Tyrosine requirements in children with classical PKU determined by indicator amino acid oxidation

Tyrosine (Tyr) is an essential amino acid in phenylketonuria (PKU) because of the limited hydroxylation of phenylalanine (Phe) to Tyr. The recommended intakes for Tyr in PKU are at least five times the recommended phenylalanine intakes. This suggests that Phe and Tyr contribute approximately 20 and 80%, respectively, of the aromatic amino acid (AAA) requirement (REQ). In animals and normal humans, dietary Tyr was shown to spare 40-50% of the Phe requirement, proportions that reflect dietary and tissue protein composition. We tested the hypothesis that the Tyr REQ in PKU would account for 45% of the total AAA REQ by indicator amino acid oxidation (IAAO). Tyr REQ was determined in five children with PKU by examining the effect of varying dietary Tyr intake on lysine oxidation and the appearance of (13)CO(2) in breath (F(13)CO(2)) under dietary conditions of adequate energy, protein (1.5 g x kg(-1) x day(-1)), and phenylalanine (25 mg x kg(-1) x day(-1)). Lysine oxidation and F(13)CO(2) were determined using a primed 4-h oral equal-dose infusion of L-[1-(13)C]lysine. Lysine oxidation and F(13)CO(2) decreased linearly as Tyr intake increased, to a break point that was interpreted as the mean dietary Tyr requirement (16.3 and 19.2 mg x kg(-1) x day(-1), respectively). At Tyr intakes of >16.3 and 19.2 mg x kg(-1) x day(-1), lysine oxidation and F(13)CO(2), respectively, were low and constant. This represents 40.4 and 44.4%, respectively, of the total AAA intake. The current recommendations for Tyr intake in PKU patients appear to be overestimated by a factor of approximately 5. This study is the first application of the IAAO technique in a pediatric population and in humans with an inborn error of metabolism.     

Phenylalanine requirement in children with classical PKU determined by indicator amino acid oxidation

Dietary restriction of phenylalanine is the main treatment for phenylketonuria (PKU), and current estimates of requirements are based on plasma phenylalanine concentration and growth. The present study aimed to determine more precisely the phenylalanine requirements in patients with the disease by use of indicator amino acid oxidation, with L-[1-13C]lysine as the indicator. Breath 13CO2 production (F 13 CO2) was used as the end point. Finger-prick blood samples were also collected for measurement of phenylalanine to relate phenylalanine intake to blood phenylalanine levels. The mean phenylalanine requirement, estimated using a two-phase linear regression crossover analysis, was 14 mg. kg(-1). day(-1), and the safe population intake (upper 95% confidence interval of the mean) was found to be 19.5 mg. kg(-1). day(-1). A balance between phenylalanine intake and the difference between fed and fasted blood phenylalanine concentration was observed at an intake of 20 mg. kg(-1). day(-1). The similarity between these two values (19.5 and 20 mg. kg(-1). day(-1)) suggests that the maximal phenylalanine intake for children with PKU should be no higher than 20 mg. kg(-1). day(-1).     

Features of cardiovascular functioning during different phases of the menstrual cycle

The purpose of the present study was to determine whether there is a menstrual cycle effect on heart rate, blood pressure and heart rate variability. 10 healthy regularly cycling females (age 19-23 years) were studied during the follicular phase and luteal phase over two month. We found significant changes in heart rate, AMo and stress index during the menstrual cycle with a minimum in the follicular phase and maximum in the luteal phase. The HF and LF components decreased more during the luteal phase than during the follicular phase (p < 0.05), whereas a tendency for increase LF/HF was observed in the luteal phase. In the follicular phase SDNN, pNN50, Mo, MxDMn were significantly higher than in the luteal phase. Furthermore, the VIK was higher in the luteal phase compared to the follicular phase (p = 0.003). Blood pressure did not show any significant change during both these phases of the menstrual cycle. These findings indicate that sympathetic nervous activity in the luteal phase is greater than in the follicular phase, whereas parasympathetic nervous activity is predominant in the follicular phase. A difference of the balance of ovarian hormones may be responsible for these changes of autonomic functions during the menstrual cycle.     

Plasma insulin and glucagon concentrations and biochemical variables in regularly menstruating females with ovulatory and anovulatory menstrual cycles.

Ovarian hormones are known to affect endocrine pancreas function. However, data concerning the effects of anovulatory menstrual cycles in regularly menstruating women on endocrine pancreas and blood metabolites are lacking. We examined plasma insulin, glucagon, glucose, lactate, urea and glycerol concentrations in reproductive-age, regularly menstruating females classified as ovulating or non-ovulating on the basis of basal body temperature measurements and plasma 17beta-estradiol and progesterone determinations. All measurements were performed twice--in the follicular and again in the luteal phases of the menstrual cycle. There were no differences in plasma lactate and glycerol concentrations between the two groups of subjects. Plasma insulin concentrations tended to be lower in non-ovulating than in ovulating women. In addition, plasma glucagon did not differ in the follicular (33.2 pmol/l) or luteal phase of the menstrual cycle in females with disturbed ovarian hormone secretion (34.1 pmol/l). In contrast, plasma glucagon concentrations in the luteal phase (32.8 pmol/l) were significantly higher than in the follicular phase (24.9 pmol/l) of the menstrual cycle in ovulating women. Plasma glucose concentrations in the follicular phase of the menstrual cycle in non-ovulating women (4.1 mmol/l) were slightly but significantly lower than in their ovulating counterparts (5.3 mmol/l). Furthermore, no correlations were noted between plasma glucose and insulin-to-glucagon molar ratio in non-ovulating subjects. Plasma urea concentrations in non-ovulating women were markedly lower than in ovulating women in both follicular and luteal phases of the menstrual cycle (4.1 and 3.9 mmol/l vs. 5.3 and 5.4 mmol/l in non-ovulating and ovulating women, respectively). In ovulating women, plasma urea levels in both cycle phases were significantly correlated with plasma glucagon concentrations, but no such correlation was found in non-ovulating women. In conclusion, anovulatory menstrual cycles in premenopausal females slightly altered pancreatic hormone plasma levels but markedly impaired their action on plasma glucose and urea concentrations.     

CO2 sensitivity changes during the menstrual cycle

A study of the changes in CO2 sensitivity at rest was undertaken in 20 regularly menstruating females in an attempt to determine the influence of the menstrual cycle on this variable. A biphasic oral temperature graph was used to signify fertility and demarcate three phases of the cycle. A CO2-rebreathing test was conducted 3 times/wk for 6 wk to obtain CO2 sensitivity and CO2 threshold measures. An analysis of variance was used to compare the results collected in each phase of the cycle for each of the variables. A significant increase was found in the sensitivity to CO2 between the follicular and luteal phases, a significant decrease between the luteal and menstrual phases, and no significant difference between the follicular and menstrual phases. The change between follicular and luteal phases was attributed to the effect of progesterone, which is elevated during the luteal phase. No significant change was found in the CO2 threshold level.     

Relationship among the status of the human oocyte, the 17 beta-estradiol concentration in the antral fluid and the follicular size

We studied the relationship among the status of the human oocytes, the E2 concentration in the antral fluid and the follicular size in the different phases of the menstrual cycle, in order to determine the microenvironment of the follicles with healthy or degenerative oocytes in the human ovary. In the follicular phase of the menstrual cycle, follicles which contained a healthy but not degenerative oocyte had a significantly higher level of 17 beta-estradiol (E2). In the late follicular phase, the larger follicles (greater than or equal to 13 mm, in diameter) had only health oocytes. It seems that the follicle containing a degenerative oocyte does not develop physiologically until maturation of the preovulatory follicle. In the luteal phase, there were no relationships among the status of the oocyte, E2 concentration in the antral fluid and the follicular size. However, the E2 levels of the antral follicles with healthy oocytes in an ovary with corpus luteum were significantly lower than those in the contralateral ovary. The results suggest that the corpus luteum may exert an influence on the adjacent follicles.     

月经周期对女性睡眠-觉醒和静息-活动的影响

目前有关月经周期对睡眠影响的研究结果并不一致,而对月经周期中昼夜睡眠-觉醒及静息-活动节律尚缺乏系统性的研究.本研究旨在观察正常育龄期女性月经周期中睡眠-觉醒及静息-活动昼夜节律的变化.我们采用静息-活动监测仪(actigraphy)和睡眠日志,调查了12个自然生活状态下健康育龄期妇女在月经周期不同阶段,即行经期、围排卵期、黄体早期及黄体晚期中睡眠与活动节律的变化.结果显示,睡眠-觉醒节律参数在四期之间无统计学显著差异;而静息-活动节律方面,所有受试女性静息-活动节律的平均日周期长度为(24.01±0.29)h,并且四期之间无显著性差异.行经期日间稳定系数(interdaily stability,IS)比黄体早期显著增加(P＜0.05).黄体早期日间活动开始时间明显较黄体晚期提前(P＜0.05);黄体早期的活动峰值时相比围排卵期显著提前(P＜0.05).月经周期可以影响静息-活动昼夜节律时相.而总体静息-活动数量与质量未发生显著变化;健康育龄期妇女在月经周期的各阶段中睡眠-觉醒节律亦无明显变异.     

Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women

AIM: The aim of this study was to investigate the effect of baclofen administration on growth hormone (GH) secretion during different phases of the menstrual cycle. METHODS: Twelve healthy women (33.6 +/- (SD) 2.8 years; range 23-40 years) with regular menstrual cycles were enrolled. The phases of the menstrual cycle were determined using transvaginal ultrasonography (TV-US) and detecting hormonal serum levels. Plasma GH levels were evaluated during the early follicular, periovulatory and luteal phases of the cycle before and after the baclofen challenge test. RESULTS: After acute baclofen administration, GH levels increased significantly (p < 0.001) compared to basal values during the periovulatory and luteal phases, while no significant variation was detected during the early follicular phase. In addition, plasma GH levels resulted significantly (p < 0.001) higher during the luteal phase than during the periovulatory phase. CONCLUSION: Acute baclofen administration induces a significant increase in plasma GH levels in healthy females during the periovulatory and luteal phases, but not during the early follicular phase. These data suggest a modulator role of plasma sex steroids levels on GH release induced by baclofen.     

Cardiovascular reactivity to mental stress: relationship with menstrual cycle and gender

The purpose of the present study was to determine the fluctuation in cardiovascular reactivity to mental stress during the menstrual cycle by comparing heart rate variability (HRV), and other physiological and psychological data in females with those in males. Cardiovascular reactivity to two mental tasks was measured in 14 females during the follicular and luteal phase of menstruation over two menstrual cycles. The same tasks were subsequently given to a matched pair of males (N=14), at the same intervals as their corresponding females. Heart rate, blood pressure and HRV were used as indices of cardiovascular reactivity. Subjective mental workload was measured at the end of each task. Power spectral analysis of HRV showed that the high frequency (HF) component in HRV decreased more during the luteal phase than the follicular phase. The low frequency (LF) component in HRV and the LF/HF ratio in the luteal phase were significantly higher than that in the follicular phase. The LF component and the LF/HF ratio were significantly lower in females than in males; conversely, the HF component was significantly higher in females than in males. Neither significant effects of menstrual cycle, gender and mental stress nor any significant interactions were found for mental workload. These findings indicate that sympathetic nervous activity in the luteal phase is significantly greater than in the follicular phase whereas parasympathetic nervous activity is predominant in the follicular phase. The results also suggest that predominance of sympathetic nervous activity in males compared with a dominant parasympathetic nervous activity in females.     

Influence of the menstrual cycle on the LPS-induced cytokine response of monocytes

We previously observed a gender difference in the cytokine response of peripheral blood monocytes (PBM). The study was performed to find out whether the gender-related difference might be due to hormonal changes during the menstrual cycle in healthy premenopausal females. The release of tumour necrosis factor a (TNF-alpha) was reduced in the premenopausal females during the luteal phase compared to the follicular phase. Compared to the male controls the release of TNF-alpha and of interleukin 6 (IL-6) during the luteal phase was also diminished. In premenopausal females the concentration of estradiol in plasma correlated with the release of TNF-alpha and IL-6 during the luteal phase.     

Pathogen disgust,but not moral disgust,changes across the menstrual cycle

The Compensatory Prophylaxis Hypothesis (CPH) proposes that during periods of increased susceptibility to infections, e.g., during the luteal phase of the menstrual cycle when progesterone suppresses immune function, women should feel more disgust toward pathogen cues and behave prophylactically. We investigate differences in disgust sensitivity and contamination sensitivity during different phases of the menstrual cycle in regularly cycling, healthy 93 rural and urban Polish women using the within-subject design. Disgust sensitivity was measured during two different phases of a menstrual cycle: 1) the follicular phase (the 5th or 6th day of the cycle) and 2) the luteal phase (on the 5th day after a positive ovulatory test or on 20th day of a cycle if the result of the ovulatory test was not positive). In the luteal phase, women scored higher on the Pathogen Disgust of the Three-Domain Disgust Scale, the Contamination Obsessions and Washing Compulsions Subscale of Padua Inventory, and on ratings of photographs showing sources of potential infections than in the follicular phase. Moral Disgust of the Three-Domain Disgust Scale did not differ between cycle phases. Hence, results suggest that women feel more disgusted toward cues to pathogens during the luteal phase, when susceptibility to infection is greater. We suggest that it is necessary to incorporate ovulatory testing as well as to conduct repeated measurements of disgust sensitivity in future tests of the CPH. Moreover, we believe that understanding how the feeling of pathogen disgust varies across the menstrual cycle and in relation to progesterone levels could be useful in designing effective infectious diseases prevention strategies for women.     

Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise

To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia.     

Total branched-chain amino acids requirement in patients with maple syrup urine disease by use of indicator amino acid oxidation with L-[1-13C]phenylalanine

Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by defects in the mitochondrial multienzyme complex branched-chain alpha-keto acid dehydrogenase (BCKD; EC 1.2.4.4), responsible for the oxidative decarboxylation of the branched-chain ketoacids (BCKA) derived from the branched-chain amino acids (BCAA) leucine, valine, and isoleucine. Deficiency of the enzyme results in increased concentrations of the BCAA and BCKA in body cells and fluids. The treatment of the disease is aimed at keeping the concentration of BCAA below the toxic concentrations, primarily by dietary restriction of BCAA intake. The objective of this study was to determine the total BCAA requirements of patients with classical MSUD caused by marked deficiency of BCKD by use of the indicator amino acid oxidation (IAAO) technique. Five MSUD patients from the MSUD clinic of The Hospital for Sick Children participated in the study. Each was randomly assigned to different intakes of BCAA mixture (0, 20, 30, 50, 60, 70, 90, 110, and 130 mg.kg(-1).day(-1)), in which the relative proportion of BCAA was the same as that in egg protein. Total BCAA requirement was determined by measuring the oxidation of l-[1-(13)C]phenylalanine to (13)CO(2). The mean total BCAA requirement was estimated using a two-phase linear regression crossover analysis, which showed that the mean total BCAA requirement was 45 mg.kg(-1).day(-1), with the safe level of intake (upper 95% confidence interval) at 62 mg.kg(-1).day(-1). This is the first time BCAA requirements in patients with MSUD have been determined directly.     

Long-term data on basic reproductive parameters and evaluation of endocrine,morphological, and behavioral measures for monitoring reproductive status in a group of semifree-ranging Tonkean macaques (Macaca tonkeana)

Cycle and gestation lengths, menstruation patterns, female genital swelling characteristics, and male-female consortship durations are reported in a semifree-ranging group of Tonkean macaques (Macaca tonkeana) studied over a 12 year period. In addition, profiles of urinary estrone conjugates (E1C) and immunoreactive pregnanediol glucuronide (PdG) throughout four complete menstrual cycles in two females and three full-term pregnancies are presented. Based on intermenstrual intervals, a mean cycle length of 37–41 days (n = 55 cycles in 10 females) was found. Gestation length averaged 173 days (n = 27 pregnancies in eight females). Measurement of PdG immunoreactivity in urine revealed a cyclic pattern with a 5–15-fold increase between follicular and luteal phase concentrations, suggesting that PdG is a reliable indicator of ovarian cyclicity and luteal function. In contrast to PdG, E1C excretion showed no clear pattern throughout the cycle; however, highest values of E1C were usually found shortly before the onset of the luteal phase PdG rise at the presumed time of ovulation. Levels of both hormones were elevated during the first half of gestation and showed a marked increase throughout the second half, with maximum E1C concentrations being up to 100-fold higher than nonpregnant levels. Consortships by the male and occurrence of female genital swelling were long lasting (on average 5–10 days and 13 days, respectively) and were restricted to the follicular phase of the cycle. The day of maximal swelling and day of detumescence as well as the end of male consortship were closely associated with the periovulatory period. Swellings and consortships were longer following lactational ammenorhea than for subsequent cycles. The evolutionary significance of the cyclical changes undergone by females upon their relations with males is discussed. © 1996 Wiley-Liss, Inc.     

Non-Advertized does not Mean Concealed: Body Odour Changes across the Human Menstrual Cycle

Females of a number of primate species display their fertile period by behavioural and/or morphological changes. Traditionally, the fertile period in human females has been considered to be concealed. However, this presumption has rarely been tested. One of the possible mechanisms for assessing menstrual cycle phase is through the sense of smell. In this study possible changes in odour across the menstrual cycle were investigated. Samples of body odour were acquired from 12 women (aged 19–27 yr), none of whom were using hormonal contraceptives. Samples were collected using cotton pads worn in the armpit for 24 h, from the menstrual, follicular and luteal cycle phases. Our experimental sample of 42 males (age 19–34 yr) repeatedly rated these odour samples for their intensity, pleasantness, attractiveness and femininity. Raw subjective smell ratings from each man were transformed to z‐scores. Subsequently, these z‐scores were tested by the general linear mixed‐model analysis (PROC MIXED, SAS) with the female's ID nested within the subject's ID as a random factor to account for the repeated measures of the subjects. Significant changes across the cycle were found for ratings of pleasantness [F_(2,689) = 702; p = 0.001], attractiveness [F(2,546) = 6.35; p = 0.002] and intensity [F(2,530) = 3.57; p = 0.028]. Odour from women in the follicular (i.e. fertile) phase was rated as the least intense and the most attractive. Subsequent post hoc analysis revealed significant differences in intensity, pleasantness and attractiveness between the menstrual phase and the follicular phase, and in pleasantness and attractiveness between the menstrual and luteal phases. Significant difference between the follicular and the luteal phase was found only for attractiveness. Our results suggest that men can potentially use smell as a mechanism for monitoring menstrual cycle phase in current or prospective sexual partners. Therefore, the fertile period in humans should be considered non‐advertized, rather than concealed.     

Effect of enucleation of the corpus luteum at different stages of the luteal phase of the human menstrual cycle on subsequent follicular development

To investigate the mechanism of suppression of follicular development during the luteal phase of the human menstrual cycle, the corpus luteum was enucleated surgically from 10 women at various times after ovulation. In the 24 h after CL enucleation there was an immediate and rapid fall in the concentration of oestradiol and progesterone and a temporary decline in the concentration of FSH and LH. Within 3 days, however, all 10 women showed evidence of renewed follicular activity as indicated by a progressive rise in the concentration of oestradiol. This rise was preceded by a rise in the concentration of FSH and LH, and ovulation, as indicated by a mid-cycle surge in LH and rise in the concentration of plasma progesterone, occurred 16-19 days after enucleation. There was no significant difference in the time to ovulation following enucleation at different times of the luteal phase. The post-operative follicular phase, measured from the time of enucleation, was 3 days longer than that observed pre-operatively from the first day of menstrual bleeding. In the follicular phase of post-operative cycles the concentration of FSH was higher and that of oestradiol lower than the corresponding values before surgery. These results indicate that the absence of healthy antral follicles in the luteal phase of the cycle is due to the inhibitory effects of the corpus luteum. The fact that, after CL enucleation, emergence of the dominant follicle was always preceded by a rise in the concentration of FSH and LH suggests that suppression of gonadotrophins by ovarian steroids secreted by the corpus luteum is responsible for the inhibition of follicular development during the luteal phase of the cycle.     

月经周期不同阶段游离皮质醇昼夜节律的变化

为了研究皮质醇分泌的昼夜节律在月经周期中的变化,实验对15位月经周期正常的育龄期健康妇女,在月经周期的不同阶段分别于24h内每隔两小时采样,检测唾液昼夜游离皮质醇水平。采用非线性回归分析模型分析皮质醇昼夜节律。结果显示,皮质醇昼夜节律在整个月经周期都具有复杂的明显受到亚节律(ultradian)影响的分泌形式;与月经期相比,围排卵期和黄体晚期昼夜节律波峰宽度(peak-width)明显减低(P=0．005与0．031),而昼夜节律波谷(trough)有抬高趋势(P=0．0622与0．066);黄体晚期的亚节律波幅(ultradian amplitude)与月经期相比显著减低(P=0．002)而与围排卵期相比有减低趋势(P=0．05)。这些结果提示月经周期的不同阶段对皮质醇分泌的昼夜节律有影响。     

Resting metabolic rate and thermic effects of a sucrose-sweetened soft drink during the menstrual cycle in young Chinese women.

The resting metabolic rate (RMR) and thermic effects (TEF) of a sucrose-sweetened soft drink in a group (n = 19) of ovulating young Chinese women were determined by indirect calorimetry in the midfollicular and midluteal phases of the menstrual cycle. Urinary luteinizing hormone surge was used to confirm ovulation. The RMR was measured twice in each phase and found to be similar (F(1,18) = 0.863) across the follicular (5018 kJ/24 h) and the luteal (5098 kJ/24 h) phases. Within each phase and on separate days, subjects were given water (280 mL) or sucrose-sweetened soft drink (539 kJ). Soft drink, but not water, consumption increased energy expenditure over a period of 45 min. Compared with the follicular phase, a small but significant increase in TEF (kJ/45 min) was observed in the luteal phase (t = 2.434, p < 0.05). Energy expenditure after drinking the soft drink, however, was similar in the two phases. RMR was positively correlated with TEF (r = 0.613, p < 0.01) and net TEF (r = 0.648, p < 0.005) in the luteal but not the follicular phase. In ovulating women, the thermic effect of sucrose is influenced by the phase of the menstrual cycle.     

Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle.

The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle.     

Pain sensations to the cold pressor test in normally menstruating women: comparison with men and relation to menstrual phase and serum sex steroid levels

The role of gonadal hormones on pain sensations was investigated in normally menstruating women (n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a 4-wk period, and serum concentrations of 17beta-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase, and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men (n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity, demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol. While no statistically significant sex differences in pain measurements were found, women displayed much more pronounced, and statistically significant, session-to-session effects than men, with increased pain threshold and decreased pain intensity with each test session. Hence, these data suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation and show that adaptation to the cold pressor test may be sex dependent.