Influence of cold, exercise, and caffeine on catecholamines and metabolism in men

Recently we found that caffeine ingestion did not enhance either thermal or fat metabolic responses to resting in cold air, despite an increase in plasma epinephrine and free fatty acids. Theophylline, another methylxanthine, has been shown to be effective during exercise but not at rest during cold stress. Therefore we hypothesized that caffeine ingestion before exercise in cold air would have a thermal-metabolic impact by increasing fat metabolism and increasing oxygen consumption. Young adult men (n = 6) who did not normally have caffeine in their diet performed four double-blind trials. Thirty minutes after ingesting placebo (dextrose, 5 mg/kg) or caffeine (5 mg/kg) they either exercised (60 W) or rested for 2 h in 5 degrees C air. Cold increased (P less than 0.05) plasma norepinephrine while both caffeine and exercise increased (P less than 0.05) epinephrine. Serum free fatty acids and glycerol were increased, but there were no differences between rest and exercise or placebo and caffeine. Caffeine had no influence on either respiratory exchange ratio or oxygen consumption either at rest or during exercise. The exercise trials did not significantly warm the body, and they resulted in higher plasma norepinephrine concentrations and lower mean skin temperatures for the first 30 min. The data suggest that skin temperature stimulates plasma norepinephrine while caffeine has little effect. In contrast, caffeine and exercise stimulate plasma epinephrine while cold has minimal effect. Within the limits of this study caffeine gave no thermal or metabolic advantage during a cold stress.     

The effects of substrate utilization, manipulated by caffeine, on post-exercise oxygen consumption in untrained female subjects

The effect of substrate utilization manipulated by caffeine on post-exercise oxygen consumption was investigated in five untrained females (age = 21 +/- 1.5 years), following 90 min of treadmill walking at 55% maximal oxygen consumption. Each subject participated in the two trials (control and experimental) within 2 weeks of each other. Immediately following the measurement of resting oxygen consumption, subjects consumed one of the two test beverages 60 min prior to exercise: 5 mg of caffeine per kg of body-weight in 200 ml of orange juice (CA) or 200 ml of orange juice (C). Assignment of CA and C was made in a random, double blind fashion. Immediately prior to the exercise phase (0 min) resting oxygen consumption was again measured. Following exercise, subjects returned to the same pre-exercise sitting position where respiratory data was collected over 1 h. No significant differences were found in resting oxygen consumption and respiratory exchange ratio (R) prior to caffeine ingestion (-60 min). One hour after caffeine ingestion (0 min) oxygen consumption and free fatty acid (FFA) levels increased significantly compared to C. During and 1 h following exercise, oxygen consumption and FFA levels were significantly greater, with R values being significantly lower in CA compared to C. These findings provide further evidence that metabolic substrate is somehow implicated in elevating oxygen consumption following exercise cessation.     

Tendon collagen synthesis at rest and after exercise in women.

In general, there is a higher incidence of musculoskeletal injuries during physical activity in women than in men. We hypothesized that in women rates of tendon collagen synthesis would be lower than in men at rest and after exercise, especially in the later luteal phase when estrogen and progesterone concentrations are higher than the early follicular phase. We studied tendon collagen fractional synthesis rate (FSR) in 15 young, healthy female subjects in either the early follicular (n = 8) or the late luteal phase (n = 7) 72 h after an acute bout of one-legged exercise (60 min kicking at 67% workload maximum) (72 h) and compared the results with those previously obtained for men. Samples were taken from the patellar tendon in both the exercised and rested legs to determine collagen FSR by the incorporation of [15N]proline into tendon collagen hydroxyproline. There was no effect of menstrual phase on tendon collagen synthesis either at rest or after exercise. However, there was a significant difference between women and men at rest (women = 0.025 +/- 0.002%/h, men = 0.045 +/- 0.008%/h; P < 0.05) and 72 h after exercise (women = 0.027 +/- 0.005%/h; men = 0.058 +/- 0.008%/h). Furthermore, rest and 72-h tendon collagen synthesis were not different in women, whereas in men tendon collagen synthesis remained significantly elevated 72 h after exercise. It is concluded that both in the resting state and after exercise, tendon collagen FSR is lower in women than in men, which may contribute to a lower rate of tissue repair after exercise.     

The effects of two levels of caffeine ingestion on excess postexercise oxygen consumption in untrained women

The effects of two levels of caffeine ingestion (5 mg.kg-1, CAF1, and 10 mg.kg-1, CAF2) on postexercise oxygen consumption was investigated in six untrained women aged 20.5 (SEM 0.5) years. After a test to determine maximal oxygen consumption (VO2max) each subject underwent three test sessions at 55% VO2max either in a control condition (CON) or with the CAF1 or CAF2 dose of caffeine. During exercise, oxygen consumption was found to be significantly higher in the CAF1 and CAF2 trials, compared to CON (P < 0.05). During the hour postexercise, oxygen consumption in CAF1 and CAF2 remained significantly higher than in CON (P < 0.05). At all times throughout the exercise, free fatty acid (FFA) concentrations were significantly higher in the caffeine trials than in CON. The FFA concentrations 1 h postexercise (+60 min) were further elevated above resting values for all three trials. Caffeine ingestion caused the greatest elevation above resting levels being 1.89 (SEM 0.19) mmol.l-1 and 1.96 (SEM 0.22) mmol.l-1 for the CAF1 and CAF2 trials, respectively. This was significantly higher (P < 0.0001) than the CON level which was 0.97 (SEM 0.19) mmol.l-1. Respiratory exchange ratio (R) values became significantly lower (P < 0.05) in CAF1 and CAF2 compared to CON at the onset of exercise and continued to decrease during the activity. Throughout the recovery period, R values were significantly lower for both caffeine trials compared to CON. The results of this study would suggest that caffeine is useful in significantly increasing metabolic rate above normal levels in untrained women during, as well as after, exercising at 55% VO2max.     

Influence of altitude and caffeine during rest and exercise on plasma levels of proenkephalin peptide F

The purpose of this study was to examine the resting and exercise response patterns of plasma Peptide F immunoreactivity (ir) to altitude exposure (4300 m) and caffeine ingestion (4 mg.kg b.w.-1). Nine healthy male subjects performed exercise tests to exhaustion (80-85% VO2max) at sea level (50 m), during an acute altitude exposure (1 hr, hypobaric chamber, 4300 m) and after a chronic (17-day sojourn, 4300 m) altitude exposure. Using a randomized, double-blind/placebo experimental design, a placebo or caffeine drink was ingested 1 hour prior to exercise. Exercise (without caffeine) significantly (p less than 0.05) increased plasma Peptide F ir values during exercise at chronic altitude only. Caffeine ingestion significantly increased plasma Peptide F ir concentrations during exercise and in the postexercise period at sea level. Conversely caffeine ingestion at altitude resulted in significant reductions in the postexercise plasma Peptide F ir values. The results of this study demonstrate that the exercise and recovery response patterns of plasma Peptide F ir may be significantly altered by altitude exposure and caffeine ingestion. These data support further study examining relationships between Peptide F (and other enkephalin-containing polypeptides) and epinephrine release in response to these types of physiological stresses.     

Effect of acute or chronic administration of caffeine on performance and on catecholamines during maximal cycle ergometer exercise

Seven men were studied during maximal cycle ergometer exercise, to assess the effects of a single or continuous caffeine ingestion on performance and catecholamine secretion. A single blind and randomised procedure was followed with three trials at 100 +/- 5% VO2 max until exhaustion. The first trial was performed after a single administration of 250 mg of caffeine (a). The second and third trials were performed after a treatment of 5 days with 250 mg caffeine per day (continuous = c) and after placebo (p). a and c caffeine administration, 60 min prior to exercise, did not significantly change the time to exhaustion, but increased the plasma levels of both epinephrine (E) and norepinephrine (NE) at exhaustion (p less than 0.05). Single ingestion of caffeine accelerated the elimination of E and NE and increased the maximal blood lactic acid. These data suggest that both single and continuous administration of caffeine do not enhance performance during maximal cycle ergometer exercise, but do increase the exercise response of catecholamine. Only a single administration modifies the blood lactate accumulation.     

Effect of Sex,Menstrual Cycle Phase,and Oral Contraceptive Use on Circadian Temperature Rhythms

The circadian rhythm of rectal temperature was continuously recorded over several consecutive days in young men and women on regular nocturnal sleep schedules. There were 50 men, 21 women with natural menstrual cycles [i.e., not taking oral contraceptives (OCs) (10 in the follicular phase and 11 in the luteal phase)], and 14 women using OCs (6 in the pseudofollicular phase and 8 in the pseudoluteal phase). Circadian phase and amplitude were estimated using a curve-fitting procedure, and temperature levels were determined from the raw data. A two-way analysis of variance (ANOVA) on the data from the four groups of women, with factors menstrual cycle phase (follicular, luteal) and OC use (yes, no), showed that temperature during sleep was lower during the follicular phase than during the luteal phase. Since waking temperatures were similar in the two phases, the circadian amplitude was also larger during the follicular phase. The lower follicular phase sleep temperature also resulted in a lower 24-h temperature during the follicular phase. The two-way ANOVA showed that temperature during sleep and 24-h temperature were lower in naturally cycling women than in women taking OCs. A one-way ANOVA on the temperature rhythm parameters from the five groups of subjects showed that the temperature rhythms of the men and of the naturally cycling women in the follicular phase were not significantly different. Both of these groups had lower temperatures during sleep, lower 24-h temperatures, and larger circadian amplitudes than the other groups. There were no significant differences in circadian phase among the five groups studied. In conclusion, menstrual cycle phase, OC use, and sex affect the amplitude and level, but not the phase, of the overt circadian temperature rhythm.     

Effects of Gender and Phase of the Menstrual Cycle on the Kinetics of Ranitidine in Healthy Volunteers

The present study was undertaken to determine if differences exist in the pharmacokinetic parameters of oral ranitidine caused by gender and stage of the menstrual cycle. The study was performed in two steps, in the first a pharmacokinetic study was performed on 10 men (average age 35.5 yrs) and 10 women (average age 34.7 yrs) during the follicular phase, and in the second the pharmacokinetic study was performed only on the same women in their luteal phase. Subjects received a tablet dose of 300 mg ranitidine, and blood samples were drawn at several times after its ingestion. Plasma ranitidine concentration was determined by high performance liquid chromatography. Comparison of the pharmacokinetic parameters of women and men revealed statistically significant differences both in distribution volume (Vd) with values of 2.0 and 6.3 l/kg, Area Under Curve (AUC) with values of 7312.15 and 11471.94 ng/ml/h, and clearance (CLt) with values of 0.65 and 0.59 l/kg/h, respectively. Several pharmacokinetic parameters in women were different in the follicular compared to the luteal phase; for example, Vd was 2.0 and 5.6 l/kg, AUC was 7312.15 and 5195.83 ng/ml/h, and CLt was 0.65 and 0.97 l/kg/h, in the respective phases. Moreover, the maximum concentration (Cmax) was 1086 ng/ml in the follicular vs. 864 ng/ml in the luteal phase. The first study detected differences between men and women in several pharmacokinetic parameters, mainly those indicative of drug availability, for example, Vd, AUC, and CLt. Comparison of data obtained in the follicular phase with those obtained in the luteal phase revealed differences in most pharmacokinetic parameters, which is seemingly indicative of the characteristic physiological changes associated with the luteal phase that largely affect the kinetics and availability of drugs such as ranitidine. Although it has been postulated that hormonal fluctuation within the menstrual cycle phase is the primary cause of documented gender differences in the pharmacokinetics and pharmacodynamics of drugs, further study of related factors is required to fully understand how gender and menstrual cycle rhythms affect the pharmacokinetic process in their entirety.     

Effect of Sex, Menstrual Cycle Phase, and Oral Contraceptive Use on Circadian Temperature Rhythms

The circadian rhythm of rectal temperature was continuously recorded over several consecutive days in young men and women on regular nocturnal sleep schedules. There were 50 men, 21 women with natural menstrual cycles [i.e., not taking oral contraceptives (OCs) (10 in the follicular phase and 11 in the luteal phase)], and 14 women using OCs (6 in the pseudofollicular phase and 8 in the pseudoluteal phase). Circadian phase and amplitude were estimated using a curve-fitting procedure, and temperature levels were determined from the raw data. A two-way analysis of variance (ANOVA) on the data from the four groups of women, with factors menstrual cycle phase (follicular, luteal) and OC use (yes, no), showed that temperature during sleep was lower during the follicular phase than during the luteal phase. Since waking temperatures were similar in the two phases, the circadian amplitude was also larger during the follicular phase. The lower follicular phase sleep temperature also resulted in a lower 24-h temperature during the follicular phase. The two-way ANOVA showed that temperature during sleep and 24-h temperature were lower in naturally cycling women than in women taking OCs. A one-way ANOVA on the temperature rhythm parameters from the five groups of subjects showed that the temperature rhythms of the men and of the naturally cycling women in the follicular phase were not significantly different. Both of these groups had lower temperatures during sleep, lower 24-h temperatures, and larger circadian amplitudes than the other groups. There were no significant differences in circadian phase among the five groups studied. In conclusion, menstrual cycle phase, OC use, and sex affect the amplitude and level, but not the phase, of the overt circadian temperature rhythm.     

No effect of menstrual cycle on myofibrillar and connective tissue protein synthesis in contracting skeletal muscle

We tested the hypothesis that acute exercise would stimulate synthesis of myofibrillar protein and intramuscular collagen in women and that the phase of the menstrual cycle at which the exercise took place would influence the extent of the change. Fifteen young, healthy female subjects were studied in the follicular (FP, n=8) or the luteal phase (LP, n=7, n=1 out of phase) 24 h after an acute bout of one-legged exercise (60 min of kicking at 67% W(max)), samples being taken from the vastus lateralis in both the exercised and resting legs. Rates of synthesis of myofibrillar and muscle collagen proteins were measured by incorporation of [(13)C]leucine. Myofibrillar protein synthesis (means+/-SD; rest FP: 0.053+/-0.009%/h, LP: 0.055+/-0.013%/h) was increased at 24-h postexercise (FP: 0.131+/-0.018%/h, P<0.05, LP: 0.134+/-0.018%/h, P< 0.05) with no differences between phases. Similarly, muscle collagen synthesis (rest FP: 0.024+/- 0.017%/h, LP: 0.021+/- 0.006%/h) was elevated at 24-h postexercise (FP: 0.073+/- 0.016%/h, P<0.05, LP: 0.072+/- 0.015%/h, P<0.05), but the responses did not differ between menstrual phases. Therefore, there is no effect of menstrual cycle phase, at rest or in response to an acute bout of exercise, on myofibrillar protein synthesis and muscle collagen synthesis in women.     

The effect of prior exercise and caffeine ingestion on metabolic rate and hormones in young adult males

The purposes of this study were to examine (a) the effects of acute exercise on metabolic rate 24 and 48 h postexercise and (b) the interaction of acute exercise and the thermic effect of caffeine on metabolic rate and hormonal changes during the late postexercise recovery period. In six young males, who were regular consumers of caffeine, resting energy expenditure was measured before and after caffeine (5 mg.kg-1) and placebo ingestion under the following conditions: (i) control (e.g., no prior exercise), (ii) 24 h postexercise, and (iii) 48 h postexercise. Blood samples were drawn for plasma glucose, insulin, glycerol, free fatty acids, catecholamines, and thyroid hormones (triiodothyronine, thyroxine, and free thyroxine). Results showed that acute exercise did not exert a detectable effect on resting metabolic rate in the late postexercise recovery period, that is, resting metabolic rate was similar among the conditions of control (1.17 +/- 0.12 kcal.min-1), 24 h postexercise (1.16 +/- 0.12), and 48 h postexercise (1.16 +/- 0.11). Caffeine ingestion increased metabolic rate (approximately 7%), but the thermic effect was not different among the experimental conditions. Plasma insulin and norepinephrine were lower after caffeine ingestion, whereas an increase in plasma free fatty acids was noted. Other hormones and substrates did not change significantly in response to caffeine ingestion. Furthermore, the hormonal and substrate milieu was not significantly different 24 and 48 h postexercise when compared with the control condition. Our results support the view that acute exercise does not alter the resting metabolic rate in the late postexercise recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)     

The physiological effects of caffeine in women during treadmill walking

Although the effects of caffeine ingestion on athletic performance in men have been studied extensively, there is limited previous research examining caffeine's effects on women of average fitness levels participating in common modes of physical activity. The purpose of this study was to determine the effect of 2 levels of caffeine dosage on the metabolic and cardiorespiratory responses to treadmill walking in women. Subjects were 20 women (19-28 years of age) of average fitness, not habituated to caffeine. Each subject was assigned randomly a 3-mg x kg(-1) dose of caffeine, 6-mg x kg(-1) dose of caffeine, and placebo for 3 trials of moderate steady-state treadmill walking at 94 m x min(-1) (3.5 mph). Steady-state rating of perceived exertion (RPE), heart rate (HR), respiratory exchange ratio (RER), weight-relative VO2, %VO2max reserve (%VO2R), and rate of energy expenditure (REE) were measured during each trial. Repeated measures analysis of variance revealed that a 6-mg x kg(-1), but not a 3-mg x kg(-1) dose of caffeine increased VO2 (p = 0.04), REE (p = 0.03), and %VO2R (p = 0.03), when compared to the placebo. Caffeine had no effect on RPE, HR, or RER. No significant differences were observed between the placebo trials and the 3-mg x kg(-1) dose trials. Although a 6-mg x kg(-1) dose of caffeine significantly increased REE during exercise, the observed increase (approximately 0.23 kcal x min(-1)) would not noticeably affect weight loss. Because caffeine had no effect on RPE, it would not be prudent for a trainer to recommend caffeine in order to increase a woman's energy expenditure or to decrease perception of effort during mild exercise. These data also demonstrate that caffeine intake should not interfere with monitoring walking intensity by tracking exercise heart rate in women.     

Luteal and follicular glucose fluxes during rest and exercise in 3-h postabsorptive women.

We examined the effects of exercise intensity and menstrual cycle phase on glucose flux rates during rest and exercise in rested and fed (3-h postabsorptive) women. Eight moderately active, eumenorrheic women were studied under conditions of rest (90 min) and exercise (60 min, leg ergometer cycling at 45 and 65% peak oxygen consumption) during follicular and luteal phases. In both menstrual phases, an effect of exercise intensity was evident with glucose rates of appearance and disappearance and metabolic clearance rates: rest < 45% intensity < 65% intensity (P < 0.05). In addition, we observed no significant effect of menstrual phase on glucose rates of appearance and disappearance and metabolic clearance rate during rest or exercise at either intensity. These results are interpreted to mean that in women fed several hours before study 1) glucose flux is directly related to exercise intensity, 2) menstrual cycle phase does not alter glucose flux during rest and exercise, and 3) the subtle effects of endogenous ovarian hormones on glucose kinetics are subordinate to the much larger effects of exercise and recent carbohydrate nutrition.     

Resting and exercise ventilatory chemosensitivity across the menstrual cycle

We hypothesized that resting and exercise ventilatory chemosensitivity would be augmented in women when estrogen and progesterone levels are highest during the luteal phase of the menstrual cycle. Healthy, young females (n = 10; age = 23 ± 5 yrs) were assessed across one complete cycle: during early follicular (EF), late follicular (LF), early luteal, and mid-luteal (ML) phases. We measured urinary conjugates of estrogen and progesterone daily. To compare values of ventilatory chemosensitivity and day-to-day variability of measures between sexes, males (n = 10; age = 26 ± 7 yrs) were assessed on 5 nonconsecutive days during a 1-mo period. Resting ventilation was measured and hypoxic chemosensitivity assessed using an isocapnic hypoxic ventilatory response (iHVR) test. The hypercapnic ventilatory response was assessed using the Read rebreathing protocol and modified rebreathing tests. Participants completed submaximal cycle exercise in normoxia and hypoxia. We observed a significant effect of menstrual-cycle phase on resting minute ventilation, which was elevated in the ML phase relative to the EF and LF phases. Compared with males, resting end-tidal CO(2) was reduced in females during the EF and ML phases but not in the LF phase. We found that iHVR was unaffected by menstrual-cycle phase and was not different between males and females. The sensitivity to chemical stimuli was unaffected by menstrual-cycle phase, meaning that any hormone-mediated effect is of insufficient magnitude to exceed the inherent variation in these chemosensitivity measures. The ventilatory recruitment threshold for CO(2) was generally lower in women, which is suggestive of a hormonally related lowering of the ventilatory recruitment threshold. We detected no effect of menstrual-cycle phase on submaximal exercise ventilation and found that the ventilatory response to normoxic and hypoxic exercise was quantitatively similar between males and females. This suggests that feed-forward and feed-back influences during exercise over-ride the effects of naturally occurring changes in sex hormones.     

Glucose kinetics and exercise performance during phases of the menstrual cycle: effect of glucose ingestion

To study the effect of menstrual cycle phase and carbohydrate ingestion on glucose kinetics and exercise performance, eight healthy, moderately trained, eumenorrheic women cycled at 70% of peak O(2) consumption for 2 h and then performed a 4 kJ/kg body wt time trial. A control (C) and a glucose ingestion (G) trial were completed during the follicular (F) and luteal (L) phases of the menstrual cycle. Plasma substrate concentrations were similar before the commencement of exercise. Glucose rates of appearance and disappearance were higher (P < 0.05) during the 2nd h of exercise in FC than in LC. The percent contribution of carbohydrate to total energy expenditure was greater in FC than in LC, and subjects performed better (13%, P < 0.05) in FC. Performance improved (19% and 26% in FG and LG compared with FC and LC, respectively, P < 0.05) with the ingestion of glucose throughout exercise. These data demonstrate that substrate metabolism and exercise performance are influenced by the menstrual cycle phase, but ingestion of glucose minimizes these effects.     

Low doses of melatonin and diurnal effects on thermoregulation and tolerance to uncompensable heat stress.

This study examined whether the reported hypothermic effect of melatonin ingestion increased tolerance to exercise at 40 degrees C, for trials conducted either in the morning or afternoon, while subjects were wearing protective clothing. Nine men performed four randomly ordered trials; two each in the morning (0930) and afternoon (1330) after the double-blind ingestion of either two placebo capsules or two 1-mg capsules of melatonin. Despite significant elevations in plasma melatonin to over 1,000 ng/ml 1 h after the ingestion of the first 1-mg dose, rectal temperature (T(re)) was unchanged before or during the heat-stress exposure. Also, all other indexes of temperature regulation and the heart rate response during the uncompensable heat stress were unaffected by the ingestion of melatonin. Initial T(re) was increased during the afternoon (37.1 +/- 0.2 degrees C), compared with the morning (36.8 +/- 0.2 degrees C) exposures, and these differences remained throughout the uncompensable heat stress, such that final T(re) was also increased for the afternoon (39.2 +/- 0.2 degrees C) vs. the morning (39.0 +/- 0.3 degrees C) trials. Tolerance times and heat storage were not different among the exposures at approximately 110 min and 16 kJ/kg, respectively. It was concluded that this low dose of melatonin had no impact on tolerance to uncompensable heat stress and that trials conducted in the early afternoon were associated with an increased T(re) tolerated at exhaustion that offset the circadian influence on resting T(re) and thus maintained tolerance times similar to those of trials conducted in the morning.     

Effects of gender and phase of the menstrual cycle on the kinetics of ranitidine in healthy volunteers

The present study was undertaken to determine if differences exist in the pharmacokinetic parameters of oral ranitidine caused by gender and stage of the menstrual cycle. The study was performed in two steps, in the first a pharmacokinetic study was performed on 10 men (average age 35.5 yrs) and 10 women (average age 34.7 yrs) during the follicular phase, and in the second the pharmacokinetic study was performed only on the same women in their luteal phase. Subjects received a tablet dose of 300 mg ranitidine, and blood samples were drawn at several times after its ingestion. Plasma ranitidine concentration was determined by high performance liquid chromatography. Comparison of the pharmacokinetic parameters of women and men revealed statistically significant differences both in distribution volume (Vd) with values of 2.0 and 6.3 l/kg, Area Under Curve (AUC) with values of 7312.15 and 11471.94 ng/ml/h, and clearance (CLt) with values of 0.65 and 0.59 l/kg/h, respectively. Several pharmacokinetic parameters in women were different in the follicular compared to the luteal phase; for example, Vd was 2.0 and 5.6 l/kg, AUC was 7312.15 and 5195.83 ng/ml/h, and CLt was 0.65 and 0.97 l/kg/h, in the respective phases. Moreover, the maximum concentration (Cmax) was 1086 ng/ml in the follicular vs. 864 ng/ml in the luteal phase. The first study detected differences between men and women in several pharmacokinetic parameters, mainly those indicative of drug availability, for example, Vd, AUC, and CLt. Comparison of data obtained in the follicular phase with those obtained in the luteal phase revealed differences in most pharmacokinetic parameters, which is seemingly indicative of the characteristic physiological changes associated with the luteal phase that largely affect the kinetics and availability of drugs such as ranitidine. Although it has been postulated that hormonal fluctuation within the menstrual cycle phase is the primary cause of documented gender differences in the pharmacokinetics and pharmacodynamics of drugs, further study of related factors is required to fully understand how gender and menstrual cycle rhythms affect the pharmacokinetic process in their entirety.     

Physiological variability of fluid-regulation hormones in young women.

We tested the physiological reliability of plasma renin activity (PRA) and plasma concentrations of arginine vasopressin (P[AVP]), aldosterone (P[ALD]), and atrial natriuretic peptide (P[ANP]) in the early follicular phase and midluteal phases over the course of two menstrual cycles (n = 9 women, ages 25 +/- 1 yr). The reliability (Cronbach's alpha >/=0.80) of these hormones within a given phase of the cycle was tested 1) at rest, 2) after 2.5 h of dehydrating exercise, and 3) during a rehydration period. The mean hormone concentrations were similar within both the early follicular and midluteal phase tests; and the mean concentrations of P[ALD] and PRA for the three test conditions were significantly greater during the midluteal compared with the early follicular phase. Although Cronbach's alpha for resting and recovery P[ANP] were high (0.80 and 0.87, respectively), the resting and rehydration values for P[AVP], P[ALD], and PRA were variable between trials for the follicular (alpha from 0.49 to 0.55) and the luteal phase (alpha from 0.25 to 0. 66). Physiological reliability was better after dehydration for P[AVP] and PRA but remained low for P[ALD]. Although resting and recovery P[AVP], P[ALD], and PRA were not consistent within a given menstrual phase, the differences in the concentrations of these hormones between the different menstrual phases far exceeded the variability within the phases, indicating that the low within-phase reliability does not prevent the detection of menstrual phase-related differences in these hormonal variables.     

Impact of stress, gender and menstrual cycle on immune system: possible role of nitric oxide

Stress is a factor found to be involved in the etiology of many diseases. Gender and menstrual cycle phases are other factors affecting the predisposition of individuals for certain diseases. Results from animal and human studies suggest that the distribution of immune system cells may change at different phases of the menstrual cycle. Acute mental stress in humans alters immune variables, too. The increase in the number of natural killer (NK) cells is the most consistent finding among the immune variables, though there are controversies for the other lymphocyte groups. Nitric oxide (NO) as an immune mediator has an unsettled role whether it causes the redistribution of the immune cells, or is an end product of lymphocyte activation. This study was planned to investigate the effect of mental stress on lymphocyte subtypes and the role of NO, for men and women at different phases of the cycle. For this purpose, healthy men (n = 10) and women (n = 10), during the follicular and luteal phases underwent Stroop colour-word interference and cold pressor tests. The immune system responses before and after the tests were determined by cell counts with the flowcytometer. Menstrual cycle phase was ascertained by plasma estrogen and progesterone measurements. Stress response was evaluated by blood pressure (BP) and heart rate (HR) measurements throughout the tests and plasma cortisol and urinary metanephrine and vanillylmandelic acid (VMA) measurements before and after the tests. Plasma and urinary NO determinations were performed before and after the test was completed. All the results were analysed with the appropriate statistical methods. The luteal phase differed from the other groups due to the presence of suppressed immune response to acute stress, including decreased CD4/CD8 ratio and NK cell percentage. On the other hand, acute stress caused a shift from cellular to humoral immunity in men. As indicated by these results, individual reaction towards stress is affected by gender and menstrual cycle phase. NO appears to be a possible effector molecule for these differences.     

Effects of caffeine on blood pressure, heart rate, and forearm blood flow during dynamic leg exercise

This study examined the acute effects of caffeine on thecardiovascular system during dynamic leg exercise. Ten trained,caffeine-naive cyclists (7 women and 3 men) were studied at rest andduring bicycle ergometry before and after the ingestion of 6 mg/kgcaffeine or 6 mg/kg fructose (placebo) with 250 ml of water. Afterconsumption of caffeine or placebo, subjects either rested for 100 min(rest protocol) or rested for 45 min followed by 55 min of cycleergometry at 65% of maximal oxygen consumption (exercise protocol).Measurement of mean arterial pressure (MAP), forearm blood flow (FBF),heart rate, skin temperature, and rectal temperature and calculation offorearm vascular conductance (FVC) were made at baseline and at 20-minintervals. Plasma ANG II was measured at baseline and at 60 minpostingestion in the two exercise protocols. Before exercise, caffeineincreased both systolic blood pressure (17%) and MAP (11%) withoutaffecting FBF or FVC. During dynamic exercise, caffeine attenuated theincrease in FBF (53%) and FVC (50%) and accentuated exercise-inducedincreases in ANG II (44%). Systolic blood pressure and MAP were alsohigher during exercise plus caffeine; however, these increases weresecondary to the effects of caffeine on resting bloodpressure. No significant differences were observed inheart rate, skin temperature, or rectal temperature. These findingsindicate that caffeine can alter the cardiovascular response to dynamicexercise in a manner that may modify regional blood flow andconductance.