The effect of dietary restriction and menstrual cycle on excess post-exercise oxygen consumption (EPOC) in young women.

The purpose of this study was to evaluate the effect of acute dietary restriction on excess post-exercise oxygen consumption (EPOC) in young women at two different phases of the menstrual cycle. Five young sedentary women (age 21-22 years) participated in this study. Each subject visited the laboratory eight times for measurement of EPOC. They performed cycle ergometer exercise for 60 min at a work rate corresponding to approximately 70% of VO2max under each four different conditions (i.e. standard diet/follicular phase (SF), standard diet/luteal phase (SL), restricted diet/follicular phase (RF) and restricted diet/luteal phase (RL)). The exercise was performed in the morning and VO2 was measured for the last 15 min of each hour for 7 h after the exercise. As a control, VO2 was also measured with an identical time schedule under the same four conditions but without exercise. EPOC was calculated as the difference of the VO2-time integral for 7 h between the exercise and control trial days in each of the four conditions (i.e. SL, SF, RL and RF). The diet was precisely controlled during 2 days (i.e. the test day and the day preceding it). The standard diet was 1600 kcal day-1 and the restricted diet was half of the standard diet. A two-way (dietary and menstrual cycle factors) ANOVA indicated that EPOC was significantly affected only by the dietary factor. The dietary restriction decreased EPOC compared to the standard dietary condition (SF 8.6 +/- 2.1, RF 5.3 +/- 1.6, SL 8.9 +/- 4.8, RL 4.0 +/- 1.2 l). These data indicate that for young sedentary women, EPOC is significantly lowered by prior acute dietary restriction but is not influenced by different phases of the menstrual cycle.     

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.     

Cardiovascular functioning during the menstrual cycle.

Variations in cardiovascular functioning during the 'normal' menstrual cycle have been little researched. Resting-blood pressures, resting-heart rate, rate-pressure product (RPP) and a derived index of fitness (Schneider Index) were monitored throughout natural, hormonally defined menstrual cycles. Volunteers were 26 women (20-48 years) who had regular (25-35 days) cycles. Their blood pressures and heart rate (at rest and according to Schneider's protocol) were measured at the same time daily (Monday-Friday) for 5 weeks. Daily, early morning-urine samples were assayed for sex hormones enabling accurate definition of cycle phase for each woman. Resting systolic-blood pressure was significantly higher in the ovulatory phase (P < 0.05) than in the follicular or luteal phases, but resting-diastolic pressures did not differ significantly between phases. Resting-heart rate was significantly higher in both ovulatory (P < 0.01) and luteal (P < 0.01) phases than in the menstrual and follicular phases. The Schneider Index was higher during the follicular phase than during the ovulatory (P < 0.005) or luteal (P < 0.01) phases, the RPP was higher during the ovulatory phase than during the bleeding (P < 0.05) and follicular (P < 0.005) phases. These findings provide a pattern of menstrual cycle-related variation in cardiovascular functioning that can be related to established actions of the ovarian steroids.     

Plasma volume during heat stress and exercise in women

Summary Five women were studied during exercise and passive heating to determine whether PV dynamics were affected by the menstrual cycle. The exercise bout (80% peak) on a modified cycle ergometer and the passive heat stress were done in a hot environment (T_a=50°C, P_w=1.61kPa) during the follicular and luteal phase. Esophageal temperature (T_es) was measured continuously. Blood samples were drawn after each 0.2° C increase in T_es and was measured at that time. Initial PV was estimated at rest during the follicular phase. PV changes from rest were calculated at each T_es from Hb and Hct. During passive heating, PV decreased by a mean volume of 156 (±80) ml to 2.83 (±0.09)l in the follicular phase. During the luteal phase, there was a larger volume reduction (300±100 ml) during passive heating, and the final PV was lower than in the follicular phase and averaged 2.47±0.181. During exercise, PV decreased 463 (±90) ml to 2.50 (±0.11) l in the follicular and 381 (±70) ml to 2.50 (±0.23) l in the luteal phase. These data indicate that there is a menstrual cycle effect on PV dynamics during passive heating such that more fluid is shifted out of the vasculature during the luteal phase. During severe exercise there is a greater fluid loss during the follicular phase, yet the final PV is not different between phases.     

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.     

Menstrual Cycle Phase is a Potential Confound in Psychophysiology Research

Effects of menstrual cycle phase on physiological levels and reactivity were studied in a withinsubject design with 20 women aged 18–30 years. Basal body temperature was monitored daily; follicular and luteal recording sessions occurred before and after the ovulatory temperature rise, respectively. The design consisted of task and rest periods, presented in counterbalanced order across phases. Half the subjects began during their follicular phase and half began during their luteal phase. Follicular and luteal phases were compared for differences between baseline resting levels, as well as for reactivity. The results showed menstrual phase differences in heart rate, pulse transit time, and EEG alpha, particularly during tasks, but no difference in reactivity. Habituation effects in the group that began during the follicular phase often masked luteal activation. In spite of the fact that not all statistical results achieved significance, the consistency of most trends supports the conclusion that physiological recording sessions with women might best be restricted to the follicular phase.     

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.     

Augmentation of exercise ventilation by medroxyprogesterone acetate

The influence of medroxyprogesterone acetate (MPA) on exercise performance was studied in a double-blind cross-over trial using six normal males to compare the exercise performance changes to those observed in a previous study of exercise responses of female subjects during the follicular and luteal phase of the menstrual cycle. A maximal progressive work exercise test on a cycle ergometer was performed after 2 weeks of placebo or MPA administration. Although five of six subjects spontaneously complained of increased exertional dyspnoea on MPA, no significant decreases were documented in maximal exercise time or in maximal oxygen consumption. A mean increase in exercise ventilation of 19% at low levels of exertion and 26% at high levels of exertion was documented, but no subject demonstrated evidence of ventilatory limitation. The increases in exercise ventilation observed in these male subjects after MPA administration were larger than those observed in the previous study comparing exercise ventilatory responses during follicular and luteal phases of the menstrual cycle. It seems possible that some other exercise-related modulator of the ventilatory response to exercise under the influence of progesterone is present in either male subjects receiving MPA or women with normal hormonal 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.     

No effect of menstrual cycle phase on fuel oxidation during exercise in rowers

The aim of this investigation was to examine the effects of menstrual cycle phase on substrate oxidation and lactate concentration during exercise. Eleven eumenorrheic female rowers (18.4 ± 1.9 years; 172.0 ± 4.0 cm; 67.2 ± 8.4 kg; 27.7 ± 4.8% body fat) completed 1 h rowing ergometer exercise at 70% of maximal oxygen consumption (VO_2max) during two different phases of the menstrual cycle: the follicular phase (FP) and the luteal phase (LP). Resting and exercise measurements of the whole body energy expenditure, oxygen consumption (VO₂), respiratory exchange ratio (RER), substrate oxidation and lactate blood levels were made. Energy expenditure, VO₂ and heart rate during the 1-h exercise were not significantly different (P > 0.05) among menstrual cycle phases. Resting RER and RER during the entire 1 h exercise period were not significantly different among menstrual cycle phases. There was an increase (P < 0.05) in RER in the transition between rest and exercise and a further increase in RER occurred after the first 30 min of exercise at both menstrual cycle phases. Blood lactate concentrations significantly increased in the transition between rest and exercise and remained relatively constant during the whole 1 h of exercise in both menstrual cycle phases. No menstrual cycle phase effect (P > 0.05) was observed for blood lactate concentrations. In conclusion, our results demonstrated no effect of menstrual cycle phase on substrate oxidation and blood lactate concentration during rowing exercise at 70% of VO_2max in athletes. Normally menstruating female rowers should not be concerned about their menstrual cycle phase with regard to substrate oxidation in everyday training.     

A prospective study evidencing rhinomanometric and olfactometric outcomes in women taking oral contraceptives.

BACKGROUND: The aim of this prospective study was to evaluate the changes in olfactory sensitivity of oral contraceptive (pill) users. METHODS: Sixty women underwent rhinomanometric and olfactometric determinations during the follicular, periovular and luteal phases of the menstrual cycle, and at day 7, 14 and 21 of contraceptive intake. Thirty-one women used 30 microg ethinyl oestradiol plus 75 microg gestodene and 29 women used 20 microg ethinyl oestradiol plus 150 microg desogestrel. RESULTS: Rhinomanometry showed higher but not statistically significant values during the periovular phase than in the follicular and luteal phases. Olfactometry showed a higher sensitivity during the follicular and periovular phases than during the luteal phase of the menstrual cycle. The rhinomanometric surveys in pill users were statistically different from those of the luteal phase (P < 0.02) and the follicular and periovular phases (P < 0.001). The olfactometric thresholds during the period of contraceptive use were statistically different from those of the follicular phase for a few odorous substances, and from those of the periovular phase for each odorous substance, but similar to those of the luteal phase (P = NS). CONCLUSIONS: Unlike the rhinomanometric airflow and trans-nasal pressure, the olfactory threshold to odours seems to depend on the variations of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives.     

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.     

Effects of human menstrual cycle on thermoregulatory vasodilation during exercise

Summary To investigate the effects of the menstrual cycle and of exercise intensity on the relationship between finger blood flow (FBF) and esophageal temperature (T_es), we studied four women, aged 20–32 years. Subjects exercised at 40% and 70% in the semi-supine posture at an ambient temperature of 20 C. Resting T_es was higher during the luteal phase than the follicular phase (P<0.01). There were no significant differences between the two phases in FBF, oxygen consumption, carbon dioxide production, heart rate or minute ventilation at rest and during exercise, respectively. Each regression line of the FBF-T_es relationship consists of two distinct segments of FBF change to T_es (slope 1 and 2). FBF increased at a threshold T_es for vasodilation ([T_{es 0}]) and the rate of FBF rise became greater at another T_es above this threshold ([T_{es 0}']). For both levels of exercise, [T_{es 0}] and [T_{es 0}'] were shifted upward during the luteal phase, but the slopes of the FBF-T_es relationship were almost the same in the two phases of the menstrual cycle. Increasing exercise intensity induced a significant decrease in slope 1 of the FBF-T_es relationship during the follicular (P<0.01) and the luteal phases (P<0.02), respectively. These results show that the set-point temperature may be shifted towards a higher level during the luteal phase of the menstrual cycle during exercise and that, as in males, the thermoregulatory vasodilator response is attenuated by increasing exercise-induced vasoconstrictor tone in proportion to exercise intensity during both phases of the menstrual cycle when heat storage is insufficient in women.Supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (grant no. 57770137)     

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.     

Effects of the menstrual cycle phase on the blood lactate responses to exercise

The effects of menstrual cycle phase on the blood lactate response to exercise were examined in eumenorrheic women (n=9). Exercise tests were performed at the mid-follicular and mid-luteal points in the menstrual cycle (confirmed by basal body temperature records and hormone levels). Blood lactates were measured at rest and during the recovery from exercise. Resting lactates were not different between the exercise tests; however, recovery lactates were significantly (p < 0.05) lower in the luteal compared to the follicular phase. The mechanism for these differences is unclear, but may be related to an estrogen mediated increased lipid metabolism inducing a concurrent reduction in carbohydrate metabolism. The present findings question the use of blood lactate monitoring as a suitable technique to measure exercise intensity in eumenorrheic women.     

Fluctuation of HER2 Expression in Breast Carcinomas during the Menstrual Cycle

The hormonal milieu at time of tumor surgery seems to have a significant impact on survival in premenopausal breast cancer patients. Indeed, surgery performed during the follicular phase of the menstrual cycle was suggested to correlate with a poor prognosis. To investigate the relationship between prognosis and menstrual cycle at time of surgery, we analyzed the expression of some markers associated with tumor aggressiveness, such as the hormone receptors, HER2, p53, Bcl2, and cathepsin D in breast carcinomas obtained from 198 premenopausal women who underwent surgery during different phases of the menstrual cycle. HER2 overexpression was found to fluctuate in hormone receptor-positive tumors. In actual fact, 20% of the tumors removed during the follicular phase scored HER2-positive, versus 8% of those removed during the luteal phase. Similarly, a number of hormone receptor-positive tumor specimens, obtained from the same patients during follicular and luteal phases, were scored HER2-positive when the sample was removed during the follicular phase and HER2-negative when removed in the luteal phase. Southern blot analysis of the HER2 gene indicated that, in hormone receptor-positive cases, the overexpression of HER2 is often not associated with gene amplification. The finding that overexpression of the HER2 gene, associated with tumor aggressiveness, can fluctuate according to the hormonal milieu may explain the increased survival of patients operated during the luteal phase. It is also relevant to the selection and treatment of patients most likely to benefit from anti-HER2 antibody therapy.     

Effect of menstrual phase on the acetate correction factor used in metabolic tracer studies.

The acetate correction factor is used to account for retention of carbon label in exchange reactions of the tricarboxylic acid cycle in studies estimating free fatty acid oxidation with carbon-labeled tracers. Previous evidence indicates that substrate utilisation and metabolic rate vary across the menstrual cycle, which may alter the correction factor. We therefore derived the acetate correction factor for each of three menstrual phases (early follicular [EF], late follicular [LF], and midluteal [ML] phase) from the fractional recovery of 13CO2 from a constant infusion of sodium-[1-13C] acetate during 90 min of submaximal exercise (60% VO2-max) in sedentary eumenorrhoeic women. There was no difference in the correction factor between the EF and LF or the LF and ML phases, but the correction factor derived in the ML phase was significantly lower than in the EF phase (p < 0.05). Neither energy expenditure nor whole body substrate utilisation during exercise varied significantly between menstrual phases and therefore cannot explain the observed difference in the correction factor. The lower correction factor in the ML phase, compared to the EF phase, would result in only a small increase of -6% in the calculated plasma free fatty acid oxidation rate.     

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.     

Food intake,body weight,and sweetness preferences over the menstrual cycle in humans

The body weight and reported food intake of 34 women were measured at the midpoint of the follicular and luteal phases of the menstrual cycle. Both body weight and reported food intake were significantly higher during the luteal phase than during the follicular phase. In addition, sweetness (sucrose) preferences were measured on both occasions before and after a glucose load. Examination of the pre- to post-load changes revealed a significant decline during the luteal phase and the absence of such a decline in the follicular phase. The results were discussed in terms of the influence of ovarian hormones on food regulation and carohydrate metabolism.     

Mental stress‐induced haemoconcentration in women: Effects of menstrual cycle phase

Objectives In women, variation in the incidence of myocardial infarction (MI) has been reported with phase of the menstrual cycle. Mental stress‐induced rheological and haemodynamic perturbations have been implicated in the triggering of MI. This study examined cardiovascular reactions to mental stress across the menstrual cycle, as a factor contributing to the known variation between the menstrual cycle phases in MI incidence. Methods Rheological and haemodynamic activity during rest and a prolonged mental stress task were assessed in 12 women during the follicular and luteal phases of the menstrual cycle. Results The stress task increased haematocrit, colloid osmotic pressure, blood pressure and heart rate, and decreased heart rate variability and R‐wave to pulse interval. However, there were no effects of menstrual phase on rheological or haemodynamic function at rest or in response to mental stress. There were also no moderating menstrual cycle effects for the rheological or haemodynamic reactions over time to this prolonged stress task. Conclusions Our findings do not support the hypothesis that variations in reactions to mental stress can explain the reported variations in risk for MI across the menstrual cycle.