Progesterone and mental rotation task: is there any effect?
ABSTRACT: Mental rotation task (MRT) incorporates elements of spatial abilities, important in many professions, with people of both genders involved. Importantly, these are the areas where spatial tasks might be performed for long time periods; thus adverse effects of mental fatigue are highly unwanted. Substantial variation of MRT performance in relation to estrogen levels has been observed in many studies, whereas the role of progesterone remains elusive. Here we aimed to elucidate the effect of progesterone level on the long-duration (1.5 hours) performance of MRT. We included three groups of subjects: a group of males as a control, a group of females in their follicular phase (low progesterone) and a group of females in their luteal phase (high progesterone), MRT accuracy and response time, subjective fatigue ratings and cardiovascular measures together with 17 ? -estradiol and progesterone concentrations were analyzed. We found that subjective ratings of fatigue increased, performance accuracy increased, and mean response times decreased during the task in all groups. Females in luteal phase were significantly slower not only than men, but also than females in their follicular phase. An increase in subjective fatigue ratings was positively related to progesterone level-at higher progesterone levels, females felt more tired.
Project description:Nicotine dependence is a serious public health concern. Optimal treatment of nicotine dependence will require greater understanding of the mechanisms that contribute to the maintenance of smoking behaviors. A growing literature indicates sex and menstrual phase differences in responses to nicotine. The aim of this study was to assess sex and menstrual phase influences on a broad range of measures of nicotine response including subjective drug effects, cognition, physiological responses, and symptoms of withdrawal, craving, and affect. Using a well-established intravenous nicotine paradigm and biochemical confirmation of overnight abstinence and menstrual cycle phase, analyses were performed to compare sex (age 18-50 years; 115 male and 45 female) and menstrual cycle phase (29 follicular and 16 luteal) effects. Females had diminished subjective drug effects of, but greater physiological responses to, nicotine administration. Luteal-phase females showed diminished subjective drug effects and better cognition relative to follicular-phase women. These findings offer candidate mechanisms through which the luteal phase, wherein progesterone is dominant relative to estradiol, may be protective against vulnerability to smoking.
Project description:Subtle changes in social cognition are associated with naturalistic fluctuations in estrogens and progesterone over the course of the menstrual cycle. Using a dynamic emotion recognition task we aimed to provide a comprehensive description of the association between ovarian hormone levels and emotion recognition performance using a variety of performance metrics. Naturally cycling, psychiatrically healthy women attended a single experimental session during a follicular (days 7-13; n = 16), early luteal (days 15-19; n = 14) or late luteal phase (days 22-27; n = 14) of their menstrual cycle. Correct responses and reaction times to dynamic facial expressions were recorded and a two-high threshold analysis was used to assess discrimination and response bias. Salivary progesterone and estradiol were assayed and subjective measures of premenstrual symptoms, anxiety and positive and negative affect assessed. There was no interaction between cycle phase (follicular, early luteal, late luteal) and facial expression (sad, happy, fearful, angry, neutral and disgusted) on any of the recognition performance metrics. However, across the sample as a whole, progesterone levels were positively correlated with reaction times to a variety of facial expressions (anger, happiness, sadness and neutral expressions). In contrast, estradiol levels were specifically correlated with disgust processing on three performance indices (correct responses, response bias and discrimination). Premenstrual symptoms, anxiety and positive and negative affect were not associated with emotion recognition indices or hormone levels. The study highlights the role of naturalistic variations in ovarian hormone levels in modulating emotion recognition. In particular, progesterone seems to have a general slowing effect on facial expression processing. Our findings also provide the first behavioural evidence of a specific role for estrogens in the processing of disgust in humans.
Project description:Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females' mid-luteal phase when progesterone and estradiol are highest, and early follicular phase when progesterone and estradiol are lowest. Significantly higher (?5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modeling, these changes were linked to stronger self-inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition, the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma-band oscillations.
Project description:Prepulse inhibition (PPI) of the startle response is sensitive to sex, with healthy young women showing less PPI compared with age-matched men, and varies according to the menstrual cycle phase in women. Relatively less is known regarding sex and hormonal influences in prepulse facilitation (PPF). Menstrual phase-related variability in PPI is suggested to be mediated by fluctuating estrogen level, based on the observations of more PPI in women during the follicular, relative to the luteal, phase. No study has directly assessed the relationship between fluctuating hormones and PPI or PPF levels over the human ovarian cycle. To examine the roles of circulating ovarian hormones in PPI and PPF, 16 non-smoking regularly menstruating healthy women were tested during both the follicular and luteal phases on PPI and PPF and provided saliva samples for measurement of 17beta-estradiol (estrogen), progesterone and testosterone. The results showed higher levels of 17beta-estradiol and progesterone during the luteal, relative to the follicular, phase; and more PPI during the follicular phase and more PPF during the luteal phase with comparable startle amplitude and habituation during the two phases. A larger increase in progesterone was associated with a smaller decrease in PPI from the follicular to the luteal phase. No significant associations were found between changes in PPI/PPF and estrogen levels. The findings confirm lower PPI during the luteal, compared with the follicular, phase and suggest a role for progesterone, more specifically an antipsychotic-like PPI-restoration action of progesterone, during the luteal phase in PPI of young women.
Project description: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.
Project description:The immune responses exhibited by females are distinct from those of males. Females are known to generate, among others, higher levels of antibodies, greater interferon responses, and increased levels of inflammatory mediators in response to pathogens. Mounting evidence suggests that gonadal hormones play a key role in these differences. To better understand the effect of cycling hormones on the immune response, we sought to investigate the relationship between gonadal hormone fluctuations during the ovarian cycle and the levels of interleukin 1? and IL-1RA, both in circulation and in PBMCs in response to TLR4 stimulation, in healthy premenopausal females. To do this we measured the gonadal hormones 17?-estradiol, progesterone, and luteinizing hormone, and the cytokines IL-1? and IL-1RA in nine cycling females at several time points throughout one complete cycle. We evaluated 35 follicular, 17 ovulatory, and 44 luteal time points in our cohort and found a clear increase in serum levels of anti-inflammatory IL-1RA in the luteal phase, as compared to the follicular phase, and a positive correlation between both 17?-estradiol and progesterone and IL-RA. There was no difference in the serum levels of IL-1? and no difference in IL-1 ? or IL-1RA produced in response to LPS by PBMCs isolated from different phases. Division of the cycle into sub-phases revealed an increase in the level of IL-1RA by ovulation that persisted through the luteal phase. These data suggest that significant changes in the immune response occur throughout the ovarian cycle in healthy females.
Project description:About 10% of Japanese female athletes are afflicted by menstrually-related edema, mainly in the lower limbs, and, with few studies on this problem, the effect on performance remains unclear.To quantitatively evaluate fluid retention in the calf in female students over their menstrual cycle using magnetic resonance imaging (MRI) and to determine the relationship of MRI changes and athletic performance.The menstrual cycle was divided into 5 phases: menstrual, follicular, ovulatory, early luteal, and late luteal with sampling done in either morning (AM) or afternoon (PM) sessions. At each phase, MRI of the calf (7:00-8:00, 14:00-16:00), body composition and hormones (7:00-8:00), and athletic performance (14:00-16:00) were evaluated.13 adult healthy Japanese female students with eumenorrhea.Estradiol levels decreased significantly in the menstrual phase and the follicular phase compared to the early luteal phase (P = 0.001, P = 0.024 respectively). Menstrual phase estradiol levels were significantly lower compared to the ovulatory phase (P = 0.015), and the late luteal phase (P = 0.003). Progesterone levels decreased significantly in the menstrual phase and the follicular phase compared to the ovulatory phase (P = 0.012, P = 0.009 respectively), the early luteal phase (both P = 0.007), and the late luteal phase (P = 0.028, P = 0.029 respectively), and it along with a significant decrease in the ovulatory phase compared to the early luteal phase (P = 0.010). AM T2 signals were significantly lower in the menstrual phase compared to the ovulatory phase (P = 0.043) but not other phases. PM T2 signals increased significantly in the menstrual phase compared to the follicular phase (P = 0.003), ovulatory phase (P = 0.009), and the late luteal phase (P = 0.032), and the difference between the AM and PM values increased significantly in the menstrual phase compared to the other 4 phases (P<0.01). A negative correlation between fluid retention and agility was observed.In female students fluid retention during the menstrual phase could be a factor that influences athletic agility.
Project description:We previously reported that BRCA1/2-mutated fallopian tube epithelium (FTE) collected during the luteal phase exhibits gene expression profiles more closely resembling that of high-grade serous carcinoma (HGSC) specimens than FTE collected during the follicular phase or from control patients. Since the luteal phase is characterised by high levels of progesterone, we determined whether the expression of progesterone receptor (PR) and PR-responsive genes was altered in FTE obtained from BRCA mutation carriers during the luteal phase of the menstrual cycle. RT-qPCR confirmed a decreased expression of PR mRNA in FTE during the luteal phase relative to follicular phase, in both BRCA1/2 mutation carriers and control patients. Immunohistochemistry using isoform-specific antibodies confirmed a low level of both PR-A and PR-B in HGSC and a lower level of staining in FTE samples obtained during the luteal phase compared with the follicular phase. No significant difference in PR-A or PR-B staining was found based on patient BRCA mutation status. Analysis of our previously reported gene expression profiles based upon known PR-A- and PR-B-specific target genes did not partition samples by BRCA mutation status, indicating that overall FTE PR response is not altered in BRCA mutation carriers. HGSC samples grouped separately from other samples, consistent with the observed loss of PR expression. These findings indicate no overall difference in PR signalling in FTE as a function of BRCA mutation status. Thus, the molecular similarity of BRCA1/2-mutated luteal phase FTE and HGSC likely results from an altered response to luteal phase factors other than progesterone.
Project description:Women report greater sleep disturbance during the premenstrual phase of the menstrual cycle and during menses. However, the putative hormonal basis of perceived menstrual cycle-related sleep disturbance has not been investigated directly. We examined associations of objective measures of sleep fragmentation with reproductive hormone levels in healthy, premenopausal women.Twenty-seven women with monthly menses had hormone levels measured at two time points during a single menstrual cycle: the follicular phase and the peri-ovulatory to mid-luteal phase. A single night of home polysomnography (PSG) was recorded on the day of the peri-ovulatory/mid-luteal-phase blood draw. Serum progesterone, estradiol, and estrone levels concurrent with PSG and rate of change in progesterone (PROGslope) from the follicular blood draw to PSG were correlated with log-transformed wake after sleep onset (lnWASO%) and number of wakes/hour of sleep (lnWake-Index) using linear regression.Sleep was more fragmented in association with a steeper PROGslope (lnWASO% p=0.016; lnWake-Index p=0.08) and higher concurrent estrone level (lnWASO% p=0.03; lnWake-Index p=0.01), but the effect of estrone on WASO was lost after accounting for PROGslope. WASO% and Wake-Index were not associated with concomitant progesterone or estradiol levels.A steeper rate of rise in progesterone levels from the follicular phase through the mid-luteal phase was associated with significantly greater WASO, establishing a link between reproductive hormone dynamics and sleep fragmentation in the luteal phase of the menstrual cycle.
Project description:Hormonal transitions across the menstrual cycle may modulate human reward processing and reinforcement learning, but previous results were contradictory. Studies assessed relatively small samples (n < 30) and exclusively used within-subject designs to compare women in hormonally distinct menstrual cycle phases. This increased the risk of sporadic findings and results may have been disproportionally affected by expectancy effects. Also, replication studies are widely missing, which currently precludes any reliable inferences. The present study was intended as a conceptual replication of a previous study [(1), Neuropsychologia 84; n = 15]. There, we had observed a reduction in avoidance learning capacity when women were in the high estradiol state of the late follicular phase as compared to the mid luteal phase with enhanced progesterone influence. These results conformed to the idea that estradiol and progesterone may antagonistically modulate dopaminergic transmission as a dopamine agonist and antagonist, respectively. Heightened progesterone in the luteal phase thereby supported the ability to learn from the negative outcomes of one's actions, while the follicular rise in estradiol interfered with this capacity. Here, we re-examined the above described within-subject difference between the follicular and the luteal phase in a between-subjects design. Seventy-five women were tested once with a probabilistic feedback learning task, while being either in the follicular (36 women) or luteal phase (39 women), and were compared for phase-related differences in behavior. Secondly, we combined the new data with data from three previous studies from our laboratory that used the same task and menstrual cycle phases. This meta-analysis included only data from the first test day, free of any biasing expectancy effects. Both analyses demonstrated the consistency of the decline in avoidance learning in the follicular relative to the luteal phase. We also showed that this decline reliably occurred in all of the included samples. Altogether, these results provide evidence for the consistency of a behavioral difference and its apparent association with a transient change in hormonal state that occurs in the natural menstrual cycle. Our findings may also open new avenues for the development of reliable between-subjects test protocols in menstrual cycle research.