Psychophysiological and neuroendocrine responses to laboratory stressors in women: Implications of menstrual cycle phase and stressor type

This study assessed stressor and menstrual phase effects on psychophysiological and neuroendocrine responses to laboratory stressors in freely cycling women (N = 78, ages 18-45). Participants performed counterbalanced stressors [Paced Auditory Serial Addition Test (PASAT) or cold pressor test (CP)] during their follicular and luteal menstrual cycle phases between 1:00 and 3:00 p.m. to control for cortisol rhythm. Participants rested 30-min, performed the stressor, and then recovered 30-min while electrocardiography continuously monitored heart rate (HR). Systolic (SBP) and diastolic blood pressure (DBP), salivary cortisol, and state anxiety were assessed at timed intervals. HR, SBP, and cortisol varied more over the course of luteal than follicular phase testing. A three-way interaction revealed state anxiety reactivity was greater with the PASAT during the follicular phase. DBP showed equal and persistent reactivity with both stressors during both cycle phases. Results extend the stressor-specific HPAA hypothesis and have important methodological implications for women's biopsychology research.     

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.     

Interactive effects of type A personality and psychological and physical stressors on human cardiovascular functions

The first part of this study examined the relationship(s) between Type A behavior scores and heart rate, blood pressure and impedance derived cardiovascular measures in response to discrete stressors during a standardized psychophysiological assessment. Expts. 2A and 2B considered cardiovascular responses to dynamic exercise stress alone and in combination with psychological and cold pressor tests. Gender and stroke volume changes during the psychological stress correlated 0.45 (P less than 0.02) with Type A score. Subscale scores of Job Involvement correlated 0.78 (P less than 0.02) with stroke volume, total systemic resistance and heart rate during the psychological stressor, and systolic blood pressure during the cold pressor task. The combined effects of psychological stress and dynamic exercise on systolic and diastolic blood pressure were significantly greater than the individual effects of these stressors. The use of impedance cardiography in measuring cardiovascular variables that correlate with Type A behavior, during psychophysiological assessments, may further elucidate our understanding of Type A behavior in addition to providing information about how stress interacts with aerobic exercise.     

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.     

女大学生月经周期应激敏感性的生理心理评估

目的:评估女大学生在月经周期不同阶段应激敏感性的变化。方法:在经前、经后和排卵期对29名月经周期规律的女大学生进行静息、心算任务的心理生理测试。结果:心率变化最显著,排卵期的心率显著大于经前和经后;在排卵期和经后心算心率显著大于静息心率,而在经前两者之间无显著差异;在心率变异性上,仅发现低频成分在静息状态显著大于心算状态;皮肤电反应在心算状态显著大于静息状态。结论:女大学生在经前应激敏感性最高。     

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.     

Psychoneuroendocrine stress responses and mood as related to the menstrual cycle

Psychoneuroendocrine stress responses were studied in normally ovulating women in the follicular, ovulatory, and luteal phases of two consecutive menstrual cycles. Psychologic stress was induced by having the subjects perform a battery of cognitive tasks under time pressure. Blood samples were drawn after each session for radioimmunoassay of 17 beta-estradiol, progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, prolactin, cortisol, and androstenedione. Urine samples were obtained for estimation of adrenaline, noradrenaline, and cortisol. The results showed that psychoneuroendocrine stress responses as estimated by urinary excretion of adrenaline and noradrenaline varied significantly across the menstrual cycle, the highest values being obtained in the luteal phase. Self-reported mood and somatic symptoms showed distinct phase-related changes, with more negative mood states predominating in the luteal and menstrual phases and increased positive mood states in the follicular and ovulatory phases.     

Influences of the Normal Menstrual Cycle on Physiologic Functioning During Behavioral Stress

The purpose of this study was to evaluate the influence of the normal menstrual cycle on lipoprotein, cardiovascular, and neuroendocrine stress responses. Fifteen normally-cycling, healthy women participated in a series of behavioral tasks during the menstrual, follicular, and luteal phases of their menstrual cycle. These women had established menstrual cycle regularity for the three months prior to enrollment in this study, were free from menstrual cycle disturbances, biochemically confirmed that they ovulated, and displayed appropriate patterns of reproductive hormone fluctuations during the study period. Heart rate, blood pressure, low density lipoprotein-cholesterol, and total cholesterol all demonstrated significant elevations from baseline levels during tasks. No differences in the magnitude of stress responses during the three menstrual cycle phases were noted for any physiological variable. We conclude that the hormonal fluctuations that occur in healthy, normally-cycling women during the menstrual cycle do not influence the stress responses that were investigated here. Significant influences of menstrual cycle phase previously reported in the literature, albeit not in a consistent direction, may have been due to the recruitment of women with menstrual cycle irregularities, and to the failure to adequately verify menstrual cycle phase.     

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.     

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.     

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.     

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.     

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)     

Cardiovascular responses to psychological and physiological stressors during the menstrual cycle

Psychological and physical stress reactivity was studied in 15 females in two phases of the menstrual cycle (cycle days 5-7 and 24-26) and in 15 males. Each female was matched for age and time between sessions with a male. There was a significant phase-related difference in cardiovascular reactivity among the females. Females in the luteal phase reacted significantly more to the cold pressor but not to the mental arithmetic test. There were significant sex differences in systolic blood pressure, the males displaying higher levels during provocation, as well as during control conditions. The females were more reactive in heart rate to the mental stressor when changes from control conditions to stress were calculated. When the data were analyzed separately for smokers and non-smokers, there was a significant interaction between menstrual cycle phase and smoking. In the luteal phase, the female smokers were more reactive in systolic blood pressure than the non-smokers. The male smokers were more reactive than the non-smokers in diastolic blood pressure response to mental arithmetic, but not to the cold pressor test. Significantly higher levels of cortisol and aldosterone were found in the luteal phase as compared with the follicular phase. The cortisol levels were higher in the males than in the females in the follicular phase, whereas the female aldosterone concentrations in the luteal phase were higher than those of the males.     

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.     

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.     

Cardiovascular Reactivity in Type A and B Males to Mental Arithmetic and Aerobic Exercise at an Equivalent Oxygen Uptake

Cardiovascular hyperreactivity (i.e., response in excess of metabolic requirements) to psychological stress has been implicated in the development of coronary heart disease. The purpose of this study was to evaluate cardiovascular hyperreactivity to psychological stress in Type A and B subjects. Fifteen Type A and 15 Type B young men performed mental arithmetic and cycle ergometry tasks. Linear regressions were calculated for each dependent variable during exercise with oxygen uptake serving as the independent variable. All cardiovascular variables were significantly correlated (p less than .0001) with oxygen uptake during exercise. The regression equations obtained during exercise were then used to predict the value of each cardiovascular variable at the oxygen uptake level obtained during mental arithmetic for each person. Repeated measures ANOVA compared responses observed during arithmetic with responses predicted from exercise at an equivalent oxygen uptake in Type A and B subjects. Heart rate, total peripheral resistance, and mean arterial pressure were significantly greater (p less than .0001) and stroke volume was significantly lower (p less than .0002) during arithmetic than during exercise, while Heather index, cardiac output, and arteriovenous oxygen difference did not differ significantly. No significant differences were found between Type A and B males. Results demonstrated that cardiovascular hyperreactivity was equally robust across Type A and B subjects.     

Responses to laboratory psychosocial stress in postpartum women

OBJECTIVE: Lactation has been associated with attenuated hormonal responses to exercise stress in humans. This study was designed to determine the effect of lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and anxiety responses to psychological stress. METHOD: The Trier Social Stress Test was administered to 24 lactating women, 13 postpartum nonlactating women, and 14 healthy control women in the early follicular phase of the menstrual cycle. Lactating women were stressed at least 40 minutes after last feeding their infant. RESULTS: ACTH, cortisol, heart rate, diastolic blood pressure, systolic blood pressure, and subjective anxiety ratings were all significantly increased in response to the psychological stress (all p <.0001). There were no differences among the three groups in any of these responses to the stress. However, postpartum nonlactating women did have a persistently higher systolic blood pressure and lower cardiac vagal tone than the lactating women and control subjects. In addition, the typical negative correlation between cardiac vagal tone and heart rate was consistently higher in lactating women than nonlactating postpartum women and controls, which suggests stronger vagal control of heart rate in lactating women. In addition, there was no change in oxytocin or allopregnanolone in response to the stress, and baseline oxytocin and allopregnanolone levels did not differ among the three groups. CONCLUSIONS: These results indicate that physiological and subjective responses to social stress are not attenuated in lactating women tested at least one hour after feeding their infant. However, enhanced vagal control of cardiac reactivity was observed in lactating women. In addition, postpartum women who did not lactate showed evidence of increased sympathetic and decreased parasympathetic nervous system tone.     

The impact of menstrual cycle phase on cardiac autonomic regulation

This study investigated menstrual cycle phase differences in heart rate (HR) and RR interval variability (RRV) in 49 healthy, premenopausal, eumenorrheic women (age 30.2±6.2 years). HR and RRV were computed from ambulatory 24-h electrocardiogram, collected for up to 6 days, with at least 1 day each during early to midfollicular and midluteal menstrual phases. Phase effects on HR and RRV were assessed using linear mixed effects models with a random intercept to account for the correlation of observations within each subject as well as intrasubject variation. During follicular phase monitoring, women had significantly lower average HR (−2.33 bpm), and higher standard deviation, the root mean squared successive difference, and high frequency (0.04–0.15 Hz) and low frequency (0.15–0.40 Hz) RRV than during the luteal phase. These results provide strong support for the influence of menstrual phase on cardiac autonomic regulation in premenopausal women.     

Cardiovascular Responses to the Combination of Caffeine and Mental Arithmetic, Cold Pressor, and Static Exercise Stressors

The present study examined cardiovascular responses to the combination of caffeine (250mg) and mental arithmetic, cold pressor, and static exercise stressors in 48 healthy males. Subjects were tested in a within-subject, placebo-controlled, double-blind design. Repeated measurements of heart rate, finger temperature, respiratory sinus arrhythmia, forearm blood flow, and blood pressure were obtained during a pre-drug resting baseline, a post-drug resting baseline, the three stressor tasks, and a recovery baseline. The primary analyses were 2(Drug) x 5(Period) x 6(Stress Order) MANCOVAs using pre-drug baseline values as covariates. Significant period main effects were observed for all measures. Significant drug main effects were observed for blood pressure, finger temperature, respiratory sinus arrhythmia, and forearm blood flow. The significant changes in blood pressure and finger temperature produced by caffeine combined in an additive fashion with the effects produced by the stressors. Significantly greater increases in forearm blood flow and heart rate during mental arithmetic on the caffeine day suggested a potentiation of sympathetic, beta-adrenergic activity. Questionnaires administered during baseline periods to assess psychological responses to stress and caffeine revealed a potentiation of anxiety and anger responses to stress on the caffeine day.