontal functions in healthy young women. Psychopharmacology 235, 3465–3477 (2018).

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  • Estrogen
  • Prefrontal functions
  • Attention
  • Working memory
  • Affectively modulated attention
  • Verbal memory
  • Emotion recognition