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.     

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.     

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.     

Does corpus luteum locally affect follicular growth negatively?

In this study bilateral ovarian follicular growth during the luteal phase was investigated in relation to the ovary where ovulation occurred. The diameter of the largest follicle in the contralateral ovary without corpus luteum and in the ipsilateral ovary with corpus luteum was measured using vaginosonography in a total of 66 natural cycles of 27 normally cycling women undergoing treatment with intrauterine insemination (IUI). None of the women received ovarian stimulation or luteal support. Follicles from 2 to 11 mm in diameter were measured in early luteal phase (day +1 to +4), mid-luteal phase (day +5 to +9) and late luteal phase (day +10 onwards). The mean diameters of the largest follicle in the contralateral ovary without corpus luteum during the early, mid- and late luteal phases were 6.81 +/- 1.33 (mean +/- SD), 6.14 +/- 1.29 and 5.71 +/- 1.17 mm respectively, while those of the ipsilateral ovary with corpus luteum were 6.48 +/- 1.40, 5.65 +/- 1.47 and 4.98 +/- 1.19 mm respectively. While there was no significant difference during the early luteal phase, the mean diameter of the largest follicle in the ipsilateral ovary with corpus luteum was significantly smaller than that of the contralateral ovary without corpus luteum during the mid-luteal phase (P < 0.004) and the late luteal phase (P < 0.0005). These results indicate that the corpus luteum locally affects neighbouring follicular growth negatively during the luteal phase of the menstrual cycle, with the most pronounced effect expressed in the mid- and late luteal phases.      

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.     

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.     

Tobacco withdrawal in women and menstrual cycle phase

Because negative mood is a characteristic of both tobacco withdrawal and menstrual discomfort, withdrawal may vary by menstrual cycle phase. Tobacco withdrawal, mood, and menstrual discomfort were assessed in premenopausal women who quit smoking during either the follicular (Days 1-14 postmenstrual onset; n = 41) or luteal (Day 15 or longer postmenstrual onset; n = 37) phase of the menstrual cycle and maintained biochemically verified smoking abstinence during the postquit week. Women quitting during the luteal phase reported significantly greater increases in tobacco withdrawal and self-reported depressive symptoms than women quitting during the follicular phase. These results indicate that selecting a quit-smoking day early in the follicular phase may attenuate withdrawal and negative affect in premenopausal female smokers.     

Perceived poor sleep quality in the absence of polysomnographic sleep disturbance in women with severe premenstrual syndrome

Women with severe premenstrual syndrome report sleep‐related complaints in the late‐luteal phase, but few studies have characterized sleep disturbances prospectively. This study evaluated sleep quality subjectively and objectively using polysomnographic and quantitative electroencephalographic measures in women with severe premenstrual syndrome. Eighteen women with severe premenstrual syndrome (30.5 ± 7.6 years) and 18 women with minimal symptoms (controls, 29.2 ± 7.3 years) had polysomnographic recordings on one night in each of the follicular and late‐luteal phases of the menstrual cycle. Women with premenstrual syndrome reported poorer subjective sleep quality when symptomatic in the late‐luteal phase compared with the follicular phase (P < 0.05). However, there were no corresponding changes in objective sleep quality. Women with premenstrual syndrome had more slow‐wave sleep and slow‐wave activity than controls at both menstrual phases (P < 0.05). They also had higher trait‐anxiety, depression, fatigue and perceived stress levels than controls at both phases (P < 0.05) and mood worsened in the late‐luteal phase. Both groups showed similar menstrual‐phase effects on sleep, with increased spindle frequency activity and shorter rapid eye movement sleep episodes in the late‐luteal phase. In women with premenstrual syndrome, a poorer subjective sleep quality correlated with higher anxiety (r = ?0.64, P = 0.005) and more perceived nighttime awakenings (r = ?0.50, P = 0.03). Our findings show that women with premenstrual syndrome perceive their sleep quality to be poorer in the absence of polysomnographically defined poor sleep. Anxiety has a strong impact on sleep quality ratings, suggesting that better control of mood symptoms in women with severe premenstrual syndrome may lead to better subjective sleep quality.     

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.     

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.     

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.     

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.     

Denial is associated with higher ambulatory blood pressure across the menstrual cycle

Background: Studies show that stress perception is associated with increased daily ambulatory blood pressure (BP) and that denying the negative effects of stress increases BP as well. Whether these effects persist over the menstrual cycle is unknown.

Aim: To examine the effects of measures of stress and stress denial on ambulatory work and home BP during the follicular and luteal phases of the menstrual cycle.

Subjects and methods: Seventy-one women (age?=?34.9?±?7.7 years) employed as secretaries or technicians wore an ambulatory BP monitor during the follicular (between day 7–10; Mean?=?8?±?2) and luteal (between day 19–25; Mean?=?22?±?2) phases of their cycle. During each phase, relationships between BPs averaged at work and home and various stress measures and demographic and anthropometric variables were examined using stepwise regression.

Results: Ambulatory BPs did not change from the follicular to luteal phase. Stress denial was generally associated with higher ambulatory BP (p?Conclusion: Stress denial has a persistent effect on BP, regardless of menstrual phase; however, shifts in the hormonal environment throughout the menstrual cycle may mediate other somatic and behavioural associations with BP.     

Changes of PSA concentrations in serum and saliva of healthy women during the menstrual cycle

This study investigated the changes of prostate specific antigen (PSA) concentrations in serum and saliva of women during the menstrual cycle. Thirty healthy volunteers (age 23-35 yr) were enrolled in the study. During the menstrual cycle, serum and saliva PSA concentrations on days 9 (follicular phase) and 14 (mid-cycle) were significantly higher than on days 4 (early follicular phase) and 21 (luteal phase). The expected changes in gonadal hormones were seen, as evidenced by significantly higher serum estradiol and progesterone concentrations during the midcycle and luteal phase, compared to the other phases of the cycle. Serum PSA concentrations were positively correlated with salivary PSA concentrations at all 4 times (days 4, 9, 14, and 21) of the menstrual cycle, but not with the serum progesterone or estrogen concentrations. This study suggests that salivary PSA, rather than being produced in the salivary gland, may reflect the serum PSA during the normal menstrual cycle.     

Plasma leptin concentrations are increased in women with premenstrual syndrome

Leptin is a metabolic regulator of the hypothalamic- pituitary-gonadal axis, and plays an important role in human reproduction. Its neuro-endocrine effects are mediated by interactions with receptors in the hypothalamus, where emotional drive is also controlled. We postulated that circulating leptin concentrations are increased in premenstrual syndrome (PMS), and that this may be associated with the psychological symptoms of the disease. We obtained fasting venous samples from 32 women with PMS and 28 women with asymptomatic menstrual cycles, matched for age, body mass index and menstrual cycle length. Leptin concentrations were measured by radioimmunoassay. Leptin concentrations increased significantly during the luteal phases of the menstrual cycles of the control and PMS groups as compared with the follicular phase, having excluded the 11 women with PMS and six controls found to be anovulatory on the basis of mid-luteal plasma progesterone concentrations from the analysis. A greater increase was observed in women with PMS than the controls (P: = 0.00006 and 0.003 respectively). Although leptin concentrations in the follicular and luteal phases were higher in PMS than the controls, the difference was only statistically significant between the follicular phases (P: = 0.001). There was no clear relationship between leptin and oestradiol or progesterone in this study. These findings suggest that leptin may play a role in the pathophysiology of the disease, and requires further evaluation.     

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     

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.     

Variations in resting frontal alpha asymmetry between high‐ and low‐neuroticism females across the menstrual cycle

Resting frontal alpha asymmetry measures the relative activation intensity across the left and right frontal regions that represent emotional experience. Here, the focus is on levels of alpha asymmetry between high‐ and low‐neuroticism females across the menstrual cycle. Resting alpha asymmetry in healthy females who scored high or low on neuroticism was assessed during the menstrual phase, the late follicular phase, and the midlate luteal phase. High‐neuroticism females exhibited lower relative left prefrontal activity than did low‐neuroticism females during the midlate luteal phase, as indexed by alpha₁ and alpha_Total asymmetry scores at the prefrontal electrode positions (FP_1/2). EEG results demonstrate that the resting frontal alpha asymmetry of high‐ and low‐neuroticism females was moderated by the menstrual cycle, and high‐neuroticism females should pay particular attention to their emotional experience during the midlate luteal phase.     

Food intake and the menstrual cycle in rhesus monkeys

Fourteen adult female rhesus monkeys were observed for 1 complete menstrual cycle, five of them for 2 cycles. Changes in LH, FSH, estrogens and progesterone were monitored daily. Mean hormonal concentrations followed patterns previously demonstrated in primates, with a typical late follicular phase estrogen peak preceeding the ovulatory LH and FSH surges. Maximal sexual skin color intensity paralleled the midcycle increase in estrogens. The results indicate that food intake fluctuated with changes in hormonal secretion. A significant decrease in the amount of food consumed correlated well with the midcycle estrogen and gonadotropin surges. The amount of food consumed during the luteal phase was greater than that of the early follicular phase.     

Fluctuations in carotid arterial distensibility during the menstrual cycle do not influence cardiovagal baroreflex sensitivity

Aim: Fluctuations in autonomic nervous functions throughout the menstrual cycle and the underlying mechanism concerning them are not well known. This study was designed to test the hypothesis that fluctuations in cardiovagal baroreflex sensitivity (BRS) throughout the menstrual cycles of young women are due to fluctuations in carotid arterial distensibility. Methods: In eight eumenorrhoeic healthy young women (18–24 years), we determined the variations in the carotid arterial distensibility coefficient (DC; via simultaneous ultrasonography and applanation tonometry), cardiovagal BRS (phase IV of the Valsalva manoeuvre and the sequence method; up‐ or down‐sequence spontaneous BRS), and serum oestradiol and progesterone concentrations at five points in the menstrual cycle (menstrual = M, follicular = F, ovulatory = O, early luteal = EL, and late luteal = LL). Results: Serum oestradiol and progesterone levels were consistent with the predicted cycle phases. Carotid arterial DC fluctuated cyclically, increasing significantly from the M (52.4 ± 4.9 × 10^?3 kPa^?1, mean ± SE) and F (52.7 ± 4.4) phases to the O (57.6 ± 4.4) phase and declining sharply in the EL (46.0 ± 4.0) and LL (45.1 ± 3.0) phases (F = 6.37, P < 0.05). Contrary to our prediction, however, cardiovagal BRS by the Valsalva manoeuvre (P = 0.73) or sequence method (up‐sequence spontaneous BRS; P = 0.84: down‐sequence spontaneous BRS; P = 0.67) did not change significantly during the menstrual cycle. Conclusion: The results suggest that, although carotid arterial distensibility fluctuates with the changes in ovarian hormone levels that occur during the menstrual cycle, the fluctuations in carotid arterial distensibility do not influence cardiovagal BRS.