Modulating effects of the menstrual cycle on cardiorespiratory responses to exercise under acute hypobaric hypoxia

The purpose of this study was to examine the hypothesis that the menstrual cycle-induced modulation of the cardiorespiratory response to exercise might be altered by acute exposure to altitude. During both the luteal and follicular phases, 9 moderately trained female subjects with normal menstrual cycles performed incremental exercise to maximal effort on a cycle ergometer at sea level (SL) and under hypobaric hypoxia (HH) at the equivalent of 3,000 m altitude. Both at rest and during exercise, minute ventilation (.VE) and oxygen uptake (.VO(2)) did not differ between the luteal and follicular phases (either at SL or HH). However, the ratio of .VE to .VO(2) (.VE /.VO(2)), both at rest and during peak exercise, was greater in the luteal phase than in the follicular phase under HH conditions. Furthermore, the partial pressure of end-tidal carbon dioxide (PETCO(2)) during exercise was lower in the luteal phase than in the follicular phase in HH. These results suggest that the menstrual cycle-induced modulation of the ventilatory response to exercise may be altered under acute hypobaric-hypoxic conditions.     

Influence of the menstrual cycle on proenkephalin peptide F responses to maximal cycle exercise

Proenkephalin peptide F [107–140] is an enkephalin-containing peptide found predominantly within the adrenal medulla and is co-packaged with epinephrine within adrenal medullary chromaffin granules. Peptide F has been shown to have the classic opioid analgesia effects along with immune cell interactions. This is only the second peptide F study in women, and in it we compare the responses of peptide F to a maximal cycle exercise test and recovery values over the follicular and luteal phases of the menstrual cycle. Eight untrained (directly documented in this study) women who were eumenorrheic performed a progressive maximal exercise test to volitional exhaustion on a cycle ergometer, once during the follicular phase, and once during the luteal phases of the menstrual cycle. Blood was obtained pre-exercise, immediately post-exercise and at 0, 15, and 30 min into recovery. Typical exercise changes in response to the cycle tests were observed with blood lactate increases that remained elevated 30 min into recovery. No significant exercise-induced elevations were observed for peptide F concentrations with exercise nor were any differences observed between the two menstrual phases. Thus, the effects of the menstrual cycle on peptide F concentrations appear to be minimal under the conditions of this investigation. With high concentrations of peptide F observed at rest (approx. 0.2–0.3 pmol ml⁻¹) pre-exercise arousal mechanisms may have obviated any exercise-induced response. In addition, inhibition via elevated epinephrine may have inhibited any post-exercise increases and finally adrenal medullary capacity for circulatory concentrations of peptide F may have been reached in such untrained women. Pre-exercise arousal mechanisms potentially related to analgesia may also be involved to prepare untrained women for the stress of maximal exercise.     

Do gender differences exist in the ventilatory response to progressive exercise in males and females of average fitness?

Gender differences in lung volumes and flow rates, and in respiratory control have been documented previously. How these gender differences affect exercise responses in normal subjects is less clear, particularly as many studies involved highly fit subjects. This study aimed to investigate potential gender differences occurring during progressive exercise in healthy males and females of average fitness. Fourteen males and ten females of mean (SD) age 23 (0.35) years completed a progressive exercise test to exhaustion on a cycle ergometer, with a ramp increase of 15 W min⁻¹ (female) or 20 W min⁻¹ (male). All females were studied during the follicular phase of their menstrual cycle. Cardiorespiratory variables were measured, breath by breath, and values were compared at rest, at 40 W, at physiologically equivalent workloads below, at and above the gas exchange threshold and at peak oxygen uptake (V̇O_2peak). Mean V̇O_2peak (SEM) was 32.4 (2.01) ml kg⁻¹ min⁻¹ for the females and 41.9 (1.80) ml kg⁻¹ min⁻¹ for the males. Females had a significantly lower end-tidal partial CO₂ pressure at rest and throughout exercise. Increases in exercise minute ventilation were achieved by a significantly greater tidal volume in males, whereas females adopted a significantly greater breathing frequency. Ratings of respiratory discomfort were significantly greater in the male group at physiologically equivalent workloads compared to the female group. This study shows gender differences exist in the ventilatory and sensory response to progressive exercise in untrained subjects. Further work is required to ascertain if these effects are altered during the luteal phase of the menstrual cycle.     

Induction of menstrual disorders by strenuous exercise in untrained women

We performed a prospective study of 28 initially untrained college women with documented ovulation and luteal adequacy to determine whether strenuous exercise spanning two menstrual cycles would induce menstrual disorders. To ascertain the influence, if any, that weight loss might exert, we randomly assigned the subjects to weight-loss and weight-maintenance groups. Subjects were expected to run 4 miles (6.4 km) per day, progressing to 10 miles (16.1 km) per day by the fifth week, and to engage daily in 31/2 hours of moderate-intensity sports. The normalcy of the menstrual cycles during the period of exercise was judged independently according to clinical and hormonal criteria, the latter comprising serial measurements of gonadotropin and sex-steroid excretion. A higher percentage of abnormalities proved to be detectable by hormonal means (P less than 0.02). Only four subjects (three in the weight-maintenance group) had a normal menstrual cycle during training. In the weight-loss group, the number of women who had luteal abnormalities as compared with those who lost the surge in luteinizing hormone altered significantly over time, the latter occurring more frequently (P less than 0.01) as training progressed. Within six months of termination of the study, all subjects were again experiencing normal menstrual cycles. We conclude that vigorous exercise, particularly if compounded by weight loss, can reversibly disturb reproductive function in women.     

The Effects of Menstrual Cycle Phase on Cardiovascular and Pulmonary Responses to Behavioral and Exercise Stress

The present study was designed to compare the differential cardiopulmonary and hemodynamic responses of Type A and B women to an exercise and a psychological stressor. In addition, the effects of menstrual cycle phase on the resting and response levels of a wide range of physiological variables were explored. Thirty-two women participated in a progressive exercise stress test and a threat of shock video game during both the luteal and follicular phases of the menstrual cycle. Half of these subjects expressed the coronary-prone behavior pattern referred to as Type A, as assessed by the Jenkins Activity Survey. The remaining women were relatively free of these behaviors (Type B). Heart rate, oxygen consumption, carbon dioxide production, minute ventilation, and end-tidal carbon dioxide were monitored and recorded on a breath-by-breath basis. Systolic and diastolic blood pressure measures were taken at 2-min intervals. Results indicated similar baseline, exercise, and behavioral stress responses among Type A and B women. The stress responses were also the same between the follicular and luteal phases for all measured physiological variables. However, resting levels of heart rate, metabolism, and ventilation were all elevated at rest during the luteal phase. A regression analysis based on the exercise heart rate and oxygen consumption data demonstrated that a majority of subjects exhibited heart rate responses in excess of that expected during the psychological stressor. These data are discussed with special reference to possible mechanisms of the pathophysiology of cardiovascular disease.     

The effects of exercise intensity on thermoregulatory responses to exercise in women

We investigated the influence of altering exercise intensity (150, 300, and 450 kpm/min) on the resetting of the core temperature threshold for the onset of the sweating rate (M(sw)) and the alteration of sweating sensitivity during the menstrual cycle in women. Five women underwent cycling exercise for 30 min in both the luteal and follicular phases under controlled neutral environmental conditions (T: 25 degrees C, RH: 55%). A significantly higher rectal temperature (T(re)) was seen in the luteal phase at all exercise intensities, and the same time course of the T(re) response with a constant difference of approximately 0.2 degrees C was shown between the follicular phase and the luteal phase. The T(re) threshold for M(sw) was also apparently shifted rightward a constant value of 0.2 degrees C from the follicular phase to the luteal phase, independent of the alteration of exercise intensity. The slope of the M(sw)-T(re) relationship in the follicular phase did not differ from that in the luteal phase. These results indicate that (1) a rightward shift in the T(re) threshold from the follicular phase to the luteal phase can be observed independent of any alteration of the exercise intensity; and (2) the sensitivity of M(sw) is also not physiologically influenced by exercise intensity. Thus, alterative thermoregulation during the menstrual cycle was fundamentally unaffected by the change of exercise intensity.     

Changes in peak expiratory flow and respiratory strength during the menstrual cycle

This study evaluated the spirometry and respiratory static pressures in 17 young women, twice a week for three successive ovulatory menstrual cycles to determine if such variables changed across the menstrual, follicular, periovulatory, early-to-mid luteal and late luteal phases. The factors phases of menstrual cycle and individual cycles had no significant effect on the spirometry variables except for peak expiratory flow (PEF) and respiratory static pressures. Significant weak positive correlations were found between the progesterone:estradiol ratio and PEF and between estrogen and tidal volume (r = 0.37), inspiratory time (r = 0.22), expiratory time (r = 0.19), maximal inspiratory pressure (r = 0.25) and maximal expiratory pressure (r = 0.20) and for progesterone and maximal inspiratory pressure (r = 0.32) during the early-to-mid luteal phase. Although most parameters of the spirometry results did not change during the menstrual cycle, the correlations observed between sexual hormones and respiratory control variables suggest a positive influence of sexual female hormones controlling the thoracic pump muscles in the luteal phase.     

Effects of menstrual phase and parental history of hypertension on cardiovascular response to cognitive challenge

The effects of parental history of hypertension and menstrual phase on systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) responses to two frustrating cognitive tasks were examined in 47 normotensive, young adult women. Subjects with and without a parental history of hypertension were scheduled to be tested during either the follicular (days 7-11 of a 28-day cycle) or luteal (days 17-22) phase of the menstrual cycle. During the laboratory session, HR, SBP, DBP, and self-report of affective states were measured while subjects performed two cognitive tasks (mental arithmetic and concept formation). Results indicated that the magnitude of SBP responses to the two tasks was significantly greater in subjects tested during the follicular phase than in subjects tested in the luteal phase of the menstrual cycle. No effect of parental hypertension was observed on cardiovascular response measures, though offspring of hypertensive parents reported experiencing significantly less anger during the tasks than subjects with normotensive parents.     

Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty‐seven women underwent a modified Trier Social Stress Test during the early follicular, late follicular, and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity, while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle‐related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se.     

Adipocyte insulin action during the normal menstrual cycle

The relationship between the menstrual cycle and insulin sensitivityis unclear. The aim of this study was to investigate insulinsensitivity during the normal menstrual cycle using the physiologicalinsulin target organ adipose tissue. A total of 23 normal healthyvolunteers were studied, nine of whom were in the follicularphase, and 14 of whom were age and body mass index-matched andin the luteal phase of the menstrual cycle. Adipocyte insulinreceptor binding was measured and adipocyte insulin action wasassessed by measuring initial rates of 3–0-methylglucoseuptake and by inhibition of lipolysis. The maximum specificinsulin receptor binding was significantly higher in subjectsstudied during the follicular phase of the menstrual cycle comparedto subjects studied during the luteal phase (1.81 ± 0.13versus 136 ± 0.15% per 10 cm2 cell surface, P < 0.05).Maximum rates of 3–0-methylglucose transport were 1.70± 0.22 versus 1.75 ± 0.22 pmol/10 cm2/5 s in thefollicular and luteal phase respectively and were not significantlydifferent between the two groups. The maximum percentage lipolysisinhibition observed was 42.5 ± 7.5% in the follicularphase and 39.9 ± 7.4% in the luteal phase (not significant).This study demonstrated that there is a reduction in insulinreceptor binding in the luteal phase of the normal ovulatorymenstrual cycle. The post-receptor action of insulin is notaffected between the two phases of the menstrual cycle.     

Sex steroid hormones and circulating IgE levels.

The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies.     

Gustatory changes associated with the menstrual cycle.

We studied changes in the palatability and gustatory functions as they correlate with the menstrual cycle in 30 healthy females with regular menstrual cycles. The gustatory function was investigated by conducting electrogustometry and by the filter-paper disk method with taste solutions in the follicular and luteal phases of the same subjects. The responses to a questionnaire revealed that appetite was enhanced prior to menstruation in 14 cases (46.7%). The results of electrogustometry showed that the threshold in the domain of the chorda tympani nerve was 0.3 +/- 3.4 dB in the follicular phase and -0.9 +/- 2.8 dB in the luteal phase. Although the threshold in the luteal phase indicated a statistically significant decrease (p < 0.05), the difference was so small that the change could not be subjectively discriminated. The threshold in the domain of the glossopharyngeal nerve was 2.6 +/- 4.0 dB in the follicular phase and 1.7 +/- 3.9 dB in the luteal phase, with no significant difference between the two values. Gustatory thresholds as obtained by the filter-paper disk testing were not significantly different between the follicular and luteal phases. Thus, although the taste function may change through the menstrual cycle, changes in gustatory thresholds are minimal and remain within the normal range.     

Effects of sex, phase of the menstrual cycle and gonadal hormones on pain in healthy humans

Sex differences in pain have been noted; women typically report more pain than men. Gonadal hormones may influence pain reports, and, moreover, such hormones may help to explain sex differences and menstrual cycle differences in pain. This study measured venipuncture and intravenous catherization pain during the follicular and luteal phases of the menstrual cycle in regularly menstruating women. Pain was also assessed in a group of men. Pain ratings were higher in women than men. In women, pain ratings did not differ between the follicular and luteal phases. Estradiol and progesterone increased from follicular to luteal phases. Within-phase analyses revealed that pain ratings were positively correlated with estradiol and progesterone during the luteal phase. Moreover, increases in estradiol and progesterone across the menstrual cycle were positively correlated with increases in pain. These findings suggest that variations in gonadal hormones during the menstrual cycle influence the experience of pain in healthy women.     

The relationship between exercise-induced oxidative stress and the menstrual cycle

The purpose of this study was to investigate the relationship between exercise-induced oxidative stress and the menstrual cycle in healthy sedentary woman. Eighteen women with regular menstrual cycles participated in this research. The subjects monitored their basal body temperature (BBT) and carried out a urinary ovulation test (twice) for 2 months prior to the study to determine their menstrual cycle. The subjects performed bicycle ergometer exercise (for 30 min at 60% O_2max) in each phase (menses, follicular and luteal phases) of the menstrual cycle. Serum estradiol and progesterone concentrations were determined from blood that was collected at rest. Serum thiobarbituric acid reactive substances (TBARS), total superoxide dismutase (T-SOD) and extracellular superoxide dismutase (EC-SOD) were determined as markers of oxidative stress in blood samples collected at rest and after exercise. TBARS was significantly lower after exercise [2.4 (0.5) nmol/ml] in the follicular phase, and T-SOD was significantly lower after exercise [3.2 (1.2) U/ml] in the luteal phase. EC-SOD did not show a significant change after exercise during each phase of the menstrual cycle. Furthermore, there was a negative correlation between estradiol and T-SOD (r=–0.46, P<0.05) and between estradiol and EC-SOD (r=–0.55, P<0.05) during the menses. All data are presented as the mean value and its standard deviation.The results of this study suggest that when the estradiol level is high in a menstrual cycle, free radicals produced as a consequence of exercise may be easily eliminated by sedentary women with normal menstrual cycles.     

Morphometric analysis of fibroblasts of the mammary lobular stroma during the follicular and luteal phases of the menstrual cycle

We determined the nuclear volume of fibroblasts of the normal mammary lobular stroma during the follicular and luteal phases of the menstrual cycle. Twenty patients aged 15 to 35 years and eumenorrheic for at least 6 months were randomly assigned to 2 groups, i.e., 10 women in the follicular phase and 10 in the luteal phase. The nuclear volume was 34.4 micron 3 and 98.8 micron 3 for the follicular and luteal phases, respectively, with the difference being statistically significant (p < 0.05). These data suggest a higher metabolic activity in the mammary intralobular stroma during the luteal phase of the menstrual cycle, probably due to a synergistic action of estradiol and progesterone.     

Changes of respiratory sinus arrhythmia during the menstrual cycle depend on average heart rate

To evaluate the complex time course of changes in respiratory sinus arrhythmia (RSA) during the menstrual cycle, daily beat-to-beat morning recordings of heart rate (HR) were carried out in 26 healthy female subjects (age 20–29 years) during two menstrual cycles. For determination of fast, vagally mediated variations of HR we used a robust time-domain measure of RSA (logRSA). We found pronounced changes in HR during the menstrual cycle with a minimum in the early follicular phase and a maximum in the late luteal phase. There were large differences between individuals in the fluctuations of logRSA during the menstrual cycle that were related to average HR: subjects with a low HR exhibited higher values of logRSA in the luteal compared to the follicular phase, whereas the trend was reversed in subjects with a high HR. The difference of extreme points of logRSA fluctuations (early follicular and mid luteal phase) was correlated to average HR (r=–0.64, P<0.001). We conclude that different patterns of RSA fluctuations occur depending on the level of average HR. Electronic Publication     

Cyclical variation of serum neutral endopeptidase lost in asthmatics: A pilot study.

Angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) are two metalloproteases, which have both been isolated from the airways. With the knowledge that young girls experience a worsening of asthma with fluctuations in oestrogen levels, we attempted to establish whether there is a change in ACE or NEP levels throughout the menstrual cycle, accounting for unhydrolysed inflammatory mediators in the airways. Asthmatics and normal controls (n=7) were studied through the follicular and luteal phases of the menstrual cycle. Peak flow rates and serum ACE levels showed no significant difference in either group. There was a four-fold increase in NEP levels in the follicular phase of normal women. Asthmatics had high levels of NEP throughout the cycle, in both the follicular and luteal phases. These results demonstrate an alteration of normal physiology in asthmatics, which might be a natural response to background inflammation.     

Changes in nociceptive flexion reflex threshold across the menstrual cycle in healthy women

OBJECTIVE: We assessed the influence of changes in steroid hormones across the menstrual cycle on the spinal nociceptive reflex. METHOD: We studied in 14 healthy women during the follicular and luteal phase the nociceptive flexion reflex (RIII reflex), an objective neurophysiological method that allows exploring possible abnormal functioning of the pain-control system. The basal body temperature (BBT) was used to evaluate the different phases of the ovarian cycle. The menstrual distress questionnaire (MDQ) was also applied for monitoring somatic and psychological symptoms during the cycle. RESULTS: During the luteal phase, the threshold of the RIII reflex (Tr) and the psychophysical threshold for pain (Tp) were both significantly reduced compared with the follicular phase. Moreover, the reflex threshold in the luteal phase was negatively correlated to the total MDQ score of the recording day. CONCLUSIONS: A higher sensitivity to pain stimuli was observed during the luteal phase of the menstrual cycle, which probably results from a reduction in the inhibitory descending control on spinal nociceptive flexion reflex. Complex neuromodulatory interactions of ovarian steroids with other systems of neurotransmission (especially serotonergic) may account for these observations.     

Vascular volume dynamics during ergometer exercise at different menstrual phases

Summary Five female Caucasians performed cycle ergometer exercise in a hot environment (32 C dry bulb, 30 C wet bulb) both early in the follicular phase and in the middle of the luteal phase of the menstrual cycle. During each menstrual phase, the exercise was performed once following hyper-hydration and once after 24-h fluid deprivation. More rapid increases in hemoglobin concentration and osmoconcentration, as well as decreases in plasma volume, were observed during exercise in the follicular phase, more notably following hypohydration. The data suggest that the phase of the menstrual cycle as well as the preexercise fluid status of the subject may be important determinants of vascular volume dynamics during exercise.Supported by National Institutes of Health Training Grant HL-07050     

Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome

BACKGROUND: We evaluated basal and dynamic hormonal markers [(FSH, inhibin B, estradiol and anti-Mullerian hormone (AMH)] during the follicular phase and luteal phase of the menstrual cycle and ultrasonic ovarian morphology as predictors of IVF outcome. METHODS: Fifty-six women, aged <38 years, with normal day 3 FSH levels were included prospectively. Serum estradiol, inhibin B and AMH were measured before and 24 h after administration of 300 IU of recombinant FSH on cycle day 3-4 and during the luteal phase. Ovarian volume and antral follicle count (AFC) were evaluated on cycle day 3-4. The predictive value of oocyte number and pregnancy were assessed using uni- and multivariate analysis. RESULTS:Poor responders (<6 oocytes) had significantly lower luteal AMH levels, while high responders (>20 oocytes) had significantly higher AFC, AMH and luteal stimulated inhibin B and estradiol than normal responders. Multivariate regression analyses showed that the best models for predicting oocyte number included AFC, follicular phase AMH and stimulated inhibin B. Only AMH showed a significant difference between pregnant and non-pregnant women at both cycle phases. CONCLUSIONS: In young women (<38 years), AFC or basal AMH and stimulated inhibin B predict ovarian response for IVF. The only predictor for pregnancy is follicular or luteal phase AMH.