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.     

Cyclical changes in endogenous overnight creatinine clearance during the third trimester of pregnancy

To investigate the pattern of change in endogenous overnight creatinine clearance during the third trimester, 12 healthy women with uncomplicated pregnancies were examined three times a week. Urine was collected overnight from 22.00 to 08.00 hours and analysed for creatinine. Serum was sampled in the morning and analysed for creatinine, beta 2-microglobulin, progesterone and estradiol. The general trend of creatinine clearance was parabolic with a declining level during the last month before term. A sinusoid pattern with minimum values around the time when the women would have had menstruation had they not become pregnant was superimposed on the parabolic trend. A mathematical model (parabolas overlaid with a cosine curve) was constructed and fitted to the data. The cyclical pattern was significant. Serum creatinine showed a pattern with increasing values during the last 4-6 weeks before term and cyclical changes which were also significant. In the individual case the monthly and preterm clearance decrement sometimes was over 50%. Monthly and preterm decreases in creatinine clearance may be quite normal and serial measurements of creatinine clearance are therefore necessary to determine if declining values indicate pathological falls in the glomerular filtration rate.     

The excretion of urea by dogs following a meat meal.

1. After a meal of meat (10g/kg), urea excretion in dogs increased by about 200%, plasma urea by 60% and exogenous creatinine clearance by 40% in comparison with control experiments. 2. Urea, given by stomach tube in doses producing the same increase in plasma urea, caused urea excretion to increase by only 90%, with no increase in creatinine clearance. With the increased glomerular filtration rate after meat there was added excretion of urea. 3. In control experiments and after urea, the rate of excretion of urea was directly proportional to plasma urea. The ratio urea clearance/creatinine clearance, was 0-45. 4. After meat, urea clearance increased more than creatinine clearance, the ratio increasing to 0-55, i.e. a smaller fraction of the filtered urea was re-absorbed after meat. 5. After meat, 10g/kg, the rate of urea production rose to 230-600 mumole/min for 4-6 hr.     

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.     

Gustatory changes associated with the menstrual cycle.

We studied changes in the palatability and gustatory functions as they correlate with the menstrual cycle in 30 healthy females with regular menstrual cycles. The gustatory function was investigated by conducting electrogustometry and by the filter-paper disk method with taste solutions in the follicular and luteal phases of the same subjects. The responses to a questionnaire revealed that appetite was enhanced prior to menstruation in 14 cases (46.7%). The results of electrogustometry showed that the threshold in the domain of the chorda tympani nerve was 0.3 +/- 3.4 dB in the follicular phase and -0.9 +/- 2.8 dB in the luteal phase. Although the threshold in the luteal phase indicated a statistically significant decrease (p < 0.05), the difference was so small that the change could not be subjectively discriminated. The threshold in the domain of the glossopharyngeal nerve was 2.6 +/- 4.0 dB in the follicular phase and 1.7 +/- 3.9 dB in the luteal phase, with no significant difference between the two values. Gustatory thresholds as obtained by the filter-paper disk testing were not significantly different between the follicular and luteal phases. Thus, although the taste function may change through the menstrual cycle, changes in gustatory thresholds are minimal and remain within the normal range.     

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.     

Renal function and digoxin clearance during quinidine therapy

To investigate further the handling of digoxin by the kidneys during quinidine therapy, clearances of digoxin, 51Cr-EDTA, PAH and endogenous creatinine were measured together with beta 2-microglobulin in the urine before and during quinidine therapy in 10 patients on maintenance digoxin therapy. Renal clearance of digoxin (corrected for 30% plasma binding) decreased on the average by 55% (137 +/- 73 to 73 +/- 25 ml/min, mean +/- SD). The steady state plasma concentration of digoxin increased more than twofold (1 . 0 +/- 0 . 34 to 2 . 5 +/- 0 . 79 nmol/L, mean +/- SD). The clearances of 51Cr-EDTA and PAH were not altered during quinidine therapy, indicating that neither glomerular filtration nor total renal blood flow changed when quinidine was added. The ratio of the renal clearance of unbound digoxin to that of the glomerular filtration rate was above one for all 10 patients before quinidine, indicating the involvement of tubular secretion in the renal elimination of digoxin. After the administration of quinidine this ratio decreased in all patients (from 1 . 51 +/- 0 . 30 to 0 . 83 +/- 0 . 38, mean +/- SD). Some patients had ratios well below one suggesting re-absorption of digoxin. Beta 2-microglobulin excretion was unchanged during treatment with quinidine. It is concluded that a significant portion of the renal elimination of digoxin in man results from tubular secretion and that this excretory mechanism is inhibited by quinidine.     

Renal contribution to acid-base regulation during the menstrual cycle

Menstruating women exhibit a light but sustained hypocapnia during the luteal phase. To elucidate whether the hypocapnia results primarily from a respiratory or renal mechanism, we measured the rate of urinary excretion of acid at intervals during the menstrual cycle in five subjects. The acid-base composition of arterial blood in three subjects and end-tidal PCO2 in the remaining two subjects were also determined. During the follicular phase, the acid-base composition of blood and the rate of net acid excretion remained virtually constant. After ovulation, significant decreases in PaCO2 (3.5 mmHg), [HCO3]p (2 meq/liter), and net acid excretion (2 meq/h) occurred in the first 4-6 days of the luteal phase (14 days long). Following this, net acid excretion returned to the preovulatory level. PaCO2 and [HCO3]p, however, remained decreased for 3 more days. At the end of the luteal phase, restoration of PaCO2 proceeded faster than that of [HCO3]p. The acid-base changes in blood and urine observed during the luteal phase were comparable to those occurring during adaptation and recovery from sustained hypocapnia, suggesting that hypocapnia during the luteal phase is primarily respiratory in origin.     

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.     

Time sense for short intervals during the follicular and luteal phases of the menstrual cycle in humans

The present study investigated if the time sense (using short intervals) was influenced by the phase of the menstrual cycle. Fourteen women (age: 21.8+/-1.3 years, height: 158.1+/-4.6 cm, body weight: 50.9+/-3.2 kg, mean+/-S.D.) were examined. Their menstrual phase was checked by the participants themselves prior to the study, by measuring oral temperatures after waking but while still in bed over the course of 1-2 months. Participants entered a climatic chamber (26 degrees C, 60% RH, 200 lx) at 09:00 h during either the follicular or luteal phase, and sat quietly on a sofa for 4 h before performing the time sense tests. These used intervals ranging from 1 to 60 s, and consisted of time estimation and time production. In the time estimation test, the participant was required to estimate the interval between two signals provided by buzzers; 10 random intervals were given. For the time production test, the participant was required to produce the interval displayed on a screen by pushing the space key of a computer twice; 10 random intervals were given. The order of testing during the follicular and luteal phases, and of performing the time estimation and time production tests, was counterbalanced. The results indicate that the time sense ran significantly faster during the luteal phases. The findings are discussed in terms of a higher load error between the actual core temperature and its thermoregulatory set-point during the luteal phase of the menstrual cycle.     

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.     

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.     

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 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 serum concentrations of growth hormone, insulin, insulin- like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle, with significantly higher values in the luteal phase compared to the proliferative phase (P < 0.001). Mean individual variation in IGF-I concentrations throughout the menstrual cycle was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations between the luteal and the proliferative phases. Mean individual variation in IGFBP- 3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7; range 3.2-14.1). IGFBP-1 concentrations were inversely associated with insulin concentrations, and showed a significant pre-ovulatory increase that returned to baseline at the day of the LH surge. Fasting insulin concentrations showed large fluctuations throughout the menstrual cycle without any distinct cyclic pattern. No cyclic changes in urinary GH excretion during menstrual cycle were detected. We conclude that, although IGF-I concentrations are dependent on the phase of the menstrual cycle, the variation in IGF-I concentrations throughout the menstrual cycle is relatively small. Therefore, the menstrual cycle does not need to be considered when evaluating IGF-I or IGFBP-3 serum values in women suspected to have GH deficiency.      

Mental stress‐induced haemoconcentration in women: Effects of menstrual cycle phase

Objectives In women, variation in the incidence of myocardial infarction (MI) has been reported with phase of the menstrual cycle. Mental stress‐induced rheological and haemodynamic perturbations have been implicated in the triggering of MI. This study examined cardiovascular reactions to mental stress across the menstrual cycle, as a factor contributing to the known variation between the menstrual cycle phases in MI incidence. Methods Rheological and haemodynamic activity during rest and a prolonged mental stress task were assessed in 12 women during the follicular and luteal phases of the menstrual cycle. Results The stress task increased haematocrit, colloid osmotic pressure, blood pressure and heart rate, and decreased heart rate variability and R‐wave to pulse interval. However, there were no effects of menstrual phase on rheological or haemodynamic function at rest or in response to mental stress. There were also no moderating menstrual cycle effects for the rheological or haemodynamic reactions over time to this prolonged stress task. Conclusions Our findings do not support the hypothesis that variations in reactions to mental stress can explain the reported variations in risk for MI across the menstrual cycle.     

Assessment of changes in volume and vascularity of the ovaries during the normal menstrual cycle using three-dimensional power Doppler ultrasound

BACKGROUND: Our aim was to describe changes in the volume and vascularization of both ovaries, the dominant follicle and the corpus luteum during the normal menstrual cycle using three-dimensional (3D) power Doppler ultrasound. METHODS: Fourteen healthy volunteers underwent serial transvaginal 3D ultrasound examinations of both ovaries on cycle day 2, 3 or 4, then daily from cycle day 9 until follicular rupture and 1, 2, 5, 7 and 12 days after follicular rupture. The volume and vascular indices of the ovaries, the dominant follicle and the corpus luteum were calculated off-line using virtual organ computer-aided analysis (VOCAL) software. RESULTS: The volume of the dominant ovary increased during the follicular phase, decreased after follicular rupture and then increased again during the luteal phase. Vascular indices in the dominant ovary and the dominant follicle/corpus luteum increased during the follicular phase, the vascular flow index (VFI) in the dominant follicle being on average (median) 1.7 times higher on the day before ovulation than 4 days before ovulation (P=0.003). The vascular indices continued to rise after follicular rupture so that VFI in the corpus luteum was on average (median) 3.1 times higher 7 days after ovulation than in the follicle on the day before ovulation (P=0.0002). The volume and vascular indices in the non-dominant ovary manifested no unequivocal changes during the menstrual cycle. CONCLUSIONS: Substantial changes occur in volume and vascularization of the dominant ovary during the normal menstrual cycle. 3D power Doppler ultrasound may become a useful tool for assessing pathological changes in the ovaries, for example, in subfertile patients.     

Serum fluctuations of total and free tryptophan levels during the menstrual cycle are related to gonadotrophins and reflect brain serotonin utilization

BACKGROUND: Serotoninergic (5-HT) neurons are suggested to regulate estrous cycle in animal models. In the present study we evaluated whether a relationship exists between the serotoninergic precursors in the central nervous system and the gonadotrophin-ovarian cyclic function. METHODS: We measured 5-HT precursors [free (FT) and total (TT) tryptophan] and LH, FSH and 17beta-estradiol (E2) levels in the serum of 15 fertile women with normal menstrual cycles during the follicular (cycle days 1-5, 7-11), mid-cycle (cycle days 14-16) and luteal (cycle days 17-19, 22-24) phases. RESULTS: TT and FT were significantly increased in the 7-11 and 17-19 cycle days and were decreased at mid-cycle (P < 0.01), with a cyclic and opposite behaviour when compared to that of FSH and LH. Indeed, correlation analysis through the matrix of mean values showed that LH was negatively correlated to TT (r = -0.636) and FT (r = -0.574), as well as FSH (TT, r = -0.655; FT, r = -0.663), and that TT and FT were positively correlated to each other (r = 0.801; P < 0.001). Furthermore, whilst the two FT peaks reached approximately the same levels in the follicular and luteal phase, TT levels were approximately 30% higher in the luteal than in the follicular phase of the cycle: thus in the first (follicular) phase FT peak was relatively higher than that of TT, whereas the contrary occurred in the second (luteal) phase of the cycle. CONCLUSIONS: Both TT and FT levels have cyclic variations throughout the menstrual cycle, being lowest at mid-cycle (14-16 cycle days), concomitant with the highest LH and FSH concentrations, and higher before and after mid-cycle phase, coinciding with the lowest circulating LH/FSH levels. Since TT and FT levels in the plasma have cyclic changes, our study: (i) suggests that a consumption of serum serotonin precursors takes place concomitant with gonadotrophin release during menstrual cycle; (ii) may represent an in vivo model to investigate this relationship in women in different physiopathological conditions.     

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.     

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.