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 menstrual cycle and neuroticism on females' emotion regulation

Fifteen highly neurotic women and 21 women who were low in neuroticism participated in this study. The women were surveyed three times over a single menstrual cycle during the mid-late luteal, menstrual, and late follicular phases. Each time, the participants were asked to use reappraisal to regulate their emotions, which were evoked by a sad film clip, and their subjective emotional experiences and physiological responses were recorded. The results showed that neuroticism had no impact on emotion regulation, and the females experienced fluctuations in their emotion regulation success over their menstrual cycle. During the menstrual phase, women reported significantly higher levels of reappraisal, but subjective sadness did not differ throughout the three phases. Additionally, the regulation effects on galvanic skin response (GSR) were smaller during the menstrual phase than in the mid-late luteal phase. These results suggested that women in the menstrual phase expended more effort but gained less success at regulating their emotions.     

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.     

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.     

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 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.     

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.     

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.     

Electrodermal activity in menstrual cycle phases: a comparison of within- and between-subjects designs

Electrodermal activity (EDA) changes in menstrual cycle were studied in two experiments. In both experiments subjects were presented with 16 80-dB tones; 15 tones were 4 s, 1000 Hz, and the last one - change trial - was a 6-s, 3000-Hz tone. In Expt. 1, a within-subjects design was employed, and 15 women were studied throughout a complete menstrual cycle. No significant changes in EDA associated with menstrual cycle phases were found, but significant decreases in electrodermal responsiveness during experimental sessions in EDA parameters were observed. In Expt. 2, with a between-subjects design, 56 women were divided in menstrual (n = 10), follicular (n = 12), ovulatory (n = 14), luteal (n = 13) and premenstrual (n = 7) groups, according to the cycle phase in which the subject was at the time of recording. At the ovulatory phase there were significant increases in skin conductance response (SCR) magnitude, skin conductance level, SCR habituation rate, and SCR amplitude to stimulus change, in relation to menstrual, luteal, and premenstrual phases. The discrepancies in the EDA data coming from the two experiments may be explained by practice effects appearing in Expt. 1.     

Auditory brainstem response in premenopausal women taking oral contraceptives

BACKGROUND: The aim of this prospective study was to evaluate the effects of the new monophasic oral contraceptives on the audiological system in premenopausal women. METHODS: The auditory brainstem response (ABR) was measured in 94 women during the follicular, periovular and luteal phases of one menstrual cycle in which ovulation was confirmed using sonography and serum progesterone concentration. The latencies for waves I, III and V were determined, and the inter-peak intervals were calculated for waves I-III, I-V and III-V. All 94 women began taking oral contraceptives: 23 women used 20 microg ethinyl estradiol (EE) plus 150 microg desogestrel, 24 women used 30 microg EE plus 75 microg gestodene, and 47 women used 15 microg EE plus 60 microg gestodene. During the third month of contraceptive intake, each subject was again tested for ABR, as above. RESULTS: The wave latencies and inter-peak intervals showed shorter values during the periovular phase with respect to the luteal phase (P < 0.05), the follicular phase for wave I and for inter-peak interval I-V (P < 0.05) of the menstrual cycle. All of the ABR results in pill users were statistically different from those of the periovular phase (P < 0.05), though similar to those of both the luteal and follicular phases (P = NS). CONCLUSIONS: ABR seems to depend on the variations of ovarian steroids during the menstrual cycle and during oral contraceptive intake.     

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.     

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.     

Menstrual cycle phase effects on prepulse inhibition of acoustic startle

Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating.     

Sleep patterns related to menstrual cycle phase and premenstrual affective symptoms

An ovulatory menstrual cycle is characterized by fluctuating levels of progesterone. Progesterone, a gonadal hormone known for its soporific and thermogenic effects, is present in negligible levels prior to ovulation and in high levels after ovulation. To describe and compare sleep patterns in relation to ovulatory cycles and premenstrual mood state, sleep was monitored in healthy women at two phases of the menstrual cycle. Results indicated that rapid-eye-movement (REM) latency was significantly shorter during the postovulatory (luteal) phase compared to the preovulatory (follicular) phase, but there was no significant difference in latency to sleep onset or the percentage of REM sleep. While there were no menstrual cycle phase differences in the percentages of various sleep stages, the women with negative affect symptoms during the premenstruum demonstrated significantly less delta sleep during both menstrual cycle phases in comparison with the asymptomatic subjects.     

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.     

Strength training effects on urinary steroid profile across the menstrual cycle in healthy women

Some studies suggest that performing strength training may cause alterations on the hypothalamic pituitary axis, resulting in steroid hormone variations. Intense training has been associated to slow the concentrations of estrogens and progesterone in women. The main purpose of this study was to evaluate the effects of strength training on the urinary steroid concentrations across the menstrual cycle phases. Twenty healthy women, regularly menstruating and not using pharmacologic contraceptives, performed a strength training during 8 weeks. Participants worked out 3 sets × 10 repetitions, with 2 min recovery time between sets, at 70–75 % of one maximum strength repetition. Urine samples were taken in three different phases of the menstrual cycle (menstrual, follicular and luteal) and they were collected both before and after training. Testosterone, DHEA, cortisol, cortisone, estradiol and progesterone concentrations were determined by gas chromatography-mass spectrometry. The results showed a significant decline after training in the urinary excretion of estradiol, during the menstrual and follicular phase, and progesterone, during the menstrual and luteal phase. No significant difference was observed for other steroid hormones. These data demonstrated that strength training can play an important role in the estrogen and progesterone metabolism in women, decreasing their levels across the menstrual cycle.     

Effects of the menstrual cycle on mood, neurocognitive and neuroendocrine function in healthy premenopausal women

BACKGROUND: Neurocognitive functioning may be impaired in the luteal phase of the menstrual cycle due to associated changes in hypothalamic-pituitary adrenal (HPA) axis function. This study examines the relationship between changes in neurocognition and HPA axis function in different phases of the menstrual cycle. METHOD: Fifteen female volunteers, free from psychiatric history and hormonal medication were tested twice, during mid-follicular and late-luteal phases in a randomized, crossover design. Mood, neurocognitive function, and basal cortisol and dehydroepiandrosterone (DHEA) were profiled. RESULTS: Relative to the follicular phase, verbal fluency was impaired in the luteal phase and reaction times speeded on a continuous performance task, without affecting overall accuracy. 'Hedonic' scores on the UWIST-MACL scale were decreased in the luteal phase. There was also evidence of changes in the function of the HPA axis, with 24 h urinary cortisol concentrations and salivary DHEA levels being significantly lower during the luteal phase. CONCLUSIONS: These data suggest that luteal phase HPA axis function is lower than in the follicular phase in premenopausal healthy women. This putative biological difference may be important for our understanding of the aetiopathogenesis of menstrually related mood change and neurocognitive disturbance.     

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.     

Endogenous overnight creatinine clearance, serum beta 2-microglobulin and serum water during the menstrual cycle

Endogenous overnight (22.00-08.00 hours) creatinine clearance and serum concentrations of beta 2-microglobulin and water were measured three times a week during 11 ovulatory menstrual cycles. In some of the women creatinine clearance changed more than 100% within a week from values below reference range to high normal levels. In all the women the creatinine clearance was higher during the luteal than during the follicular phase and correlated with the production of ovarian hormones. The urinary excretion rate of creatinine was highest during the luteal phase. Urinary volume, serum creatinine and serum water were not significantly influenced by the menstrual phases. An unexplained finding was a parallel change in the individual creatinine clearance and serum beta 2-microglobulin during the luteal, but not during the follicular phase. Our results suggest that ovarian hormones influence creatinine clearance during the menstrual cycle. One must therefore accept even considerable short-time variations in creatinine clearance in fertile women. It remains to be settled if these changes reflect true alterations in glomerular filtration rate or mainly changes in the urinary (tubular) excretion rate of creatinine.     

Estrogen modulates inhibitory control in healthy human females: evidence from the stop-signal paradigm

Animal studies point to a role of estrogen in explaining gender differences in striatal dopaminergic functioning, but evidence from human studies is still lacking. Given that dopamine is crucial for controlling and organizing goal-directed behavior, estrogen may have a specific impact on cognitive control functions, such as the inhibition of prepotent responses. We compared the efficiency of inhibitory control (as measured by the stop-signal task) in young women across the three phases of their menstrual cycle (salivary estradiol and progesterone concentrations were assessed) and in young men. Women were less efficient in inhibiting prepotent responses in their follicular phase, which is associated with higher estradiol levels and with higher dopamine turnover rates, than in their luteal or menstruation phase. Likewise, women showed less efficient inhibitory control than men in their follicular phase but not in their luteal or menstruation phase. Our results are consistent with models assuming that the over-supply of striatal dopamine in the follicular phase weakens inhibitory pathways, thus leading to enhanced competition between responses. We conclude that gender differences in response inhibition are variable and state dependent but not structural.