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.     

Hypothalamic-pituitary-ovarian dysfunction after prepubertal chemotherapy and cranial irradiation for acute leukaemia

BACKGROUND: We assessed adult hypothalamic-pituitary-ovarian function following treatment with chemotherapy and cranial irradiation for childhood acute lymphoblastic leukaemia. METHODS: The patients (n = 12) had median age at diagnosis of 4.7 years, and at assessment of 20.8 years. They collected a daily urine sample over two to five consecutive menstrual cycles (total of 41 cycles) for analysis of LH and steroid excretion. Blood sampling and ovarian ultrasound examination was performed in the early follicular phase. Sixteen healthy women with regular menstrual cycles were recruited as controls. RESULTS: Urinary LH excretion was significantly lower in patients throughout the cycle, particularly during the LH surge (P < 0.0001). The length of the luteal phase was significantly shorter in patients than in normal controls (12.2 +/- 0.3 versus 13.6 +/- 0.4 days, P = 0.01) with a high prevalence of short (< or =11 days) luteal phases (15/39 cycles). Luteal phase pregnanediol excretion was slightly but not significantly lower. Follicular and luteal phase excretion of oestrone was lower in patients than in controls (P = 0.01). Early follicular phase plasma oestradiol was also lower in the patient group (P = 0.032) although LH, FSH, inhibin A and B concentrations were similar. CONCLUSIONS: These data indicate that treatment for childhood leukaemia results in subtle ovulatory disorder in some patients, probably related to cranial irradiation. Follow-up of these women is required to detect any effect on reproductive potential.     

Sleep quality and the sleep electroencephalogram in women with severe premenstrual syndrome

STUDY OBJECTIVES: Women with severe premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) commonly report sleep disturbances, but the few studies using conventional polysomnographic measures have produced conflicting results. We investigated sleep quality and sleep composition using conventional and quantitative electroencephalographic analyses in women with severe PMS, as compared with that of controls. DESIGN AND PARTICIPANTS: Women (aged 18-40 years) were screened to ensure that their PMS symptoms were severe and that they had ovulatory menstrual cycles. Nine women with PMS or PMDD and 12 asymptomatic control subjects then had laboratory-based polysomnographic recordings at 2 phases of the menstrual cycle: follicular phase and late luteal (premenstrual) phase. RESULTS: Women with severe PMS reported a significantly poorer subjective sleep quality during the late luteal phase (P = 0.02), but there was no evidence of disturbed sleep based on the polysomnogram specific to premenstrual symptom expression: both groups of women had increased wakefulness after sleep onset (P = 0.02) and increased sigma power (P < 0.01), especially in the 14-to 15-Hz band during non-rapid eye movement sleep, in the late luteal phase compared with the follicular phase. There were, however, some group differences in electroencephalographic measures regardless of menstrual phase, including decreased delta incidence (P = 0.02) and increased theta incidence and amplitude (P < 0.05) in women with PMS, suggesting the possibility of sleep electroencephalogram trait markers in women with PMS. CONCLUSION: Perceived poor quality sleep is a characteristic of severe PMS, but sleep composition based on polysomnographic measures and quantitative electroencephalographic analysis does not differ in association with premenstrual symptom expression in the late luteal phase.     

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.     

Placental protein 14 in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium in the rhesus monkey

Placental protein 14 (PP14) is a glycoprotein which is secreted by secretory phase endometrium and decidua in women. Despite the suggestion that PP14 is involved in the process of endometrial maturation for blastocyst implantation, our understanding in this regard is poor. In the present study, the concentrations and distribution patterns of immunodetectable PP14 in the endometrium during proliferative and secretory phases of normal ovulatory menstrual cycles, as well as in implantation stage endometrium in naturally mated ovulatory cycles with or without early luteal phase mifepristone treatment, were investigated using the rhesus monkey as a primate model. Immunopositive PP14 was observed mainly in epithelial cells of glands and it was detected in one major immunopositive band at Mr 28 kDa in tissue homogenate and spent medium. The area of immunopositive precipitation of PP14 in glands was minimal in follicular phase endometrium, and was higher (P < 0.01) in early, mid- and late luteal phase endometrium compared with that in pre- and periovulatory phases of the cycle, but there was no change in its area profile in the glandular compartment throughout the luteal phase. Immunopositivity for PP14 in luminal contents of gland displayed an increasing profile from early to late secretory phases. Thus, the concentrations and the distribution of immunodetectable PP14 in luteal phase endometrium of the rhesus monkey showed marked similarity with those of human endometrium during the natural menstrual cycle. Although there was no marked change in the band characterstics for the protein in implantation stage endometrium following early luteal phase mifepristone treatment, it was markedly decreased (P < 0.01) in tissue homogenate and in vitro spent medium along with a lesser (P < 0.02) degree of immunoprecipitation in the glands in implantation stage samples of mifepristone treatment group compared with that in control group samples. Thus, the contragestional effect of early luteal phase mifepristone treatment appears to be associated with a decrease in the concentration of immunodetectable PP14 in implantation stage endometrial glands and its secretion in the rhesus monkey. It remains to be seen whether this decline is caused from direct antiprogesterone action on endometrial glands during progesterone dominance, or secondarily from associated retarded development of endometrium.      

The aetiology of galactorrhoea in women with regular menstruation and normal prolactin levels.

Fourteen primary infertile women with expressible galactorrhoea associated with regular ovulatory cycles and normal basal prolactin levels (group A) were matched for age and weight with 14 infertile women with regular menstruation but no galactorrhoea (group B). Both groups showed equivalent increases in prolactin levels after stimulation with 200 micrograms thyrotrophin-releasing hormone (TRH) during the follicular and luteal phases of the menstrual cycle. Patients in group A had a greater increase in luteinizing hormone levels after 100 micrograms i.v. injection of a luteinizing hormone-releasing hormone during the follicular phase (P less than 0.05). Following a 60 mg oral dose of buspirone hydrochloride on day 22 of the menstrual cycle, patients in group A had a greater increase in prolactin levels than patients in group B (P less than 0.01). This reflects hyper-responsive 5-hydroxytryptamine type 1A (5HT1A) receptors in group A patients and may explain the presence of galactorrhoea in these patients despite normal basal and post-TRH prolactin levels.     

The impact of the ovulatory cycle on cytokine production: evaluation of systemic, cervicovaginal, and salivary compartments.

To understand the impact of the menstrual cycle on immunologic parameters, we measured the level of cytokines and chemokines from plasma, cervicovaginal lavage (CVL), and saliva samples of 6 premenopausal women during the follicular and luteal phases of the ovulatory cycle. We demonstrate that the level of plasma interleukin-8 (IL-8) was 4-fold higher during the follicular phase than the luteal phase (p = 0.004), whereas plasma IL-1beta, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and TNF receptor II (TNFR II) were not altered during the ovulatory cycle. In the vaginal compartment, as measured from CVL samples, the levels of IL-6 and IL-1beta were both 5-fold higher in the follicular than the luteal phase (p = 0.0002 and 0.03, respectively). Salivary cytokine and chemokine samples were similar when measured during the luteal and the follicular phases. Additional analysis of lymphocyte subsets for phenotypic and functional markers indicated that they were not influenced by the ovulatory cycle. Collectively, these data suggest that IL-6, IL-8, and IL-1beta are differentially regulated during the ovulatory cycle.     

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.     

The influence of the menstrual cycle on upper airway resistance and breathing during sleep

STUDY OBJECTIVE: Female hormones, specifically progesterone, that peak in the luteal phase may play a significant role in protecting premenopausal women from sleep-disordered breathing. The influence of female hormones on upper airway resistance during sleep was investigated during the follicular and luteal phases of normal menstrual cycles. SETTING: Hospital-based sleep laboratory. DESIGN AND PARTICIPANTS: Healthy women with verified ovulatory cycles and without sleep complaints were recruited into the study. Sleep and upper airway resistance data (mean +/- SD) were collected on 2 nights from 11 women (21-49 years of age [28 +/- 9 years], body mass index of 22.8 +/- 3.6 kg/m2), once during the follicular phase (day 6-11) and once in the luteal phase (day 19-23) in random order. MEASUREMENTS AND RESULTS: Nasal resistance, standardized to a flow rate of 0.3 L/second, measured using posterior active rhinomanometry immediately prior to the sleep study, did not differ between the 2 phases. The respiratory disturbance index tended to be higher in the follicular phase than in the luteal phase and was above 5 per hour for 3 women in the follicular phase. Upper airway resistance, controlled for flow rate and body position, was calculated for 50 random breaths during wakefulness, stage 1, stage 2, slow-wave, and rapid eye movement sleep. During wake and stage 2 sleep, upper airway resistance was significantly higher in the follicular phase than in the luteal phase, as was the overall upper airway resistance combined for wake and across all sleep stages. Combining data from the 2 nights, compared to wake, upper airway resistance increased in stage 2, slow-wave, and rapid eye movement sleep. CONCLUSIONS: Within the menstrual cycle, upper airway resistance is lower in the luteal compared with the follicular phase.     

No cyclicity in serum vascular endothelial growth factor during normal menstrual cycle but significant luteal phase elevation during an in vitro fertilization program

PROBLEM: To compare changes in serum vascular endothelial growth factor (VEGF) levels during normal and in vitro fertilization (IVF) cycles. METHOD OF STUDY: Ten healthy women with ovulatory cycles and 37 infertile women participating in an IVF program were followed by frequent serum samples and with VEGF measurements throughout their cycles. RESULTS: Serum VEGF remained unchanged during the normal menstrual cycle, whereas the IVF program participants showed elevations in serum VEGF in the luteal phase of the cycle. When data from controls and patients were pooled, redundant midluteal VEGF level correlated with progesterone and with peak follicular phase estrogen level. The midluteal VEGF level in the IVF cycles was associated with body mass index (P < 0.01) and progesterone level (P < 0.05) by multiple regression. The 14 women conceiving tended to have higher VEGF levels than those failing to become pregnant. CONCLUSIONS: The IVF program was associated with increased synthesis of VEGF either in the ovaries, endometrium, or at other sites and this may be of significance for the outcome of IVF.     

A biochemical test for the direct assessment of endometrial function: measurement of the major secretory endometrial protein PP14 in serum during menstruation in relation to ovulation and luteal function

Circulating PP14 was measured by radioimmunoassay in ovulating (n = 12) and anovulatory (n = 3) women throughout the menstrual cycle, the highest levels of serum PP14 being seen during menstruation and in the late luteal phase in ovulating women. Mean serum PP14 levels on days 1-7 and 24-28 of the menstrual cycle were significantly higher than those observed from days 8 to 23 (P less than 0.0005 and P = 0.005 respectively). There was no difference in mean PP14 levels observed in the menstrual and luteal phase. By contrast, serum PP14 was rarely detected in anovulatory cycles. During the luteal phase, mean serum PP14 levels were apparently not related to serum progesterone levels. However, mean PP14 levels during the menstrual phase were significantly higher in the group of women with the highest progesterone production (Pmax greater than 39 nmol/l) (P less than 0.002) in comparison with levels seen in ovulating women with lower progesterone production (Pmax less than 32 nmol/l). These findings suggest that the synthesis and secretion of PP14 is influenced by ovulation and luteal function. Serum PP14 measurements may provide useful information about the endometrium in relation to fertility, and that these measurements during the menstrual cycle may distinguish between ovulatory and anovulatory cycles.     

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.     

Endometrial cathepsin D immunostaining throughout ovulatory and anovulatory menstrual cycles

The results of histological examination of the endometrium arenormal in most patients with unexplained sterility. CathepsinD is a ubiquitous lysosomal protease regulated by progesteronein the endometrium. Assays of concentrations of cathepsin Dmight be useful in determining the functional responses of theendometrium to progesterone. To examine this possibility, wequantified immunostaining of endometrial cathepsin D using animage analysis system in women with regular menstrual cycles.An endometrial sample was obtained during the proliferativeand luteal phases from 17 women with ovulatory menstrual cyclesand at the beginning and during the last 14 days of a cyclefrom 15 women having anovulatory menstrual cycles. In endometrialglands of ovulatory women, cathepsin D protein immunostainingincreased during the cycle and was significantly higher duringthe luteal than during the proliferative phase [51 ±38.1arbitrary units (AU) versus 118.2 ± 58.9 AU; P < 0.01].This increase was also observed in stromal cells, although toa lesser extent (28.6 ± 26.9 versus 41.5 ± 43.1AU; P = NS). In the endometrium of women with anovulatory menstrualcycles, cathepsin D staining was high both for the proliferativeand the luteal biopsies in glands (respectively 95 ±43 and 104 ± 51.3 AU) and stromal cells (respectively61.8 ± 33.8 and 75 ± 32.6 AU). In women with ovulatorycycles, cathepsin D staining was localized in the apical partof glandular cells during the proliferative phase and diffusedthroughout the cytoplasm during the luteal phase. In contrast,in women with anovulatory cycles, cellular localization of cathepsinD remained apical in glands, regardless of the day of biopsy.In conclusion, this study shows that the cytoplasmic localizationof cathepsin D might be a qualitative biological indicator ofendometrial gland responses to progesterone. This could be auseful tool for evaluating cell function, which is poorly testedby histology alone.     

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.     

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.     

Plasma beta-endorphin, pain thresholds and anxiety levels across the human menstrual cycle

Nine normally cycling women and seven other women employing oral contraception were tested during five phases (menstrual, follicular, ovulatory, luteal and premenstrual) of their menstrual cycle. The procedure consisted of administration of an anxiety inventory and determination of pain detection and pain thresholds in response to electric shock and the cold pressor task. Venipunctures were also performed and the plasma of normally menstruating women later assayed for beta-endorphin. Analyses revealed that the variance but not the mean levels in peripheral beta-endorphin levels significantly differed (p less than 0.01) across the menstrual cycle with the greatest amount of variance found during the ovulatory phase and the least during the luteal phase. The high variance during the period around ovulation was due to several subjects having extremely elevated beta-endorphin levels which possibly may have resulted from the occurrence of ovulation. Furthermore, a significant positive correlation between anxiety levels and beta-endorphin levels was found only during the menstrual phase. The absence of findings concerning cyclic variation in pain thresholds is contrary to earlier reports and indicates that such a phenomenon may be dependent upon the paradigm employed.     

Lower olfactory threshold during the ovulatory phase of the menstrual cycle

We investigated whether olfactory detection threshold is correlated with phase of the menstrual cycle. Three hundred and thirty-two women 13-49 years old were tested once during either the follicular, ovulatory, luteal or menstrual phase, and 15 women 20-43 years old were tested at each of these phases across one complete cycle. In three non-cycling control groups subjects were each tested once; 83 post-menopausal women 47-86 years old, 60 pre-pubertal girls 5-12 years old, and 183 men 17-30 years old. Odor detection thresholds were determined using sniff bottles containing -log9.5 to -log6.0 concentrations of amyl acetate presented in ascending order. Thresholds differed significantly across the cycle and were lowest during the ovulatory and highest during the menstrual phase. Thresholds for all control groups were higher than for the cycling women during the ovulatory phase. The results confirm that olfactory threshold is related to phase of the menstrual cycle and thus possibly to hormonal state.     

Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein

BACKGROUND: Ovulation has several similarities with inflammation and is closely connected to the activity of leukocytes and inflammatory cytokines. Since granulocytes are one of the major leukocytes, we focused our attention on the presence and local production of granulocyte colony-stimulating factor (G-CSF) in the human ovary. METHODS: The presence of G-CSF protein in the follicular fluid and perifollicular tissues was examined by Western blot analysis (n = 5) and immunohistochemical staining (n = 10). The relative expression levels of G-CSF mRNA in relation to GAPDH in granulosa, theca and luteal cells during the menstrual cycle were measured by quantitative RT-PCR using TaqMan technology (n = 15). RESULTS: G-CSF protein was detected in all follicular fluid and located mainly in granulosa cells of the follicle and luteal cells. The expression level of G-CSF mRNA in the late follicular phase was 137.6 +/- 18.5, which was approximately 10-fold greater than other phases during the menstrual cycle (P < 0.05). CONCLUSIONS: These results demonstrate that G-CSF is produced in the human follicle shortly before the ovulatory phase and may play an important role in the mechanism of ovulation.     

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.