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.     

Fluctuations of serum bile acid concentrations during the menstrual cycle.

Fasting primary bile acid conjugates were measured in 44 women by radioimmunoassay methods. Bile acid values were significantly greater in the 21 women who were in the first half of the menstrual cycle than in the 23 women in whom blood was sampled during the second half of the cycle. Similar measurements were made at weekly intervals after menstruation in five subjects; increased values were observed in the first week. It is concluded that serum bile acid values fluctuate during the menstrual cycle.     

Serum leptin levels during the menstrual cycle of healthy fertile women.

Leptin is a protein, produced by adipose tissue, which has cytokine and hormonal properties. Serum leptin levels can be considered as a measure of body fat mass, and are involved in regulation of body weight. Previous studies suggest that leptin may have an additional role in reproduction, and there is also evidence for involvement in the hypothalamic-pituitary-gonadal axis. In this study, we investigate the possible changes in serum leptin concentration throughout the menstrual cycle. Samples were collected from apparently healthy, fertile women at different stages in their menstrual cycle, timed precisely according to the luteinising hormone (LH) surge. Mean serum leptin levels were significantly higher in the luteal phase (median 11.4 ng/mL) than in the follicular phase (median 10.0 ng/mL) (P < 0.001). In addition, mean serum leptin levels correlated with body mass index (r = 0.54, P < 0.05), but showed no correlation with luteal-phase progesterone levels. Results showed that levels of serum leptin vary during the menstrual cycle, and add to the mounting evidence that leptin has a role in reproduction. These fluctuations should be taken into account whenever studies are performed using female subjects.     

T-lymphocyte reactivity during the menstrual cycle in women

Reactivity of blood lymphocytes to nonspecific mitogenic stimulation with phytohemagglutinin (PHA) was measured in nine healthy, regularly cycling women at three phases of their menstrual cycles corresponding to peak levels of estradiol (midfollicular phase), peak levels of progesterone (midluteal phase), and the lowest levels of both hormones (menstrual phase). Sampling points were verified by radioimmunoassay of estrogen, progesterone, luteinizing hormone, and follicle-stimulating hormone. There were significant increases in reactivity associated with an increasing concentration of PHA and with autologous plasma vs AB plasma. However, no differences were found in reactivity to PHA over the three menstrual cycle phases and correlational analyses indicated no relationship between counts and any of the hormones measured.     

Visual perception in women during the menstrual cycle

Twelve females were tested at four times during the menstrual cycle with a visual detection task and a visual pattern discrimination task. Mood levels and confidence ratings were evaluated for each session. In addition to the behavioral testing, plasma samples were collected and radioimmunoassayed for estradiol, progesterone, luteinizing hormone, and follicle stimulating hormone levels. Visual detection fluctuated significantly during the menstrual cycle with impaired performance occurring at the premenstrual session. In contrast to previous reports, the impaired performance was not related to lowered confidence ratings or to mood levels.     

Diurnal sleep/wake-related immune functions during the menstrual cycle of healthy young women

SUMMARY  Animal and human studies have related the sleeping/waking brain to the immune system. Because women are more susceptible to certain immunological illnesses, and sex steroids regulate immune functions, it was investigated whether the diurnal sleep/wake pattern of aspects of cellular immune functions and interleukin-1 (IL-1) and IL-2-like activities differed during low and high progesterone phases of the menstrual cycle.
Eleven healthy women, mean age 24y, were assessed over 24h with serial venous blood samples. Peripheral blood monocytes were assayed for mitogen responses, i.e. phytohemagglutin (PHA) and pokeweed (PWM) and natural killer (NK) cell activities. Plasma was assayed for IL-1 and IL-2-like activities, cortisol and progesterone. Data were standardized by Z transformation and analysed by repeated-measures analysis of variance by comparing high ( N = 5) vs. low ( N = 6) progesterone phases.
During the high progesterone phase, delayed slow-wave sleep (SWS) onset time and reduced amount of SWS was accompanied by a delay in the decline of NK cell activity, but rise in PHA activity following sleep onset. With the low progesterone phase, the pattern was similar to men with an early sleep decline in NK cell and late sleep rise in PHA activities. PWM rose during the night and plasma IL-1-like activity peaked during midday and during nocturnal sleep irrespective of the amount of progesterone.
Slow-wave sleep and sleep-related NK cell and PHA activities differed over the menstrual cycle, but not PWM response. Increases in plasma IL-1 functions during midday and night are consistent with predisposition to sleepiness during these times.     

Phasic menstrual cycle effects on the control of breathing in healthy women

This study examined the effects of menstrual cycle phase on ventilatory control. Fourteen eumenorrheic women were studied in the early follicular (FP; 1-6 days) and mid-luteal (LP; 20-24 days) phase of the menstrual cycle. Blood for the determination of arterial PCO(2) (PaCO(2)) , plasma strong ion difference ([SID]), progesterone ([P(4)]), and 17beta-estradiol ([E(2)]) concentrations were obtained at rest. Subjects performed a CO(2) rebreathing procedure that included prior hyperventilation and maintenance of iso-oxia to evaluate central and peripheral chemoreflex, and nonchemoreflex drives to breathe. Resting PaCO(2) and [SID] were lower; minute ventilation (V (E)), [P(4)] and [E(2)] were higher in the LP versus FP. Within the LP, significant correlations were observed for PaCO(2) with [P(4)], [E(2)] and [SID]. Menstrual cycle phase had no effect on the threshold or sensitivity of the central and/or peripheral ventilatory chemoreflex response to CO(2). Both (V (E)) and the ventilatory response to hypocapnia (representing nonchemoreflex drives to breathe) were approximately 1L/min greater in the LP versus FP accounting for the reduction in PaCO(2) . These data support the hypothesis that phasic menstrual cycle changes in PaCO(2) may be due, at least in part, to the stimulatory effects of [P(4)], [E(2)] and [SID] on ventilatory drive.     

Changes in body weight and body composition during the menstrual cycle

Objectives

The general perception is that menstrual cycle is a factor related to body weight and body composition fluctuations in women. The lack of a standardized methodology of the so far conducted studies has led to controversial results. The aim of the current study is to identify if there are any changes in body weight and body composition during the menstrual cycle.

Methods

In the current study measurements of body weight, circumferences, skinfolds and body composition with bioelectrical impedance analysis were conducted twice per week in 42 women during their menstrual cycle.

Results

Body weight was found to be statistically significantly higher during menstruation compared to the first week of the menstrual cycle by 0.450 kg, which could be attributed to a statistically significant increase of 0.474 kg observed in extracellular water. No other statistically significant changes were observed regarding body composition.

Conclusions

An increase of approximately 0.5 kg was observed during women's menstrual cycle, mostly due to extracellular fluid retention at menstruation days. These findings could be taken into account to interpret body weight and composition periodic fluctuations in women of reproductive age.     

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.     

Changes in thrombin-stimulated platelet malondialdehyde production during the menstrual cycle.

Forty normal women had thrombin-stimulated platelet malondialdehyde (MDA) production measured during their menstrual cycle. Twenty women in this group were taking the combined oral contraceptive pill (OCP). Platelet MDA production was found to fall by 30% during normal menstruation and the week when the subjects were not taking a combined OCP, but it remained constant throughout the remainder of the cycle. No significant change in initial platelet aggregation response to stimulation by thrombin, change in plasma thrombin clotting time, plasma heparin neutralising activity (HNA), or plasma antithrombin III (AT-III) activity was seen when the platelet MDA production was reduced. The bleeding time results showed some variation throughout the menstrual cycle but these did not appear to be related to the variation in platelet MDA production.     

Serum concentrations of dimeric inhibins, activin A, gonadotrophins and ovarian steroids during the menstrual cycle in older women

The transition from regular ovarian cyclicity to menopause is associated with a rise in the circulating concentrations of follicle stimulating hormone (FSH), despite the maintenance of serum oestradiol concentrations during the perimenopause. The aim of this study was to compare the pattern of secretion of dimeric inhibins, activin A, gonadotrophins and steroids in regularly cycling women of 40-50 years with normal and raised early follicular phase serum FSH concentrations and young women (25-33 years) during the menstrual cycle. Blood samples were taken prospectively almost daily throughout the menstrual cycle. Women recruited were classified into three groups: (i) older women with normal FSH [(ON-FSH), day 3 FSH <8 mIU/ml, n = 10]; (ii) older women with raised FSH [(R-FSH), day 3 FSH >8 mIU/ml, n = 6] and (iii) young normal FSH (YN-FSH) women, age 25-32 years (n = 6). Cyclic patterns of serum inhibins and activin A were similar in the ON-FSH and YN-FSH groups. The R-FSH group had significantly lower concentrations of inhibin A prior to the luteinizing hormone (LH) surge and in the mid-luteal phase and lower concentrations of inhibin B in the early follicular phase compared with the ON-FSH group. Serum concentrations of activin A, progesterone and oestradiol were similar in all three groups. It is concluded from this study that the rise in early follicular phase serum FSH in older women is associated with a decrease in circulating concentrations of inhibin B in the early follicular phase. However, lower circulating concentrations of inhibin A in the luteal phase of the R-FSH group may also contribute to the rise in early follicular phase FSH concentrations during the menstrual cycle, although further studies with larger numbers are required to confirm this observation.     

Variations in carotid arterial compliance during the menstrual cycle in young women

The effect of menstrual cycle phase on arterial elasticity is controversial. In 10 healthy women (20.6+/-1.5 years old, mean+/-s.d.), we investigated the variations in central and peripheral arterial elasticity, blood pressure (carotid and brachial), carotid intima-media thickness (IMT), 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). Carotid arterial compliance (simultaneous ultrasound and applanation tonometry) varied cyclically, with significant increases from the values seen in M (0.164+/-0.036 mm2 mmHg-1) and F (0.171+/-0.029 mm2 mmHg-1) to that seen in the O phase (0.184+/-0.029 mm2 mmHg-1). Sharp declines were observed in the EL (0.150+/-0.033 mm2 mmHg-1) and LL phases (0.147+/-0.026 mm2 mmHg-1; F=8.51, P<0.05). Pulse wave velocity in the leg (i.e. peripheral arterial stiffness) did not exhibit any significant changes. Fluctuations in carotid arterial elasticity correlated with the balance between oestradiol and progesterone concentrations. No significant changes were found in carotid and brachial blood pressures, carotid artery lumen diameter, or IMT throughout the menstrual cycle. These data provide evidence that the elastic properties of central, but not peripheral, arteries fluctuate significantly with the phases of the menstrual cycle.     

Changes of ventilation and ventilatory response to hypoxia during the menstrual cycle

The relationship between change in hypoxic sensitivity in respiration, defined as increment in ventilation per drop of arterial O₂ saturation , with the phase change from follicular to luteal and those in resting pulmonary ventilation , mean inspiratory flow (V _T/T _I), alveolar partial pressures of CO₂ and O₂ ( and , respectively) and body temperature was studied in 10 women. There was a significant relationship between % increase in hypoxic sensitivity and decrement of resting that occurred in the luteal phase. However, no significant relationships were observed between change in hypoxic sensitivity and those in the remaining parameters studied. The intersubject variation in % increase in resting during the luteal phase was not associated with that in % increase in hypoxic sensitivity. The results indicate that the contribution of increased hypoxic sensitivity to increasing during the luteal phase is variable among subjects. Reasons for the increase in hypoxic sensitivity with hypocapnia are discussed.     

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.     

重组FS-288表达及ELISA法检测正常女性月经周期血中FS水平变化

目的：表达重组FS-288，制备抗FS抗体，建立特异性的FS双抗体夹心ELISA检测系统。方法：采用表达质粒构建及诱导表达方法制备重组FS-288，杂交瘤技术制备抗FS单抗，酶联免疫方法测定血中FS水平。结果：以抗FS多克隆抗体和单克隆抗体建立了 FS双抗体夹心ELISA法，其敏感度为25 pg/well，正常女性血中 FS水平随月经周期呈周期性变化，在排卵前2 d达峰值，而 acivin A无明显的周期性变化。结论：FS水平随月经周期改变，提示FS可能与性腺轴的内分泌调控有关。     

Heart rate variability and endogenous sex hormones during the menstrual cycle in young women

To our knowledge, the relationship between all four endogenous female sex hormones and resting cardiac autonomic function has not been studied. The aim of the current study was to examine the association between the normal endogenous levels of oestrogen (17beta-oestradiol), progesterone, luteinising hormone and follicle-stimulating hormone and heart rate variability (HRV) during the menstrual cycle in young eumenorrheic women. Ten healthy, young, female subjects volunteered for this study. HRV and endogenous hormone levels were recorded at three phases of the menstrual cycle: menses (day 3.8 +/- 0.5), ovulation (day 15.8 +/- 0.7) and luteal (day 22.1 +/- 0.4) to ensure HRV recordings at times of low (menses) and high (ovulation and luteal) hormonal influence. Heart rate recordings were obtained from supine resting subjects and analysed on a Holter analysis system. Total power (TP, 0-1.0 Hz), low frequency (LF, 0.041-0.15 Hz), high frequency (HF, 0.15-0.80 Hz) and LF/HF components of HRV were examined. Despite a significantly greater HR at ovulation and normal cyclic variations in all endogenous sex hormone levels, no measure of HRV was significantly different between menstrual cycle phases. Significant correlations between oestrogen levels and absolute measures of HRV at ovulation were identified. The results of the current study demonstrated that the normal cyclic variations in endogenous sex hormone levels during the menstrual cycle were not significantly associated with changes in cardiac autonomic control as measured by HRV. Significant correlation between peak oestrogen levels and HRV measures at ovulation provided further support for the reported cardioprotective effects of oestrogen in healthy females.     

Changes in serum cytokine concentrations during the menopausal transition

OBJECTIVE: The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. METHODS: Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. RESULTS: Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. CONCLUSION: We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.     

Alterations in the insulin-like growth factor system during the menstrual cycle in normal women

Objectives: To evaluate the effects of endogenous estrogens and progestins on the IGF-system during the normal menstrual cycle in healthy premenopausal women not using contraceptive drugs. Methods: Nine women had fasting blood samples obtained at 2–3 days intervals during a 5 week study period. Plasma levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3, estradiol and progesterone were measured by radioimmunoassay (RIA) in each sample. IGFBP-3 was also evaluated by Western ligand blot (WLB) and immunoblot. Any differences between the menstrual phase (defined as day 1–5), follicular and luteal phases (separation based on plasma estradiol and progesterone values) were evaluated by the Friedman test. Results: A small but significant difference in plasma levels of IGF-I (P<0.01) and IGFBP-3 (P<0.05) measured by RIA between the three phases were seen with the highest levels found during the follicular phase. No change in plasma levels of IGFBP-1 and IGF-II was found and immunoblots did not reveal any alteration in the ratio of fragmented to intact IGFBP-3 during the menstrual cycle. A positive correlation between plasma levels of IGF-I and estradiol was seen in 8 out of 9 patients (P=0.012). Conclusions: The finding of a slight but significant higher level of plasma IGF-I in the follicular and luteal phases compared with the menstrual phase suggests plasma estradiol may influence the level of this growth factor. This hypothesis is further supported by the finding of a correlation between plasma levels of IGF-I and estradiol but not progesterone in individual patients at different times during the menstrual cycle.