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Menstrual phase-dependent differences in neurobehavioral performance: the role of temperature and the progesterone/estradiol ratio.

ABSTRACT: STUDY OBJECTIVES:Women in the luteal phase of the menstrual cycle exhibit better cognitive performance overnight than women in the follicular phase, although the mechanism is unknown. Given the link between core body temperature (CBT) and performance, one potential mechanism is the thermoregulatory role of progesterone (P4), estradiol (E2), and their ratio (P4/E2), which change across the menstrual cycle. We examined the role of P4/E2 in modulating performance during extended wake in premenopausal women. Additionally, we compared the acute effects of nighttime light exposure on performance, CBT, and hormones between the menstrual phases. METHODS:Participants were studied during a 50 h constant routine and a 6.5 h monochromatic nighttime light exposure. Participants were 16 healthy, naturally cycling women (eight follicular; eight luteal). Outcome measures included reaction time, attentional failures, self-reported sleepiness, CBT, melatonin, P4, and E2. RESULTS:As compared to women in the luteal phase, women in the follicular phase exhibited worse performance overnight. CBT was significantly associated with performance, P4, and P4/E2 but not with other sex hormones. Sex hormones were not directly related to performance. Light exposure that suppressed melatonin improved performance in the follicular phase (n = 4 per group) to levels observed during the luteal phase and increased CBT but without concomitant changes in P4/E2. CONCLUSIONS:Our results underscore the importance of considering menstrual phase when assessing cognitive performance during sleep loss in women and indicate that these changes are driven predominantly by CBT. Furthermore, this study shows that vulnerability to sleep loss during the follicular phase may be resolved by exposure to light.

SUBMITTER: Grant LK

PROVIDER: S-EPMC7457328 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Menstrual phase-dependent differences in neurobehavioral performance: the role of temperature and the progesterone/estradiol ratio.

Grant Leilah K LK Gooley Joshua J JJ St Hilaire Melissa A MA Rajaratnam Shantha M W SMW Brainard George C GC Czeisler Charles A CA Lockley Steven W SW Rahman Shadab A SA

Sleep 20200201 2

<h4>Study objectives</h4>Women in the luteal phase of the menstrual cycle exhibit better cognitive performance overnight than women in the follicular phase, although the mechanism is unknown. Given the link between core body temperature (CBT) and performance, one potential mechanism is the thermoregulatory role of progesterone (P4), estradiol (E2), and their ratio (P4/E2), which change across the menstrual cycle. We examined the role of P4/E2 in modulating performance during extended wake in pre ...[more]

PMID: 31670824

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Project description:IntroductionWomen are at a higher risk of developing Alzheimer's disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade.MethodsTwenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory.ResultsSignificant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade.DiscussionThe findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

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Dataset Information

Menstrual phase-dependent differences in neurobehavioral performance: the role of temperature and the progesterone/estradiol ratio.

Publications

Menstrual phase-dependent differences in neurobehavioral performance: the role of temperature and the progesterone/estradiol ratio.

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