Early Follicular Research Articles

Effect of menstrual cycle phase on physiological responses in healthy women at rest and during submaximal exercise at high altitude.

As more women engage in high-altitude activities, understanding how ovarian hormone fluctuations affect their cardiorespiratory system is essential for optimizing acclimatization to these environments. This study investigates the effects of menstrual cycle (MC) phases on physiological responses at rest, during and after submaximal exercise, at high-altitude (barometric pressure 509 ± 6 mmHg; partial pressure of inspired oxygen 96 ± 1 mmHg; ambient temperature 21 ± 2°C and relative humidity 27 ± 4%) in 16 eumenorrheic women. Gas exchange, hemodynamic responses, heart rate variability and heart rate recovery (HRR) were monitored at low altitude, and then at 3375m on the Mont Blanc (following nocturnal exposure) during both the early-follicular (EF) and mid-luteal (ML) phases. Significant differences were observed between low and high-altitude in ventilation, heart rate and cardiac output. Resting ventilation (15.2 ± 1.9 vs. 13.2 ± 2.5L.min-1; p = 0.039) and tidal volume (812 ± 217 vs. 713 ± 190 mL; p = 0.027) were higher during EF than ML at high-altitude. These differences between EF and ML were no longer evident during exercise, with comparable responses in oxygen uptake kinetics, cycling efficiency and HRR. The MC had negligible effects on physiological responses to high-altitude. An individualized approach, tailored to each woman's specific responses to hypoxia across the MC, may be more beneficial in optimizing high-altitude sojourns than general guidelines.

The Effects of Inorganic Nitrate Supplementation on Muscular Power and Endurance Across the Menstrual Cycle.

Oral inorganic nitrate (NO3-) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power in males and females, although data in females is limited. Estrogen increases NO bioavailability and fluctuates throughout the menstrual cycle (MC), with low levels in the early follicular (EF) phase and peaking during the late follicular (LF) phase. The purpose of the present study was to examine the effects of NO3- supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance, and recovery from fatigue in healthy young females during the EF and LF phases of the MC. Ten eumenorrheic females were tested in a double-blinded, randomized, placebo-controlled design. Participants consumed ~13mmol NO3-, in the form of 140ml beetroot juice (BRJ), or an identical NO3--depleted placebo (PL), for ~5 days prior to visits and 2 hours prior to testing. Plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition (p < 0.05). While isokinetic peak power was unchanged, calculated maximal power (Pmax) and maximal velocity (Vmax) was significantly worsened in the BRJ treatment independent of the MC phase (p = 0.02 and 0.03, respectively). Muscular endurance, MVIC, and fatigue recovery were unaltered by BRJ or the MC. These data indicate that NO3- supplementation decreased maximal power and velocity in females and suggest that the benefits of NO3- supplementation previously found in males may not extend to young females.

The effects of the menstrual cycle on the physiological responses to exercise in eumenorrheic women at high-altitude

Introduction&#x0D; The acute mountain sickness (AMS) prevalence increases with altitude; i.e.,10-25% at 2,500 m and 50-85% at ~5,000 m (Bärtsch &amp; Swenson, 2013). Women are more likely affected by AMS than men (Richalet et al., 2012). AMS can affect exercise performance. However, the effects of the menstrual cycle (MC) on physiological responses to exercise and on tolerance to high-altitude (HA) remain underexplored. It has been reported that ovarian hormones stimulate ventilation in normoxic conditions (Saaresranta &amp; Polo, 2002). Early findings suggest that running economy is lower in the mid-luteal (ML) compared to the early-follicular (EF) phase in normoxia (Goldsmith &amp; Glaister, 2020). However, cycling efficiency at HA has not been explored yet. Thus, we investigated the effects of acute HA exposure on ventilatory responses at rest and during exercise in healthy females during two different phases of their MC.&#x0D; Methods&#x0D; Sixteen eumenorrheic women (age: 33 ± 7 yr; MC length: 27 ± 2 days; not taking any hormonal contraceptive) took part in this study. First, over a 6-month period, the participants’ MC were monitored using a calendar method. Then, they reached the Torino Hut (3,375 m) by cable car and spent one night at HA on two different MC phases; i.e., during the early-follicular (EF; MC day 4 ± 1) and the mid-luteal (ML; day 20 ± 2) phases. Each time, they underwent a submaximal (1.2 W/kg) test on a cycle ergometer ~17 h after arrival at HA. In addition to this, participants filled in two questionnaires, the Lake Louise AMS Score and the Groningen Sleep Quality Scale, ~16 h after arrival at HA.&#x0D; Results&#x0D; Resting ventilation was significantly higher during EF compared to ML (15.2 ± 1.9 vs. 13.2 ± 2.5 L/min, p = 0.039), while no differences were found for ventilation during exercise (53.9 ± 13.2 vs. 53.5 ± 13.4 L/min, p = 0.695), cycling efficiency (21.7 ± 0.0% vs. 19.8 ± 0.0%, p = 0.244), saturation at rest (92.4 ± 1.3 vs. 91.3 ± 3.2%, p = 0.142) and during exercise (87.2 ± 5.7 vs. 89.0 ± 4.0%, p = 0.528). Moreover, no differences in the Lake Louise AMS (2.2 ± 1.5 vs. 1.7 ± 1.5, p = 0.266) or Groningen (8.0 ± 3.3 vs. 7.5 ± 3.4, p = 0.668) scores were noted between the two MC phases.&#x0D; Discussion/Conclusion&#x0D; Despite a slightly higher resting ventilation during EF, when both oestrogens and progesterone are at their lowest levels, there were no differences in ventilatory responses to exercise and in AMS between the different phases of the MC. Consequently, there is currently very little evidence to aptly recommend a specific MC phase for mountaineering or any other HA activities (Burtscher et al., 2023). Further investigations are requested to assess whether other physiological responses to HA may be influenced by hormonal variations.&#x0D; References&#x0D; Bärtsch, P., &amp; Swenson, E. R. (2013). Acute high-altitude illnesses. New England Journal of Medicine, 368, 2294–2302. https://doi.org/10.1056/NEJMcp1214870&#x0D; Burtscher, J., Raberin, A., Brocherie, F., Malatesta, D., Manferdelli, G., Citherlet, T., Krumm, B., Bourdillon, N., Antero, J., Rasica, L., Burtscher, M. &amp; Millet, G. P. (2023). Recommendations for women in mountain sports and hypoxia training/conditioning. Sports Medicine. Advance online publication. https://doi.org/10.1007/s40279-023-01970-6&#x0D; Goldsmith, E., &amp; Glaister, M. (2020). The effect of the menstrual cycle on running economy. The Journal of Sports Medicine and Physical Fitness, 60(4), 610–617. https://doi.org/10.23736/s0022-4707.20.10229-9&#x0D; Richalet, J.-P., Larmignat, P., Poitrine, E., Letournel, M., &amp; Canouï-Poitrine, F. (2012). Physiological risk factors for severe high-altitude illness: A prospective cohort study. American Journal of Respiratory and Critical Care Medecine, 185(2), 192–198. https://doi.org/10.1164/rccm.201108-1396OC&#x0D; Saaresranta, T., &amp; Polo, O. (2002). Hormones and breathing. American College of Chest Physicians, 122(6), 2165–2182. https://doi.org/10.1378/chest.122.6.2165

17β-Estradiol Effects in Skeletal Muscle: A 31P MR Spectroscopic Imaging (MRSI) Study of Young Females during Early Follicular (EF) and Peri-Ovulation (PO) Phases

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p &lt; 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

The role of sex hormones, oral contraceptive use, and its parameters on visuospatial abilities, verbal fluency, and verbal memory

Sex hormones can cross the blood-brain barrier and access brain regions underlying higher-order cognition. Containing synthetic sex hormones, oral contraceptives (OC) have been found to modulate visuospatial and verbal abilities, though inconsistencies have been found in the literature. Among possible explanations, certain OC use parameters (progestin androgenicity, synthetic hormone levels, duration of use) have not received consistent consideration. Thus, the objectives were to (1) examine group differences between men, combined OC users, and naturally cycling women (NC women; not using OC) in visuospatial abilities, verbal fluency, and verbal memory and (2) investigate the contribution of endogenous and exogenous sex hormones on these effects. We also aimed to (3) identify OC use parameters relevant to cognitive outcomes. In total, 70 combined OC users, 53 early follicular (EF) women, 43 pre-ovulatory (PO) women, and 47 men underwent cognitive tests. Performance was compared based on hormonal milieus (OC, EF, PO, men) and OC users' contraceptive androgenicity (anti, low, high). Correlations between performance, hormone levels and OC use duration were also conducted. OC use dampened the sex difference that typically favors men in 3D visuospatial abilities, whereas its duration of use positively predicted verbal fluency. Androgenicity and hormone levels did not predict performance in any task. These results highlight the importance of considering OC use duration. Results also did not support a role for androgenicity in cognition. Importantly, combined OC use (including prolonged use) does not impair visuospatial, verbal, and memory functions in a healthy young sample.

The effects of inorganic nitrate supplementation on exercise economy and endurance capacity across the menstrual cycle.

Oral inorganic nitrate (NO3-) supplementation has been shown to increase bioavailable NO and provide potential ergogenic benefits in males; however, data in females is scarce. Estrogen is known to increase endogenous NO bioavailability and to fluctuate throughout the menstrual cycle (MC), being lowest in the early follicular (EF) phase and highest during the late follicular (LF) phase. This study examined the effects of oral NO3- supplementation on exercise economy, endurance capacity, and vascular health in young females across the MC. Ten normally menstruating females' MCs were tested in a double-blinded, randomized design during both the EF and LF phases of the MC. Participants consumed ∼13 mmol NO3-, in the form of 140 mL beetroot juice (BRJ) or an identical NO3--depleted placebo (PL) for ∼3 days before lab visits and 2 h before testing on lab visits. Plasma nitrate, nitrite, and estradiol were assessed, as was blood pressure and pulse wave velocity. Moderate-intensity exercise economy and severe intensity time to exhaustion (TTE) were tested on a cycle ergometer. As expected, plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition. Exercise economy was unaltered by BRJ or the MC, however TTE was significantly worsened by 48 s (∼10%) after BRJ supplementation (P = 0.04), but was not different across the MC with no interaction effects. In conclusion, NO3- supplementation did not affect exercise economy or vascular health and worsened aerobic endurance capacity (TTE), suggesting healthy females should proceed with caution when considering supplementation with BRJ.NEW & NOTEWORTHY Although inorganic nitrate (NO3-) supplementation has increased in popularity as a means of improving exercise performance, data in females at different phases of the menstrual cycle are lacking despite known interactions of estrogen with NO. This study revealed neither NO3- supplementation nor the menstrual cycle influenced exercise economy or vascular health in healthy young naturally menstruating females, while NO3- supplementation significantly worsened endurance capacity (10%) independent of the menstrual cycle phase.

Sex and menstrual cycle influence human spatial navigation strategies and performance

Which facets of human spatial navigation do sex and menstrual cycle influence? To answer this question, a cross-sectional online study of reproductive age women and men was conducted in which participants were asked to demonstrate and self-report their spatial navigation skills and strategies. Participants self-reported their sex and current menstrual phase [early follicular (EF), late follicular/periovulatory (PO), and mid/late luteal (ML)], and completed a series of questionnaires and tasks measuring self-reported navigation strategy use, topographical memory, cognitive map formation, face recognition, and path integration. We found that sex influenced self-reported use of cognitive map- and scene-based strategies, face recognition, and path integration. Menstrual phase moderated the influence of sex: compared to men, women had better face recognition and worse path integration, but only during the PO phase; PO women were also better at path integration in the presence of a landmark compared to EF + ML women and men. These findings provide evidence that human spatial navigation varies with the menstrual cycle and suggest that sensitivity of the entorhinal cortex and longitudinal axis of the hippocampus to differential hormonal effects may account for this variation.

The effects of sex and menstrual cycle phase on sympathetic action potential recruitment patterns during hypercapnic-hypoxic apnea.

Previously, we demonstrated that integrated muscle sympathetic nerve activity (MSNA) responses to acute chemoreflex stress were augmented during the early follicular (EF) phase of the menstrual cycle relative to both the midluteal (ML) phase and males. These differences were most pronounced in the amplitude component of MSNA, suggesting EF-driven increases in action potential (AP) recruitment in females. Therefore, we tested the hypothesis that neural recruitment, quantified as MSNA AP discharge patterns during acute chemoreflex stress, is potentiated during EF. We retrospectively analyzed MSNA data from 9 young males and 7 young females tested during the EF and ML phases at rest and during a voluntary end-inspiratory hypercapnic-hypoxic apnea. Sympathetic AP discharge patterns were analyzed using wavelet-based methodology. Apnea-driven increases in AP frequency and AP content per integrated burst were greater in EF relative to ML (APs/min: P=0.02; APs/burst: P=0.03) and to males (APs/min: P=0.04; APs/burst: P=0.02). The recruitment of new larger AP clusters was greater in EF than ML (P<0.01) but not different from males (P=0.50). Interestingly, we observed a positive association between the magnitude of change in the estrogen/progesterone ratio from EF to ML and the change in AP cluster recruitment, as both decreased from EF to ML (R2=0.82; P<0.01). This suggests that the enhanced progesterone dominance over estrogen during ML may blunt the recruitment of new larger APs. Overall, these data indicate that both sex and the menstrual cycle impact AP recruitment patterns in a manner which may be mediated, at least in part, by gonadal hormones.

Skeletal muscle regeneration at different phases of the menstrual cycle

INTRODUCTION: The effect of estrogen on muscle function and recovery from damage has been studied, but the effects of estrogen fluctuations during the menstrual cycle on muscle regeneration remain inconclusive. PURPOSE: The purpose of this study was to examine the effects of menstrual cycle phases on muscle regeneration after electrically stimulated muscle damage. We hypothesized that muscle damage during the late follicular (LF) phase results in better muscle regeneration as compared to muscle damage during the early follicular (EF) phase. METHODS: 23 premenopausal females (21.3±2 yrs) were recruited and split into two groups, EF and LF. After menstrual cycle tracking and phase confirmation, subjects underwent 200 electrically stimulated eccentric muscle contractions one week after providing a muscle biopsy. 7 days after inducing muscle damage, the subjects reported to give a final biopsy. Sections from muscle samples were stained for markers of laminin, dystrophin, satellite cells (SCs; Pax7), nuclei, total macrophages (CD68), and anti-inflammatory macrophages (CD206/CD68). Data for SCs, and %CD206+CD68+ cells are presented as mean±SD, and damaged fibers and CD206+CD68+ cells/fiber are presented as median±interquartile range. RESULTS: Electrical stimulation caused muscle fiber necrosis (0.005±0.018 damaged fiber/fiber, p=0.0002) as measured by the laminin-containing and dystrophin-deficient fibers. There was no difference between EF and LF groups for the number of damaged fibers (p=0.055) Muscle damage resulted in ~200% increase in the total number of CD68+ macrophages (p=0.008), and ~ 40% increase in the number of SCs (p=0.001) in both groups. However, there was no significant difference between EF and LF groups for the change in total macrophages per fiber (p=0.07) or SCs/fiber (p=0.25) in response to electrically stimulated muscle damage. Anti-inflammatory macrophages increased by about 104%±127 in EF and 240%±390 in LF group, but the difference between groups was not significant (p=0.39). A comparison of the proportion of anti-inflammatory macrophages per total macrophages before and one week after muscle damage did not show any time effect (p=0.25), which could indicate the regenerative and anti-inflammatory state of skeletal muscle one week after damage. CONCLUSION: Contrary to our hypothesis, our data indicate that skeletal muscle regeneration is not affected by different phases of the menstrual cycle. However, this finding is limited to only some of the markers of regeneration one week after muscle damage. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Menstrual phase influences cerebrovascular responsiveness in females but may not affect sex differences.

Background and aims: Sex differences in the rate and occurrence of cerebrovascular diseases (e.g., stroke) indicate a role for female sex hormones (i.e., oestrogen and progesterone) in cerebrovascular function and regulation. However, it remains unclear how cerebrovascular function differs between the sexes, and between distinct phases of the menstrual cycle. This study aimed to compare cerebrovascular-CO2 responsiveness in 1) females during the early follicular (EF), ovulatory (O) and mid-luteal (ML) phases of their menstrual cycle; and 2) males compared to females during phases of lower oestrogen (EF) and higher oestrogen (O). Methods: Eleven females (25 ± 5years) complete experimental sessions in the EF (n = 11), O (n = 9) and ML (n = 11) phases of the menstrual cycle. Nine males (22 ± 3years) completed two experimental sessions, approximately 2weeks apart for comparison to females. Middle and posterior cerebral artery velocity (MCAv, PCAv) was measured at rest, during two stages of hypercapnia (2% and 5% CO2 inhalation) and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 and 24mmHg). The linear slope of the cerebral blood velocity response to changes in end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness.. Results: In females, MCAv-CO2 responsiveness to hypocapnia was lower during EF (-.78 ± .45cm/s/mmHg) when compared to the O phase (-1.17 ± .52cm/s/mmHg; p < .05) and the ML phase (-1.30 ± .82; p < .05). MCAv-CO2 responsiveness to hypercapnia and hypo-to-hypercapnia, and PCAv-CO2 responsiveness across the CO2 range were similar between menstrual phases (p ≥ .20). MCAv-CO2 responsiveness to hypo-to hypercapnia was greater in females compared to males (3.12 ± .91cm/s/mmHg vs. 2.31 ± .46cm/s/mmHg; p = .03), irrespective of menstrual phase (EF or O). Conclusion: Females during O and ML phases have an enhanced vasoconstrictive capacity of the MCA compared to the EF phase. Additionally, biological sex differences can influence cerebrovascular-CO2 responsiveness, dependent on the insonated vessel.

Do Recreationally-Trained Women of Different Ages Perceive Symptoms of the Menstrual Cycle and Adjust Their Training According to Phases?

We aimed to investigate the effects of the menstrual cycle (MC) in recreationally trained women athletes, including their perception of training, if age affected their perception of MC symptoms, and if they adjusted their training according to phases of the MC which they would perceive as the best/worst phase to train in. Three hundred- and ten-women amateur athletes with regular MC replied to an online quiz about their perception and the effects of MC on training and how they adjusted training according to their MC. Women were classified into three age groups: 18-25 years-old (n = 108), 26-35 years-old (n = 135), and 36-45 years-old (n = 67). Despite a higher ratio of younger perceived symptoms and the influence of MC phases in training, the group varied their training according to MC phases the least (37%) compared to 26-35 (50%) and 36-45-year-olds (40.2%). Most of athletes perceived the late follicular phase (LF) as the best phase to train in (18-25 = 79.6%; 26-35 = 80.7%; 36-45 = 91%) and the worst phases were early follicular (EF) (54.6%; 58% and 46.2%), and late luteal (LL) (38%; 48% and 47.7%). Regardless of age, most women perceived MC symptoms, and women in the 26-35 group adjusted their training more according to MC phases.

Muscle Performance during the Menstrual Cycle Correlates with Psychological Well-Being, but Not Fluctuations in Sex Hormones.

ABSTRACTPurposeWe aimed to study variations in strength and power performance during the menstrual cycle (MC) in eumenorrheic young women and during the pill cycle in oral contraceptives (OC) users.MethodsForty healthy, normal-weight women between 18 and 35 yr (n = 30 eumenorrheic women; n = 10 OC users) completed this prospective cohort study. Seven to nine times during the MC/pill-cycle, the participants completed a physical performance test series, a questionnaire about psychological well-being, blood sampling, and determination of body mass. The physical tests included isometric handgrip strength, elbow flexor strength, countermovement jump (CMJ) height, and a 10-s Wingate bike test.ResultsNo direct correlation was observed between the variations in sex hormones and physical performance parameters. However, positive correlations were observed between physical performance outcomes and self-reported motivation, perception of own physical performance level, pleasure level, and arousal level. CMJ was 6% lower in the late luteal phase (LL) compared with the midluteal phase (ML) (P = 0.04). Wingate peak power was 3% lower in early follicular (EF) compared with the ML (P = 0.04). Furthermore, Wingate average power was 2%–5% lower in LL compared with all other MC phases. In line with these observations, physical pain was higher in EF and LL, and the pleasure level was lower in EF compared with the other MC phases. In OC users, we observed no variation in performance and self-reported parameters between the placebo-pill phase and the OC-pill phase.ConclusionsImpairments in CMJ and Wingate performance were observed at the end and start of MC compared with other MC phases, which were associated with lower psychological well-being, but not the sex hormone fluctuations.

Sex, pain, and the microbiome: The relationship between baseline gut microbiota composition, gender and somatic pain in healthy individuals

Background and AimRelative to men, women present with pain conditions more commonly. Although consistent differences exist between men and women in terms of physiological pain sensitivity, the underlying mechanisms are incompletely understood and yet could inform the development of effective sex specific treatments for pain. The gut microbiota can modulate nervous system functioning, including pain signaling pathways. We hypothesized that the gut microbiota and critical components of the gut-brain axis might influence electrical pain thresholds. Further, we hypothesized that sex, menstrual cycle, and hormonal contraceptive use might account for inter-sex differences in pain perception. MethodsHealthy, non-obese males (N = 15) and females (N = 16), (nine of whom were using hormonal contraceptives), were recruited. Male subjects were invited to undergo testing once, whereas females were invited three times across the menstrual cycle, based on self-reported early follicular (EF), late follicular (LF), or mid-luteal (ML) phase. On test days, electrical stimulation on the right ankle was performed; salivary cortisol levels were measured in the morning; levels of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), pro-inflammatory cytokines were assessed in plasma, and microbiota composition and short-chain fatty acids (SCFAs) levels were determined in fecal samples. ResultsWe observed that the pain tolerance threshold/pain sensation threshold (PTT/PST) ratio was significantly lesser in women than men, but not PST or PTT alone. Further, hormonal contraceptive use was associated with increased LBP levels (LF & ML phase), whilst sCD14 levels or inflammatory cytokines were not affected. Interestingly, in women, hormonal contraceptive use was associated with an increase in the relative abundance of Erysipelatoclostridium, and the relative abundances of certain bacterial genera correlated positively with pain sensation thresholds (Prevotella and Megasphera) during the LF phase and cortisol awakening response (Anaerofustis) during the ML phase. In comparison with men, women displayed overall stronger associations between i) SCFAs data, ii) cortisol data, iii) inflammatory cytokines and PTT and PST. Discussion and conclusionOur findings support the hypothesis that the gut microbiota may be one of the factors determining the physiological inter-sex differences in pain perception. Further research is needed to investigate the molecular mechanisms by which specific sex hormones and gut microbes modulate pain signaling pathways, but this study highlights the possibilities for innovative individual targeted therapies for pain management.

Fluid Balance is Unlikely Modified by the Menstrual Cycle when Ad Libitum Drinking is Permitted During Physical Work in the Heat

PurposeFederal and local entities provide recommendations aiming to limit dehydration during occupational heat stress. These recommendations are largely founded on the premise that during physical work in the heat humans under drink, which increases the likelihood of dehydration. Nearly all these studies have been conducted in men. The female menstrual cycle is characterized by fluctuations in estrogen and progesterone, such that elevations in these ovarian sex hormones may modify fluid regulation by both reducing urine output and promoting fluid intake. However, it is unknown if body fluid balance (i.e., both fluid intake and output) during occupationally relevant heat stress scenarios is altered across the menstrual cycle. Therefore, we tested the hypothesis that during physical work in the heat women will be more dehydrated during the early follicular (EF) phase (when ovarian sex hormones are low), compared to the late follicular (LF) and mid‐luteal (ML) phases of the menstrual cycle (when ovarian sex hormones are elevated).MethodsEight healthy, eumenorrheic, unacclimated women (26 ± 5 y) completed three trials consisting of 4 h (half a workday) exposure to 33.8 ± 0.8°C, 54 ± 1% relative humidity (WBGT = 28.3 ± 0.2°C, the average heat stress encountered in outdoor occupations) during the EF, LF, ML phases of their menstrual cycle. All visits were completed using a block‐randomized, crossover design. Each hour participants walked on a treadmill for 30 min at an intensity evoking a rate of metabolic heat production (Hprod) of ~430 W (the average Hprod for outdoor workers in the U.S.), while the work‐rest ratio is consistent with the NIOSH heat stress recommendations. Participants drank a cool (12 ± 1°C) flavor preferred non‐caloric sport drink (Gatorade Zero) ad libitum. Nude body weight was measured pre‐ and post‐ exposure, and percent changes in body weight loss (%BWL) were interpreted as an index of changes in total body water. Total fluid intake and urine output were also measured and sweat loss was estimated from changes in body weight corrected for fluid intake and urine loss. Rectal temperature is reported as a change from pre‐ to post‐ exposure. Data are presented as mean ± SD.ResultsChanges in rectal temperature did not differ between menstrual cycle phases (EF: 0.3 ± 0.2°C, LF: 0.5 ± 0.5°C, ML: 0.3 ± 0.3°C, p = 0.544). Sweat loss (EF: 2628 ± 1504 mL, LF: 2804 ± 1204 mL, ML: 2817 ± 1267 mL, p = 0.762) and urine output (EF: 864 ± 494 mL, LF: 955 ± 540 mL, ML: 925 ± 480 mL, p = 0.725) also did not differ between phases. Likewise, there were no differences in fluid intake between phases (EF: 1764 ± 1039 mL, LF: 1849 ± 694 mL, ML: 1892 ± 883 mL, p = 0.785). Thus, %BWL did not differ between phases (EF: ‐0.3 ± 0.7%, LF: ‐0.1 ± 0.7%, ML: ‐0.3 ± 0.8, p = 0.530) and %BWL did not statistically differ from zero (p ≥ 0.247).ConclusionWhen cool, flavor preferred fluids are freely accessible, fluid balance in women likely does not differ across three distinct phases of the menstrual cycle and thus, is unlikely to result in a net loss of body water during occupationally relevant heat stress scenarios.

Cerebral autoregulation across the menstrual cycle in eumenorrheic women.

There is emerging evidence that ovarian hormones play a significant role in the lower stroke incidence observed in pre‐menopausal women compared with men. However, the role of ovarian hormones in cerebrovascular regulation remains to be elucidated. We examined the blood pressure‐cerebral blood flow relationship (cerebral autoregulation) across the menstrual cycle in eumenorrheic women (n = 12; mean ± SD: age, 31 ± 7 years). Participants completed sit‐to‐stand and Valsalva maneuvers (VM, mouth pressure of 40 mmHg for 15 s) during the early follicular (EF), late follicular (LF), and mid‐luteal (ML) menstrual cycle phases, confirmed by serum measurement of progesterone and 17β‐estradiol. Middle cerebral artery blood velocity (MCAv), arterial blood pressure and partial pressure of end‐tidal carbon dioxide were measured. Cerebral autoregulation was assessed by transfer function analysis during spontaneous blood pressure oscillations, rate of regulation (RoR) during sit‐to‐stand maneuvers, and Tieck’s autoregulatory index during VM phases II and IV (AI‐II and AI‐IV, respectively). Resting mean MCAv (MCAvmean), blood pressure, and cerebral autoregulation were unchanged across the menstrual cycle (all p > 0.12). RoR tended to be different (EF, 0.25 ± 0.06; LF; 0.19 ± 0.04; ML, 0.18 ± 0.12 sec−1; p = 0.07) and demonstrated a negative relationship with 17β‐estradiol (R2 = 0.26, p = 0.02). No changes in AI‐II (EF, 1.95 ± 1.20; LF, 1.67 ± 0.77 and ML, 1.20 ± 0.55) or AI‐IV (EF, 1.35 ± 0.21; LF, 1.27 ± 0.26 and ML, 1.20 ± 0.2) were observed (p = 0.25 and 0.37, respectively). Although, a significant interaction effect (p = 0.02) was observed for the VM MCAvmean response. These data indicate that the menstrual cycle has limited impact on cerebrovascular autoregulation, but individual differences should be considered.

The Effect of Menstrual Cycle Phase on Neural Recruitment Patterns during Acute Chemoreflex Stress

We have shown previously that muscle sympathetic nerve activity (MSNA) responses to acute chemoreflex stress are augmented during the early follicular (EF) phase of the menstrual cycle relative to the midluteal (ML) phase in young healthy women. Interestingly, these differences were most pronounced in terms of MSNA burst amplitude, which may imply that neural recruitment strategies are affected by menstrual cycle phase. Therefore, the purpose of this retrospective analysis was to test the hypothesis that the recruitment of large action potential (AP) clusters occurs to a greater extent during the EF phase of the menstrual cycle compared with the ML phase. MSNA data (microneurography) from 7 young healthy women (aged 23±3 years; body mass index 23±3 kg/m2) were examined at rest and during a voluntary end‐inspiratory apnea which followed a rebreathing protocol to an end‐tidal PO2 of 65 Torr. These data were collected during the EF and ML phases. APs were identified from the filtered MSNA signal using a custom wavelet deconstruction approach which quantified AP firing frequencies (overall AP frequency and AP content per integrated burst). The identified APs were also binned in accordance to peak to peak amplitude to determine individual AP clusters (Scott’s rule). Resting AP frequency and AP content per MSNA burst were not different between menstrual cycle phases (APs/min: P=0.23; APs/burst: P=0.26). Similarly, the number of identified AP clusters at rest did not differ between the EF and ML phases (8±4 vs10±4 clusters; P=0.16). During apnea, changes in AP frequency and AP content per MSNA burst (i.e. expressed relative to baseline) were greater during the EF phase than the ML phase (ΔAPs/min: P=0.02; ΔAPs/burst: P=0.02). Similarly, apnea‐induced recruitment of new AP clusters (i.e. clusters which were not activated at baseline) was greater during the EF phase compared to the ML phase (ΔAP clusters: +6±8 vs+2±6 clusters; P=0.009). Taken together, these findings confirm that augmented integrated MSNA reactivity to chemoreflex stress during the EF phase of the menstrual cycle is mediated by a greater recruitment of latent subpopulations of larger sympathetic neurons relative to the ML phase. We speculate that the change in the gonadal hormone profile between EF (i.e. low estradiol, progesterone) and ML (i.e. elevated estradiol and progesterone) may be associated with centrally‐mediated alterations to neural outflow during chemoreflex stress, although further research is certainly required to address this hypothesis.

Impact of the Menstrual Cycle Phases on the Movement Patterns of Sub-Elite Women Soccer Players during Competitive Matches.

The purpose of this study was to evaluate the influence of the menstrual cycle phases on the movement patterns of sub-elite women soccer players during competitive matches over three consecutive seasons. Individual movement data were analyzed and compared in eight players from the second French League at the early follicular (EF), late follicular (LF) and mid-luteal (ML) phases of their menstrual cycle, determined by the calendar method. The movement patterns, expressed as meters per minute, were recorded during competitive matches using devices placed on the player’s ankle. Our results showed significantly lower distances covered at moderate and high velocity in the EF phase than in the LF and ML phases (Cohen’s d effect size = 1.03 and 0.79, respectively). The total distance covered during matches and the number of sprints also were reduced during EF compared with LF (d = 0.78 and 0.7, respectively). Overall, the total distance and distance covered at low velocity were significantly lower during the second half-time of the matches (d = 1.51), but no menstrual cycle phase × game period interaction was noted. In conclusion, our study suggests that EF may impact the movement pattern of sub-elite women soccer players during competitive matches, without any modulation of this effect by the playing time. Despite the low sample size, these results can be useful for coaches and support staff to modulate training loads and player rotation during soccer games.

Changes in adipose tissue microRNA expression across the menstrual cycle in regularly menstruating females: a pilot study.

Cyclical changes in hormone profiles across the menstrual cycle are associated with alterations in metabolic control. MicroRNAs (miRNAs) contribute to regulating metabolic control, including adipose tissue metabolism. How fluctuations in hormonal profiles across the menstrual cycle affect adipose tissue miRNA expression remains unknown. Eleven healthy, regularly menstruating females underwent four sampling visits across their menstrual cycle. Subcutaneous abdominal adipose tissue and venous blood samples were collected at each sampling visit. Luteinizing hormone (LH) tests, calendar counting, and serum hormone concentrations were used to determine menstrual cycle phases: early-follicular (EF), late-follicular (LF), postovulatory (PO), and midluteal (ML). Serum follicle-stimulating hormone, LH, estrogen, progesterone, and testosterone were determined using multiplex magnetic bead panels and enzyme-linked immunosorbent assays. Global adipose tissue miRNA expression levels were determined via microarray in a subset of participants (n = 8) and 17 candidate miRNAs were validated by RT-qPCR in the whole cohort (n = 11). Global analysis of adipose tissue miRNA expression identified 33 miRNAs significantly altered across the menstrual cycle; however, no significant differences remained after correcting for multiple testing (P > 0.05). RT-qPCR analysis of candidate miRNAs revealed miR-497-5p expression was significantly altered across the menstrual cycle ([Formula: see text] = 0.18, P = 0.03); however, post hoc tests did not reveal any significant differences between menstrual cycle phases (P > 0.05). miR-30c-5p was associated with testosterone concentration (R2 = 0.13, P = 0.033). These pilot data indicate differences in adipose tissue miRNAs in healthy women across the menstrual cycle and a weak association with ovarian hormones. Further research in larger sample sizes is required to confirm regulation of miRNA expression across the menstrual cycle.

Evidence of reduced peripheral microvascular function in young Black women across the menstrual cycle.

Black women (BLW) have a higher prevalence of cardiovascular disease (CVD) morbidity and mortality compared with White women (WHW). A racial disparity in CVD risk has been identified early in life as young adult BLW demonstrate attenuated vascular function compared with WHW. Previous studies comparing vascular function between premenopausal WHW and BLW have been limited to the early follicular (EF) phase of the menstrual cycle, which may not reflect their vascular function during other menstrual phases. Therefore, we evaluated peripheral microvascular function in premenopausal WHW and BLW using passive leg movement (PLM) during three menstrual phases: EF, ovulation (OV), and mid-luteal (ML). We hypothesized that microvascular function would be augmented during the OV and ML phases compared with the EF phase in both groups, but would be attenuated in BLW compared with WHW at all three phases. PLM was performed on 26 apparently healthy premenopausal women not using hormonal contraceptives: 15 WHW (23 ± 3 yr), 11 BLW (24 ± 5 yr). There was a main effect of race on the overall change in leg blood flow (ΔLBF) (P = 0.01) and leg blood flow area under the curve (LBF AUC) (P = 0.02), such that LBF was lower in BLW. However, there was no effect of phase on ΔLBF (P = 0.69) or LBF AUC (P = 0.65), nor an interaction between race and phase on ΔLBF (P = 0.37) or LBF AUC (P = 0.75). Despite peripheral microvascular function being unchanged across the menstrual cycle, a racial disparity was apparent as microvascular function was attenuated in BLW compared with WHW across the menstrual cycle.NEW & NOTEWORTHY This is the first study to compare peripheral microvascular function between young, otherwise healthy Black women and White women at multiple phases of the menstrual cycle. Our novel findings demonstrate a significant effect of race on peripheral microvascular function such that Black women exhibit significant attenuations in microvascular function across the menstrual cycle compared with White women.

Impact of Follicular Menstrual Phase on Body Composition Measures and Resting Metabolism.

This study aimed to identify the effects of early follicular (EF) and midfollicular (MF) menstrual phases on body composition, resting metabolic rate (RMR), and respiratory quotient (RQ) assessment accuracy to identify an optimal testing period. Body composition was obtained from a four-compartment (4C) criterion model (fat mass (FM), fat-free mass, body fat percent, and dual-energy x-ray absorptiometry (DXA; FM, lean mass (LM), trunk FM, and trunk LM) in 19 eumenorrheic females (mean ± SD: age, 21.3 ± 3.1 yr, body mass index, 23.6 ± 1.8 kg·m-2). RMR (kcal·d-1) and RQ (a.u.) were measured via indirect calorimetry for 25 min. Body composition, RMR, and RQ were measured during the EF and MF phases. Dependent-samples t-tests were used to compare outcomes between EF and MF. 4C outcomes were similar between phases (P > 0.05). During EF, the following 4C components were significantly greater (P < 0.05): body volume (mean difference (MD) ± SD, 0.70 ± 1.05 L), extracellular fluid (MD ± SD, 0.27 ± 0.51 L), and body mass (MD ± SD, 0.56 ± 0.80 kg). DXA-measured LM, body fat percent, trunk LM, and trunk FM were similar (P > 0.05); however, DXA FM was significantly greater during EF (MD ± SD, 0.29 ± 0.40 kg; P = 0.005), yet within measurement error of the device. Although RMR was not significantly different between phases (MD ± SD, 6.0 ± 190.93 kcal·d-1; P > 0.05), RQ was significantly higher during EF (mean ± SD, 0.03 ± 0.06 a.u.; P = 0.029) compared with MF. Body composition from 4C and DXA do not seem to be affected beyond measurement error as a result of compartmental changes from the menstrual cycle. During MF, women oxidized more fat as demonstrated by a lower RQ. Researchers should aim to be more inclusive and schedule testing for females within 11-12 d from the onset of menstruation.