The menopause transition is associated with an increased risk of depressed mood. Preliminary evidence suggests that increased sensitivity to psychosocial stress, triggered by exaggerated perimenopausal estradiol fluctuation, may play a role. However, accurately quantifying estradiol fluctuation while minimizing participant burden has posed a methodological challenge in the field. The current pilot project aimed to test the feasibility of capturing perimenopausal estradiol fluctuation via 12 weekly measurements of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, using participant-collected urine (...) samples in 15 euthymic perimenopausal women ages 45-55 years. Furthermore, it aimed to correlate E1G fluctuation (standard deviation across the 12 E1G measurements) with weekly mood and cardiovascular, salivary cortisol, and subjective emotional responses to the Trier Social Stress Test (TSST) at weeks 4, 8 and 12. Protocol acceptability and adherence was high; furthermore, E1G fluctuation was positively associated with anhedonic depressive symptoms and weekly negative affect. E1G fluctuation was also associated with increased heart rate throughout the TSST as well as higher levels of rejection, anger, and sadness. E1G fluctuation was not significantly associated with TSST blood pressure or cortisol levels. This study suggests a feasible method of assessing estradiol fluctuation in the menopause transition and provides support for the hypothesis that perimenopausal estradiol fluctuation increases sensitivity to psychosocial stress and vulnerability to depressed mood. (shrink)

Neurosteroid 17 beta-estradiol (E2) is a steroid synthesized de novo in the nervous system that might influence neuronal activity and behavior. Nevertheless, the impact of E2 on the functioning of those neural systems in which it is slightly synthesized is less questioned. The vestibulo-ocular reflex (VOR) adaptation, may provide an ideal arena for investigating this issue. Indeed, E2 modulates cerebellar parallel fiber-Purkinje cell synaptic plasticity that underlies encoding of VOR adaptation. Moreover, aromatase expression in the cerebellum of adult rodents (...) is maintained at very low levels and localized to Purkinje cells. The significance of age-related maintenance of low levels of aromatase expression in the cerebellum on behavior, however, has yet to be explored. Our aim in this study was to determine whether E2 synthesis exerts an effective and persistent modulation of VOR adaptation in adult male rats. To answer this question, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in VOR adaptation using an oral dose (2.5 mg/kg) of the aromatase inhibitor Letrozole in peri-pubertal and post-pubertal male rats. We found that Letrozole acutely impaired gain increases and decreases in VOR adaptation without altering basal ocular-motor performance and that these effects were similar in peri-pubertal and post-pubertal rats. Thus, in adult male rats neurosteroid E2 effectively modulates VOR adaptation in both of the periods studied. These findings imply that the adult cerebellum uses E2 synthesis for modulating motor memory formation and suggest that low and extremely localized E2 production may play a role in adaptive phenomena. (shrink)

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the (...) aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites. (shrink)

Hormonal changes across the menstrual cycle have been shown to influence reward-related motivation and impulsive behaviors. Here, to compare neural mechanisms of cognitive impulse control during the mid-luteal phase (LP) versus during the late follicular phase (FP), we employed functional magnetic resonance imaging (fMRI) with an event-related monetary delay discounting (EMDD) behavioral task (study 1) and then employed resting state (RS)-fMRI (study 2). The imaging data were analyzed and related to behavior-associated neural activation. In study 1, women in the late (...) FP showed a preference for sooner rewards while exhibiting enhanced activity in the dorsal striatum (DS), whereas women in the mid-LP showed a preference for delayed, higher-value rewards with enhanced activity in the dorsolateral prefrontal cortex (dlPFC). Discount rate (transformed k) in the EMDD task correlated with functional connectivity (FC) of the DS-dlPFC circuitry, consistent with the possibility that DS-dlPFC circuitry may regulate impulsivity. In study 2, the right dlPFC was significantly more active in mid-LP than in late FP, and this effect was sensitive to estradiol (E2) and relative E2 levels during mid-LP. The magnitude of DS-dlPFC FC correlated negatively with psychometric impulsivity scores during the late FP. These results replicated findings from study 1 and further indicated that relative E2 levels may play an important role in increasing cognitive control during the mid-LP, which provides new insight into the treatment of conditions characterized by hyper-impulsivity, such as obsessive-compulsive disorder, Parkinson disease, and attention deficit hyperactivity disorder. In conclusion, our results suggest that cyclical gonadal hormones affect cognitive control on impulsive behavior periodically, possibility via DS-dlPFC circuitry. (shrink)

BackgroundWe review original papers on ovarian-hormone status in two areas of emotional processing: facial emotion recognition and emotional memory. Ovarian-hormone status is operationalized by the levels of the steroid sex hormones 17β-estradiol and progesterone, fluctuating over the natural menstrual cycle and suppressed under oral contraceptive use. We extend previous reviews addressing single areas of emotional processing. Moreover, we systematically examine the role of stimulus features such as emotion type or stimulus valence and aim at elucidating factors that reconcile the (...) inconsistent results.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included papers published until September 2020 indexed in PubMed and Web of Science databases. Search terms were MeSH terms AND AND with representing our separately searched areas, resulting in, and. To be included, articles had to be written and published in English, examine healthy, non-pregnant adult women in their reproductive age, and measure or at least estimate levels of E2 and P4. In PubMed, the search was limited to humans and to the search term present in the title or abstract.ResultsFeatures of the provided stimulus material constitute a relevant influence that interacts with E2- and P4-related ovarian-hormone status. For instance, recognition of basic emotions appears to be more related to P4- than E2-levels. Quite consistent, OC intake was accompanied by impaired recognition accuracy of basic and also complex emotions, although not in a recent large-sample study assessing complex emotions. Memory recall of negative content was mainly enhanced by P4, especially after having been stressed.Discussion and ConclusionWe document the methodological diversity in the field, presumably contributing to the heterogeneity of results. More studies explicitly contrasting the early follicular phase, mid-cycle phase, mid-luteal, and OC intake while standardizing tasks are needed. Research would take advantage of using within-subject designs and accounting for the recognition of complex emotions. (shrink)