Influence Of Menstrual Cycle Phase Research Articles

Injury Incidence, Severity, and Type Across the Menstrual Cycle in Female Footballers: A Prospective Three Season Cohort Study.

The aim of the study was to assess the influence of menstrual cycle phase on injury incidence, severity, and type in elite female professional footballers over three seasons. Time-loss injuries and menstrual cycle data were prospectively recorded for 26 elite female football players across three seasons. The menstrual cycle was categorized into four phases using a standardized model: menstruation (phase 1; P1), remainder of follicular phase (phase 2; P2), early luteal (phase 3; P3), and premenstrual phase (phase 4; P4). Injury incidence rates (IIR) and ratios (IIRR) were calculated for overall injuries, injury severity, type, contact vs noncontact, and game/training. A total of 593 cycles across 13,390 d were tracked during the study, and 74 injuries from 26 players were eligible for analysis. When comparing IIR between phases (reference: P1), overall injury rates were highest in P4 (IIRR, 2.30 (95% confidence interval, 0.99-5.34; P = 0.05)). When examining rates by injury severity and type, IIR values were also highest in P4 for ≤7 d' time-loss (4.40 (0.93-20.76; P = 0.06)), muscle-specific (6.07 (1.34-27.43; P = 0.02)), and noncontact (3.05 (1.10-8.50; P = 0.03)) injuries. Muscle-specific (IIRR P3/P1, 5.07 (1.16-22.07; P = 0.03)) and ≤7 d' time-loss (4.47 (1.01-19.68; P = 0.05)) injury risk was also significantly higher in P3. Muscle injuries were the most prevalent subtype ( n = 41). No anterior cruciate ligament injuries were recorded across the monitoring period. Injury risk was significantly elevated during the luteal phase of the menstrual cycle (P3 and P4) among elite female professional footballers. Further research is urgently needed to better understand the influence of the menstrual cycle on injury risk and to develop interventions to mitigate risk.

Influence of menstrual cycle phase and oral contraceptive phase on exercise performance in endurance-trained females.

Limited data exists on the influence of menstrual cycle (MC) phase and oral contraceptive (OC) phase on physical performance in endurance-trained females due to poor control regarding MC verification and differentiation. We aimed to evaluate exercise performance and the respiratory response to exercise in three distinct phases of the MC and OC cycle in endurance-trained females. Using a prospective cohort study design, we recruited trained females (Vo<inf>2max</inf> 52±4 mL O<inf>2</inf>/min/kg) who were either not using oral contraceptives (NOC) or using monophasic OCs. NOC were tested in the early and late follicular phase (FP) and the mid-luteal phase (LP). OC-users were tested in the withdrawal phase (WP) and two times in the active OC phase (OCP). The test battery included DXA scans, blood sampling, a submaximal bike test, a maximal isometric knee-extensor strength test, 4 and 20-second bike sprints, and a 6 min time trial on a bike. MC phases were verified by the use of ovulation kits and circulating sex hormone levels. After the exclusion of four NOCs due to inadequate sex hormone levels, 11 NOC and 13 OC users were included in the final analysis. 6 min time trial performance, sprint performance, and most submaximal exercise intensity variables did not differ between MC phases and OC cycle phases. However, in NOC, ventilation (L/min) during exercise at 30% of aerobic peak power was 7.6% lower in the late FP compared to the LP (P<0.05). In OC users, muscle strength was 3.9% higher in the early OCP compared to WP (P<0.05), whereas body mass was higher in the late OCP compared to WP (P<0.05). Collectively, our study suggests that MC phase and OCP influence exercise performance to a limited extent in endurance-trained females.

The Influence of Menstrual-Cycle Phase on Measures of Recovery Status in Endurance Athletes: The Female Endurance Athlete Project.

To investigate the influence of menstrual-cycle (MC) phase on measures of recovery status, that is, resting heart rate, perceived sleep quality, and physical and mental readiness to train, among female endurance athletes. Daily data were recorded during 1 to 4 MCs (ie,duration ≥21 and ≤35d, ovulatory, luteal phase ≥10d) of 41 trained-to-elite-level female endurance athletes (mean [SD]: age 27 [8]y, weekly training: 9 [3]h). Resting heart rate was assessed daily using a standardized protocol, while perceived sleep quality and physical and mental readiness to train were assessed using a visual analog scale (1-10). Four MC phases (early follicular phase [EFP], late follicular phase, ovulatory phase, and midluteal phase [MLP]) were determined using the calendar-based counting method and urinary ovulation-prediction test. Data were analyzed using linear mixed-effects models. Resting heart rate was significantly higher in MLP (1.7beats·min-1, P = .006) compared with EFP without significant differences between the other MC phases. Perceived sleep quality was impaired in MLP compared with late follicular phase (-0.3, P = .035). Physical readiness to train was lower both in ovulatory phase (-0.6, P = .015) and MLP (-0.5, P = .026) compared with EFP. Mental readiness to train did not show any significant differences between MC phases (P > .05). Although significant, the findings had negligible to small effect sizes, indicating that MC phase is likely not the main determinant of changes in measures of recovery status but, rather, one of the many possible stressors.

Impact of aerobic fitness status, menstrual cycle phase, and oral contraceptive use on exercise substrate oxidation and metabolic flexibility in females.

The influence of menstrual cycle phase and fitness status on metabolism during high-intensity interval exercise (HIIE) was assessed. Twenty-five females (24.4 (3.6) years) were categorized by normal menstrual cycle (n=14) vs. oral contraceptive (OC) use (n=11) and by aerobic fitness, high-fitness females (HFF; n=13) vs. low-fitness females (LFF; n=12). HIIE was four sets of four repetitions with a 3min rest between intervals on a cycle ergometer at a power output halfway between the ventilatory threshold and V̇O2peak and performed during follicular (FOL: days 2-7 or inactive pills) and luteal phases (LUT: day ∼21 or 3rd week of active pills). Substrate oxidation was assessed via indirect calorimetry, blood lactate via finger stick, and recovery of skeletal muscle oxidative metabolism (mV̇O2) via continuous-wave near-infrared spectroscopy. HFF oxidized more fat (g·kg-1) during the full session (FOL: p=0.050, LUT: p=0.001), high intervals (FOL: p=0.048, LUT: p=0.001), low intervals (FOL: p=0.032, LUT: p=0.024), and LUT recovery (p=0.033). Carbohydrate oxidation area under the curve was greater in HFF during FOL (FOL: p=0.049, LUT: p=0.124). Blood lactate was lower in LFF in FOL (p≤0.05) but not in LUT. Metabolic flexibility (Δ fat oxidation g·kg-1·min-1) was greater in HFF than LFF during intervals 2-3 in FOL and 1-4 in LUT (p≤0.05). Fitness status more positively influences exercise metabolic flexibility during HIIE than cycle phase or OC use.

Current evidence shows no influence of women's menstrual cycle phase on acute strength performance or adaptations to resistance exercise training.

The bias towards excluding women from exercise science research is often due to the assumption that cyclical fluctuations in reproductive hormones influence resistance exercise performance and exercise-induced adaptations. Hence, the purpose of this umbrella review was to examine and critically evaluate the evidence from meta-analyses and systematic reviews on the influence of menstrual cycle phase on acute performance and chronic adaptations to resistance exercise training (RET). We observed highly variable findings among the published reviews on the ostensible effects of female sex hormones on relevant RET-induced outcomes, including strength, exercise performance, and hypertrophy. We highlight the importance of comprehensive menstrual cycle verification methods, as we noted a pattern of poor and inconsistent methodological practices in the literature. In our opinion, it is premature to conclude that short-term fluctuations in reproductive hormones appreciably influence acute exercise performance or longer-term strength or hypertrophic adaptations to RET.

Protein Requirements of Pre-Menopausal Female Athletes: Systematic Literature Review.

This systematic literature review aimed to determine the protein requirements of pre-menopausal (e.g., 18–45 years) female athletes and identify if the menstrual cycle phase and/or hormonal contraceptive use influence protein requirements. Four databases were searched for original research containing pre-menopausal female athletes that ingested protein alongside exercise. The Academy of Nutrition and Dietetics Quality Criteria Checklist was used to determine study quality. Fourteen studies, which included 204 recreationally active or competitive females, met the eligibility criteria for inclusion in this review, and all were assessed as positive quality. The estimated average requirement (EAR) for protein intake of pre-menopausal recreational and/or competitive female athletes is similar for those undertaking aerobic endurance (1.28–1.63 g/kg/day), resistance (1.49 g/kg/day) and intermittent exercise (1.41 g/kg/day) of ~60–90 min duration. The optimal acute protein intake and influence of menstrual cycle phase or hormonal contraceptive use on protein requirements could not be determined. However, pre- and post-exercise protein intakes of 0.32–0.38 g/kg have demonstrated beneficial physiological responses in recreational and competitive female athletes completing resistance and intermittent exercise. The protein requirements outlined in this review can be used for planning and assessing protein intakes of recreational and competitive pre-menopausal female athletes.

A 10-Week Block of Combined High-Intensity Endurance and Strength Training Produced Similar Changes in Dynamic Strength, Body Composition, and Serum Hormones in Women and Men.

Purpose: To examine the potential sex differences in adaptations to combined endurance and strength training in recreationally endurance trained (eumenorrheic) women (n = 9) and men (n = 10).Methods: Isometric (ISOMmax) and dynamic bilateral leg press (1RM), countermovement jump (CMJ), running performance (3,000 m time trial), lean mass and body fat % (LEAN and FAT% determined by dual X-ray absorptiometry) as well as serum testosterone and cortisol (TES and COR, respectively, measured using hormone-specific immunoassay kits) were examined before a control period and pre, mid, and post a supervised 10-week combined high-intensity interval endurance training (4 × 4 min intervals and 3 × 3 × 100 m repeated sprints) and mixed maximal and explosive strength training. No more than 2 weeks separated training and testing for either women or men and all women were tested in the early follicular phase of the menstrual cycle to minimize the possible influence of menstrual cycle phase on performance measures.Results: Absolute and relative changes in 1RM, CMJ, 3,000 m, LEAN, and FAT% were similar between groups. The only statistically significant differences observed between groups were observed at post and included a larger Δ% increase in ISOMmax force in men and a relatively greater Δ% decrease in serum TES in women.Conclusion: Women and men can achieve similar relative adaptations in dynamic maximal strength and CMJ as well as endurance performance gains and body composition over the same high-intensity 10-week combined program, although relative adaptations in TES may differ.

Effect of menstrual cycle on resting metabolism: A systematic review and meta-analysis.

BackgroundThe need to control for the potential influence of menstrual cycle phase on resting metabolism (RMR) places a burden on research participants who must self-report onset of menstruation and researchers who must schedule metabolic testing accordingly.PurposeTo systematically review and analyze existing research to determine the effect of menstrual cycle on RMR.MethodsWe searched PubMed, CINAHL, MEDLINE, SPORTDiscus, and Scopus databases using the search terms “menstrual cycle and metabolic rate” and “menstrual cycle and energy expenditure.” Eligibility criteria were English language, single-group repeated measures design, and RMR as either a primary or secondary outcome. Risk of bias was assessed based on study sample, measurement, and control of confounders. Differences between the follicular and luteal phases of the menstrual cycle were analyzed using the standardized mean difference in effect size.ResultsThirty English-language studies published between 1930 and December 2019 were included in the systematic review, and 26 studies involving 318 women were included in the meta-analysis. Overall, there was a small but significant effect favoring increased RMR in the luteal phase (ES = 0.33; 95% CI = 0.17, 0.49, p < 0.001).DiscussionLimitations include risk of bias regarding measurement of both menstrual cycle and RMR. Sample sizes were small and studies did not report control of potential confounders. Sub-group analysis demonstrated that in more recent studies published since 2000, the effect of menstrual phase was reduced and not statistically significant (ES = 0.23; 95% CI = -0.00, 0.47; p = 0.055). Until larger and better designed studies are available, based on our current findings, researchers should be aware of the potential confounding influence of the menstrual cycle and control for it by testing consistently in one phase of the cycle when measuring RMR in pre-menopausal women.

The impact of menstrual-cycle phase on basal and exercise-induced hormones, mood, anxiety and exercise performance in physically active women.

The influence of menstrual cycle phase on perceptual responses and exercise performance is still unclear in the literature. Therefore, this study investigated salivary estradiol (sal-E<inf>2</inf>) and cortisol (sal-C) concentrations, mood, anxiety and exercise (aerobic, anaerobic) performance in physically-active women across two menstrual-cycle phases. Twelve women (mean age 24.9±4.3 years) were assessed in the early follicular (early-FP) and mid luteal (mid-LP) phase of their menstrual cycle. In each phase, participants were tested for both aerobic (i.e. VO<inf>2max</inf>) and anaerobic (i.e. peak power, average power and Fatigue Index) performance. Basal and exercise-induced changes in sal-E<inf>2</inf> and sal-C concentrations, self-appraised mood and anxiety were assessed. We observed a significant increase in basal (pre-exercise) sal-E<inf>2</inf> concentration from early-FP to mid-LP (P≤0.05), coupled with a significant increase in VO<inf>2max</inf> in early-FP (39.9±7.8 mL/kg/min) versus mid-LP (36.9±7.8 mL/kg/min). Depression also decreased with aerobic exercise, but only in the early-FP. No other significant menstrual-phase differences in exercise performance, emotional state or hormonal change scores were identified. Our data suggest that physically-active women may experience a natural rise in estradiol concentration, as they transition from the early-FP to mid-LP. In the present study, this was accompanied by a small reduction in VO<inf>2max</inf>. An exercise (aerobic)-related decline in depression also emerged in the early-FP. Most of the exercise performance, emotional state and hormonal measures did not exhibit any menstrual phase-related difference.

Blood Plasma Hormone-Level Influence on Vocal Function.

Purpose This preliminary study examined the influence of menstrual cycle phase and hormone levels on acoustic measurements of vocal function in reproductive and postmenopausal females. Mean fundamental frequency (f0), speaking fundamental frequency (Sf0), and cepstral peak prominence (CPP) were evaluated. It was hypothesized that Sf0 and CPP would be lower during the luteal and ischemic phases of the menstrual cycle. Group differences with lower values in postmenopausal females and greater variability in the reproductive females were also hypothesized. Method A mixed factorial analysis of variance was used to examine differences between reproductive and postmenopausal females and the four phases of the menstrual cycle. Separate analyses of variances were implemented for each of the dependent measures. Twenty-eight female participants (15 reproductive cycling, 13 postmenopausal) completed the study. Participants were recorded reading the Rainbow Passage and sustaining the vowel /a/. Mean vocal f0, Sf0, and CPP were determined from the acoustic samples. Blood assays were used to determine estrogen, progesterone, testosterone, and neuropeptide Y levels at four data collection time points. Results Group differences in hormone levels and Sf0 values were established with the postmenopausal group having significantly lower hormone levels and significantly lower Sf0 than the reproductive cycling group across the phases. Analysis of the reproductive group by hormone levels and cycle phase revealed no significant differences for CPP or Sf0 across phases. Higher estrogen was identified in the ovulation phase, and higher progesterone was identified in the luteal phase. Conclusions Significant differences in hormone levels and Sf0 were identified between groups. Within the reproductive cycling group, the lack of significant difference in acoustic measures relative to hormone levels indicated that the measures taken may not have been sensitive enough to identify hormonally mediated vocal function changes. The participant selection may have biased the findings in that health conditions and medications that are known to influence voice function were used as exclusion criteria.

Influence of Menstrual Cycle Phase on Cardiovascular Drift and Maximal Oxygen Uptake During Heat Stress

Influence of Menstrual Cycle Phase on Cardiovascular Drift and Maximal Oxygen Uptake During Heat Stress

Physiological Responses of Male and Female Race Car Drivers during Competition.

1) To evaluate the physiological responses of male and female drivers in open and closed cockpit race cars, 2) to examine the moderating influence of menstrual cycle phase on physiological responses to racing among female drivers. HR, breathing rate, skin temperature, core temperature, and Physiological Strain Index (PSI) were measured using the Equivital Life Monitor in male (n = 6) and female (n = 6) drivers at three races in open or closed cockpit cars. Among females, menstrual cycle phase for each race was recorded. During racing conditions there was no difference (P > 0.05) between male and female drivers for HR, skin temperature, core temperature, or PSI. The female drivers had a higher (P < 0.001) breathing rate compared with the male drivers. Compared with the follicular phase, the luteal phase had an increased (P < 0.001) HR, breathing rate, skin temperature, core temperature, and PSI. The closed cockpit cars elicited (P < 0.001) a higher skin temperature, core temperature and PSI as compared with the open cockpit cars. There were no differences in the physiological responses to automobile racing between male and female drivers. The luteal phase elicited higher physiological responses than the follicular phase, but was not different from the male drivers. Thereby, practitioners should focus on reducing stresses induced by a closed cockpit race car as opposed to the menstrual cycle.

Effect of menstrual cycle on ethanol drinking in rhesus monkeys

BackgroundSex differences in the abuse-related effects of alcohol have been demonstrated in the clinic and in preclinical animal models. Less is known about the influence of menstrual cycle phase on drinking. MethodsIn this study, we examined the relationship between menstrual cycle phase and intake of ethanol (EtOH) in five adult female rhesus monkeys. Subjects consumed a 4% EtOH solution in their home cage 6 h per day, 5 days per week and pressed a lever to receive food pellets during the drinking session. Menstrual cycle was determined with vaginal swabs 5–7 days per week. To facilitate comparison with previous studies, the cycle was divided three different ways for analysis. ResultsFirst, no significant difference was observed when EtOH intake was compared between phases defined as “follicular” (days 5–10) and “luteal” (19–24). Second, when the cycle was further divided into four phases [early follicular (days 1–7), late follicular (8–14), early luteal (15–21) and late luteal (22-next cycle)], significant differences were detected, with intake highest in phases that bracket menses and lowest in the late follicular phase. Finally, EtOH intake during “mid-cycle” (days 12–16) was significantly lower than during “menses” (days 1–5) and “late luteal” (last 5 days). Effect sizes were small to moderate, although absolute differences in EtOH intake (g/kg) were <15%. Food-maintained responding was not different across phases. ConclusionsMenstrual cycle has modest but statistically significant and selective effects on EtOH drinking, with higher EtOH intake observed in the peri-menstrual period compared to the middle of the cycle.

Sex differences and functional hemispheric asymmetries during number comparison

BackgroundGlobal-local stimuli are hierarchical structures consisting of a larger global structure which is composed of smaller local stimuli. Numbers are also constructed hierarchically, with multi-digit numbers being made up from single digits. During two-digit number comparison, compatible items (larger number contains larger unit digit, e.g., 53 vs. 68) are processed faster and more accurately than incompatible items (smaller number contains larger unit digit, e.g., 58 vs. 63). This so-called unit-decade-compatibility effect has challenged the holistic model of number processing and suggests that the processing of number magnitudes occurs at least in part, decomposed, i.e., separately for each digit. Thus, the compatibility effect is indicative of how decomposed numbers are processed, thereby sharing similarities with traditional global-local processing of hierarchical stimuli.The goal of this study was to investigate whether factors that have been shown to reliably influence global-local processing also affect the compatibility effect during number comparison. Those include visual hemifield, sex, and menstrual cycle phase in women.MethodOne hundred sixty participants, 77 naturally cycling women and 83 men, completed a two-digit number comparison task twice, with test-sessions time-locked to the early follicular or mid-luteal cycle phase in women. Number comparison stimuli were presented to the right or left hemifield, respectively.ResultsWe observed a stronger compatibility effect in the right visual hemifield compared to left visual hemifield and in women compared to men, but no evidence for an influence of menstrual cycle phase in women could be found.ConclusionHemispheric asymmetries in holistic versus decomposed number processing could be demonstrated for the first time, suggesting a similar hemispheric modulation for number magnitude processing as for global-local processing.

Oral Contraceptive Pill Alters Acute Dietary Protein-Induced Thermogenesis in Young Women.

There is much interest in the role of dietary protein for weight control. However, there remains a need to characterize individual determinants of the thermogenic effects of protein. This study aimed to investigate the influence of menstrual cycle phase and the combined, monophasic oral contraceptive pill on the thermogenic response to a standardized high-protein (HP) versus normal-protein (NP) meal. Following an overnight fast, resting energy expenditure (EE) was measured in 16 healthy young women (8 taking and 8 not taking the pill) and 8 men for 30 minutes pre ingestion and 3 hours post ingestion of a NP (11%) or HP (24%) meal. There was no effect of menstrual phase or contraceptive pill use on fasting EE or NP response. However, HP increased EE significantly more than NP in women not taking the oral contraceptive pill and in men, but not in women taking the pill. This study shows an absence of the greater thermic effect of HP versus NP in women taking the oral contraceptive pill and has important implications regarding the effectiveness of HP for body weight regulation in women. With current obesity treatment/prevention strategies remaining largely ineffective, understanding the relationship between oral contraceptive pill use and protein-induced thermogenesis may enable the successful recalibration of existing dietary recommendations.

Heterogeneous Circulating Angiogenic Cell Responses to Acute Maximal Exercise.

Circulating angiogenic cells (CAC) comprise multiple subpopulations of exercise-inducible peripheral blood mononuclear cells (PBMC) that promote angiogenesis and maintain endothelial integrity. We examined the effect of acute maximal exercise on CD31, CD62E, CD14/CD31, CD34/VEGFR2, CD3/CD31, and CD3 PBMC in young, healthy adults. Blood samples were collected before and immediately after a graded treadmill exercise test for CAC analysis via flow cytometry. Maximal exercised produced 40%, 29%, 33%, 14%, and 33% increases in lymphocytic CD31, monolymphocytic CD31, CD62E, CD14/CD31, and CD34/VEGFR2 PBMC, respectively (P < 0.05). CD3/CD31 and CD3 cells were not altered with exercise. CD62E and CD14/CD31 PBMC were selectively augmented in women by 54% and 20%, respectively (P < 0.05). Exploratory analyses indicated that maximal exercise induced greater increases in CD62E and CD14/CD31 PBMC among women in the luteal phase compared with those in the follicular phase (P < 0.05). Basal lymphocytic PBMC and postexercise lymphocytic and monolymphocytic CD31 PBMC were lower among contraceptive users than nonusers. Maximal exercise induces a robust CAC response encompassing both progenitor and nonprogenitor cell types, with these effects differing between men and women for CD62E and CD14/CD31 cell types and the potential influence of menstrual cycle phase and contraceptive use.

Influence of menstrual cycle phase on resting-state functional connectivity in naturally cycling, cigarette-dependent women.

BackgroundSex differences in tobacco-related morbidity and mortality exist, with women experiencing more severe health consequences and greater difficulty with smoking cessation than men. One factor that likely contributes to these sex differences is menstrual cycle phase and associated neural and cognitive changes associated with ovarian hormone fluctuations across the menstrual cycle. Previously, we showed that naturally cycling, cigarette-dependent women in the follicular phase of their menstrual cycle showed greater reward-related neural activity and greater craving during smoking cue exposure. To better understand our results and the observed sex differences in smoking behavior and relapse, we explored potential menstrual cycle phase differences in resting-state functional connectivity (rsFC) in naturally cycling, cigarette-dependent women. Understanding how menstrual cycle phase affects neural processes, cognition, and behavior is a critical step in developing more efficacious treatments and in selecting the best treatment option based on a patient’s needs.MethodsResting-state functional connectivity analyses were used to examine connectivity strength differences between naturally cycling, premenopausal, cigarette-dependent women who were in the follicular phase (FPs; n = 22) and those in the luteal phase (LPs, n = 16) of their menstrual cycle. We also explored associations between connectivity strength and attentional bias to smoking cues.ResultsCompared with LPs, FPs showed decreased rsFC between the dorsal anterior cingulate cortex (dACC) and the subgenual anterior cingulate cortex, medial orbitofrontal cortex (mOFC), and ventral striatum. Among FPs, rsFC strength between the dACC and the bilateral dorsolateral prefrontal cortex (DLPFC), the bilateral dorsal striatum, and the left temporal gyrus was inversely correlated with attentional bias to smoking cues.ConclusionsThis is the first study to explore menstrual cycle phase differences in rsFC among cigarette-dependent women, and results suggest that FPs show differences in rsFC underlying cognitive control, which could place them at greater risk for continued smoking and relapse. These findings provide new insights toward individualized treatment strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0078-6) contains supplementary material, which is available to authorized users.

Influence of menstrual cycle phase on neural and craving responses to appetitive smoking cues in naturally cycling females.

Functional magnetic resonance imaging (fMRI) has been used extensively in an attempt to understand brain vulnerabilities that mediate maladaptive responses to drug cues. Using perfusion fMRI, we have consistently shown reward-related activation (medial orbitofrontal cortex/ventral striatum) to smoking cues (SCs). Because preclinical and clinical studies generally show that progesterone may reduce reward and craving, we hypothesized that females in the follicular phase of the cycle (FPs; when progesterone levels are low) would have greater reward-related neural responses to SCs compared with females in the luteal phase (LPs). Sated cigarette-dependent premenopausal naturally cycling females underwent pseudo-continuous arterial spin-labeled perfusion fMRI during exposure to 10-min audio visual clips of appetitive SCs and non-SCs. Brain responses to SCs relative to non-SCs were examined among females grouped according to menstrual cycle (MC) phase at the time of scanning (22 FPs, 15 LPs). Craving scores were acquired pre- and post-SC exposure. FPs showed increased neural responses to SCs compared with non-SCs in the medial orbitofrontal cortex (p ≤ .05 corrected), whereas LPs did not. FPs reported SC-elicited craving (p ≤ .005), whereas LPs did not. Within FPs, SC-induced craving correlated with increased neural responses in the anterior insula (r = 0.73, p < .0001). FPs may be more vulnerable to relapse during appetitive SC exposure than LPs. Because the influence of MC phase on drug cue neural activity has not been examined, these results contribute to our knowledge of the neurobiological underpinnings of responses to drug cues, and they highlight the importance of monitoring menstrual cycle phase in all areas of addiction research.

Influence of menstrual cycle phase on the cerebrovascular response to hypoxia: role of cyclooxygenase (708.1)

Menstrual phases influence resting cerebral blood flow (CBF), partially through cyclooxygenase (COX) mediated signaling. It is unknown if menstrual cycle hormone variations influence the CBF response to hypoxic stress. Compared to early follicular phase, we hypothesized females in early luteal phase would exhibit a larger, COX‐dependent, hypoxia‐mediated increase in CBF. We measured middle cerebral artery velocity (MCAv) with transcranial Doppler ultrasound in 4 healthy females (22 ± 3 yrs). Cerebral vascular conductance index (CVCi = MCAv*100/MABP) was calculated to normalize for potential differences in blood pressure. Females were studied twice each in early follicular (cycle day 1‐5) and late luteal (cycle day 12‐16) phases of the menstrual cycle, with and without COX inhibition (100 mg oral Indomethacin, Indo). Arterial O2 (SaO2) was reduced to 80% for 5 minutes while clamping end‐tidal CO2. On average, estrogen was higher (188 vs. 55 pg ml‐1) and progesterone was similar (790 vs. 603 pg ml‐1) during early luteal phase. Menstrual phase had no effect on basal CVCi (p=0.67) or the decrease in basal CVCi with Indo (p=0.45). Hypoxia increased CVCi (∆CVCi = 12 ± 1 cm s‐1 mmHg‐1; p&lt;0.001), but the hypoxia‐induced ∆CVCi was not altered by menstrual phase (p=0.53) or Indo (p=0.873). These data suggest that menstrual phase does not alter basal or hypoxic CVCi and the role of COX is unchanged in either response.Grant Funding Source: NIH R01 HL105820 &amp; AHA PRE7390038

Autonomic regulation across phases of the menstrual cycle and sleep stages in women with premenstrual syndrome and healthy controls.

To investigate the influence of menstrual cycle phase and the presence of severe premenstrual symptoms on cardiac autonomic control during sleep, we performed heart rate variability (HRV) analysis during stable non-rapid eye movement (NREM) and REM sleep in 12 women with severe premenstrual syndrome and 14 controls in the mid-follicular, mid-luteal, and late-luteal phases of the menstrual cycle. Heart rate was higher, along with lower high frequency (HF) power, reflecting reduced vagal activity, and a higher ratio of low frequency (LF) to high frequency power, reflecting a shift to sympathetic dominance, in REM sleep compared with NREM sleep in both groups of women. Both groups of women had higher heart rate during NREM and REM sleep in the luteal phase recordings compared with the mid-follicular phase. HF power in REM sleep was lowest in the mid-luteal phase, when progesterone was highest, in both groups of women. The mid-luteal phase reduction in HF power was also evident in NREM sleep in control women but not in women with PMS, suggesting some impact of premenstrual syndrome on autonomic responses to the hormone environment of the mid-luteal phase. In addition, mid-luteal phase progesterone levels correlated positively with HF power and negatively with LF/HF ratio in control women in NREM sleep and with the LF/HF ratio during REM sleep in both groups of women. Our findings suggest the involvement of female reproductive steroids in cardiac autonomic control during sleep in women with and without premenstrual syndrome.