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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2004-1344
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 6 3312-3317
Copyright © 2005 by The Endocrine Society

Sex Hormone Suppression Reduces Resting Energy Expenditure and ß-Adrenergic Support of Resting Energy Expenditure

Danielle S. Day, Wendolyn S. Gozansky, Rachael E. Van Pelt, Robert S. Schwartz and Wendy M. Kohrt

Division of Geriatric Medicine (D.S.D., W.S.G., R.E.V.P., R.S.S., W.M.K.), University of Colorado Health Sciences Center, Denver, Colorado 80262; and Department of Integrative Physiology (D.S.D., R.S.S., W.M.K.), University of Colorado, Boulder, Colorado 80309

Address all correspondence and requests for reprints to: Wendy Kohrt, Division of Geriatric Medicine, 4200 East Ninth Avenue, B179, Denver, Colorado 80262. E-mail: wendy.kohrt{at}uchsc.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Resting energy expenditure (REE) decreases with aging and may decrease in women as a result of the menopause, potentially contributing to weight gain. REE has been observed to fluctuate during the menstrual cycle, suggesting regulation by sex hormones. The aim of the present study was to determine the effects of suppressing estrogen and progesterone on REE. Fourteen premenopausal women, 29 ± 5 yr old (mean ± SD), were studied in the midluteal menstrual phase (ML) and after 6 d of GnRH antagonist therapy (GnRHant) administered in the follicular menstrual phase. REE was measured by indirect calorimetry in the morning after a 12-h fast and again during ß-adrenergic blockade to determine sympathetic nervous system (SNS) support of REE. Treatment with GnRHant significantly decreased REE (1405 ± 42 vs. 1334 ± 36 kcal/d, mean ± SE, ML vs. GnRHant; P = 0.002). Additionally, SNS blockade tended to alter REE more during ML than during GnRHant (–19 ± 10 vs. 5 ± 11 kcal/d; P = 0.14). Suppression of sex hormones to postmenopausal levels by GnRHant reduced REE in young healthy women. These findings suggest that the withdrawal of estrogen and/or progesterone attenuates REE, possibly through a SNS-mediated mechanism.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
RESTING ENERGY EXPENDITURE (REE) accounts for 60–75% of total daily energy expenditure and decreases with age (1, 2) and physical inactivity (3). It is well known that fat-free mass (FFM) accounts for the majority of inter-individual variability in REE (4). However, other physiological factors, such as sympathetic nervous system (SNS) activity (5, 6) and endocrine status (e.g. thyroid hormone) (7), also contribute to observed population differences in REE. Even small reductions in REE increase risk for weight gain and subsequent obesity-related diseases (8). Therefore, it is important to consider mechanisms other than alterations in FFM that may modulate REE.

Some studies of premenopausal women (9, 10, 11, 12, 13), but not all (14, 15), have found that REE is higher during the midluteal phase (ML) of the menstrual cycle, when estrogens (E) [including both estrone (E1) and estradiol (E2)] and progesterone (P4) are elevated, compared with the early follicular phase (EF), when both hormones are low, suggesting a role for sex hormones in the regulation of REE. The discordance among studies may be due, in part, to daily fluctuations in hormone concentrations combined with a lack of adequate control over the timing of the REE measurements with respect to menstrual cycle phase.

To our knowledge, the effects on REE of reducing endogenous E and P4 in a controlled manner have not been determined. Thus, one aim of the present study was to determine whether suppression of endogenous E and P4 for 6 d using a GnRH antagonist caused a reduction in REE when compared with the high-hormone, ML phase.

One mechanism by which E and/or P4 may modulate REE is through the ß-adrenergic arm of the SNS, which has been shown to contribute to resting metabolism (5, 6, 16, 17, 18). In premenopausal women, muscle sympathetic nerve activity, an indirect measure of tonic SNS activity, is higher in the ML than the EF phase (19). However, we are not aware of any studies that have determined whether menstrual cycle fluctuations in SNS activity and REE are linked. In this context, a second aim of the present study was to determine whether sex hormone status influences SNS support of REE.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Fifteen healthy premenopausal women, aged 29 ± 5 yr (mean ± SD), participated in the study, which was approved by the Colorado Multiple Institution Review Board. All subjects were eumenorrheic (cycle length, 25–31 d), nonsmokers, and not taking oral contraceptives or any medications known to affect REE. Screening procedures to determine eligibility for the study included a medical history, physical examination, blood chemistries, and a graded treadmill exercise stress test. Inclusion criteria for participation were as follows: resting heart rate of at least 50 beats/min, normal serum TSH value, normal treadmill stress test, and body mass index of 30 kg/m2 or less. The nature, purpose, and risks of the study were explained to each subject, and all subjects provided written informed consent before participation.

Testing timeline

Menstrual cycle phases were determined over at least 2 months by menstrual calendars and urine ovulation prediction kits (ClearPlan Easy; Unipath Diagnostics, Waltham, MA). REE was measured during the EF (2–6 d after onset of menses) and ML (7–9 d after positive ovulation test) phases of the menstrual cycle and after 6 d GnRH antagonist therapy (GnRHant) (Cetrotide; Serono Inc., Rockland, MA). On the ML and GnRHant testing days, REE was measured a second time during complete ß-adrenergic blockade to determine SNS support of REE.

GnRH antagonist therapy

A 3-mg dose of GnRHant was administered on the first day (during the follicular phase of the menstrual cycle), followed by daily self-administered injections of 0.25 mg. This regimen has been shown to suppress serum E and P4 concentrations to postmenopausal levels (20, 21).

Procedures

Subjects were admitted to the University of Colorado Health Sciences Center General Clinical Research Center (GCRC) the evening before each test. They consumed a standardized meal between 1800 and 1900 h and then consumed nothing except water until the end of the experiment the following morning. Additionally, subjects were instructed to abstain from strenuous physical activity for 24 h before each experiment. To confirm consistent diet and physical activity behavior, subjects kept diet records and wore pedometers for 3 d before each test.

Subjects were awakened in the GCRC at 0500 h on the morning of the procedure for voiding and placement of physiological monitoring instruments (electrocardiogram and blood pressure) and the iv catheter for subsequent blood draws and infusion of propranolol. Subjects then returned to rest or sleep until the start of the first REE measurement between 0600 and 0630 h. Metabolic data were collected for 35 min using the ventilated hood indirect calorimetry technique (Delta Trac Metabolic Unit; SensorMedics, Yorba Linda, CA). The final 30 min of data were averaged, and REE was calculated using the Weir formula. Day-to-day variability of REE measured in four young women on three mornings within a 4-d time period was 2.9 ± 1.2% [mean coefficient of variation (CV)]. On the ML and GnRHant days, measurement of REE was repeated after complete ß-adrenergic blockade (0.2 mg/kg bolus of propranolol, followed by a 0.004 mg/kg·min–1 continuous drip) to determine SNS support of RMR, as described previously (5).

Blood samples were obtained immediately after the first measurement of REE and later analyzed for norepinephrine (NE), epinephrine (Epi), E1, E2, SHBG, P4, testosterone, LH, FSH, and thyroid-stimulating hormones (T3, T4, and T3 resin uptake).

Hormone assays. All hormone assays were performed in the Core Laboratory of the GCRC. Catecholamines were analyzed by HPLC (Dionex, Sunnyvale, CA). The respective intra- and interassay CVs were 4.5 and 4.1% for NE and 5.4 and 5.2% for Epi. The sensitivity was 20 pg/ml for both Epi and NE. E1, E2, LH, and FSH were determined by RIA (Diagnostic Systems Laboratories, Webster, TX). Respective intra- and interassay CVs and sensitivities were 8.7%, 8.6%, and 0.3 pg/ml for E1 and 6%, 11%, and 8 pg/ml for E2. Interassay CVs for FSH and LH were 9.1 and 14.6%, respectively, and the sensitivity for both assays was 0.2 mIU/ml; intraassay CVs were not available. T3 (Nichols Institute Diagnostics, San Clemente, CA), free T4, and total testosterone (Beckman Coulter, Inc., Fullerton, CA) were analyzed by chemiluminescence immunoassay. The free testosterone index was calculated using the measured SHBG concentrations and an assumed albumin concentration of 43 g/liter (22). SHBG was analyzed by immunoradiometric assay (Diagnostic Systems Laboratories). Intra- and interassay CVs were 5.1 and 12%, respectively, and sensitivity was 10 nmol/liter.

Diet and physical activity records. Three-day diet records were reviewed and analyzed by GCRC bionutritionists using Nutrition IV software (version 2.2; First DataBank, Inc., San Bruno, CA). Energy intake over the 3-d recording period was averaged for each testing phase. Subjects also wore pedometers (Eagle 120; Accusplit, San Jose, CA) for 3 d before each testing phase, and the average number of step counts was calculated for each phase.

Body composition. Total body mass, fat mass, and FFM were determined by dual-energy x-ray absorptiometry (Delphi-W version 11.2; Hologic Inc., Bedford, MA). This measure was performed at the beginning of the study, and the data were used only to describe the subject population.

Statistical analyses. A one-way repeated-measures ANOVA was used to test for significant changes in the primary outcome, REE, and other variables measured in the EF and ML menstrual cycle phases and after GnRHant (version 8.0; SAS Institute, Inc., Cary, NC). In the event of a significant main effect of cycle phase or treatment, Tukey post hoc tests were used to determine which means were significantly different. SNS support of REE was calculated as the difference between REE measured in the basal state and during ß-adrenergic blockade. The extent of decrease in REE in response to ß-adrenergic blockade was assumed to reflect SNS support of REE in the basal state. A paired t test was used to determine whether SNS support of REE was significantly reduced after sex hormone suppression with GnRHant compared with the high-hormone period of the ML phase of the menstrual cycle. Because it appeared that some women did not respond to ß blockade with a decrease in REE at baseline, data were analyzed in two separate ways: first, including only responders in the analysis, and, second, using an analysis of covariance in all subjects (responders and nonresponders) to determine whether the change in REE from ML to GnRHant was related to SNS support of REE at baseline (ML). Statistical significance was defined as P ≤ 0.05. All data are reported as mean ± SE unless otherwise specified.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
One participant demonstrated exceptionally high estradiol levels during EF (103 pg/ml), and her levels remained elevated after treatment with GnRHant (233 pg/ml). Because the specific aim of the study was to determine the effects of menopausal-like reductions in sex hormones on REE, we chose to exclude this subject from analysis. Therefore, all data presented are for a total of 14 participants.

Subject characteristics

At study entry, body mass index of the participants was 24.0 ± 2.7 kg/m2, and relative body fat was 28.5 ± 4.1% of body weight (mean ± SD). Body mass, energy intake, and physical activity (steps per day) for each testing phase are presented in Table 1Go. There were no differences in body mass or energy intake among the EF, ML, and GnRHant conditions. Physical activity (steps per day) was significantly higher in the EF phase compared with both ML and GnRHant.


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  		TABLE 1. Body mass, energy intake, and physical activity at each testing phase

 
Sex hormones and REE

REE was higher in the ML phase than in the EF phase (Fig. 1Go) (1405 ± 42 vs. 1376 ± 43 kcal/d; 5878 ± 176 vs. 5757 ± 180 kJ/d; P = 0.05). There were no differences in respiratory exchange ratio (RER) (ML, 0.85 ± 0.01; EF, 0.86 ± 0.01), although oxygen uptake (VO2) was slightly but significantly elevated in ML compared with EF (204 ± 6 vs. 198 ± 7 ml/min; P = 0.04), with no differences in carbon dioxide production (VCO2) (174 ± 6 vs. 173 ± 7 ml/min). Serum E2 and P4 concentrations confirmed correct timing of menstrual phases (Table 2Go).



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  		FIG. 1. REE in the EF and ML phases and after GnRHant. REE was significantly higher during the ML phase than during the EF or GnRHant phases and higher during the EF than the GnRHant phase. SI unit conversion: REE (kcal) x 4.184 = kJ.

 

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  		TABLE 2. Serum sex and metabolic hormones at each testing phase

 
After 6 d of GnRHant treatment, serum estrogens (E1 and E2) and P4 were significantly reduced by 56 ± 3.9, 57 ± 3.5, and 87 ± 3.9%, respectively, compared with the ML phase, confirming medication compliance (Table 2Go). E1 and E2 were also significantly lower during GnRHant when compared with the EF phase. Both FSH and LH were significantly lower during GnRHant when compared with the EF phase, but only FSH was reduced when compared with the ML phase. The free testosterone index was higher and SHBG was lower during the EF phase when compared with ML phase, but values measured during GnRHant were not different from either menstrual phase.

REE was significantly reduced in response to GnRHant treatment compared with ML (Fig. 1Go) (1334 ± 36 vs. 1405 ± 42 kcal/d; 5581 ± 151 vs. 5878 ± 176 kJ/d; P = 0.002). REE during the GnRHant phase was also significantly reduced when compared with the EF phase (P = 0.04). RER values for ML and GnRHant were not significantly different (0.85 ± 0.01 and 0.86 ± 0.01), but both VO2 and VCO2 were significantly higher in ML compared with GnRHant (VO2, 204 ± 6 vs. 194 ± 5 ml/min, P = 0.002; VCO2, 174 ± 6 vs. 167 ± 5 ml/min, P = 0.02). Neither RER, VO2, nor VCO2 values were significantly different between EF and GnRHant conditions (RER, 0.86 ± 0.01 vs. 0.86 ± 0.01; VO2, 199 ± 7 vs. 194 ± 5 ml/min; VCO2, 173 ± 7 vs. 167 ± 5 ml/min, respectively).

ß-Adrenergic support of REE

The magnitude of reduction in REE during ß-adrenergic blockade tended to be less in the GnRHant phase compared with the ML phase (Fig. 2Go) (5 ± 11 vs. –19 ± 10 kcal/d; 21 ± 46 vs. –79 ± 42 kJ/d; P = 0.14). A subset of subjects (n = 6) from this cohort was identified as nonresponders to the administration of propranolol, due to the fact that no reduction in REE was observed in these individuals in response to ß-adrenergic blockade at baseline (ML). The trend for decreased SNS support of REE during GnRHant compared with the ML phase became stronger when only the eight responders were included in the analysis (1 ± 19 vs. –44 ± 8 kcal/d; 4 ± 79 vs. –184 ± 33 kJ/d; P = 0.08). However, including all subjects in an analysis of covariance, SNS support of REE during the ML phase was not a significant determinant of the change in REE from ML to GnRHant (P = 0.39).



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  		FIG. 2. SNS support of REE, measured as the change in REE in response to ß-adrenergic blockade with propranolol. SNS support of REE tended to be reduced after GnRHant compared with the mid- luteal phase. SI unit conversion: REE (kcal) x 4.184 = kJ.

 
Metabolic hormones

There were no significant differences in T3, NE, or Epi among the testing phases. However, free T4 tended to be higher in response to GnRHant treatment compared with the ML phase (P = 0.06) (Table 2Go).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
New findings

This is the first study to show that REE is reduced in response to pharmacological suppression of sex hormones in premenopausal women. If this experimental paradigm mimics the effects of natural sex hormone withdrawal during menopause, it would suggest that the propensity for weight gain in women after the menopause may be a result of decreased REE. Furthermore, we found that SNS support of REE tended to be greater in the ML phase, when E and P4 are elevated, than during suppression of E and P4 by GnRHant, suggesting that sex hormones may influence REE via a SNS-mediated mechanism.

The results of the present study corroborate the findings of previous studies showing higher REE in the ML phase of the menstrual cycle, when E and P4 are elevated, compared with the EF phase, when E and P4 are both low (9, 10, 11, 12, 13). The failure to find significant fluctuations in REE across the menstrual cycle in some studies (14, 15, 23) may have been due to inadequate control for hormonal phases, dietary intake, or physical activity. In the present study, menstrual cycle phases were established using ovulation prediction kits and confirmed with serum hormone analyses at each phase of testing. Additionally, subjects were asked not to perform vigorous physical activity for 24 h before testing, and all subjects stayed on the GCRC inpatient unit and ate standardized meals the night before each test for additional control of intra-individual variability in diet and physical activity.

The novel finding from this study was that REE was significantly reduced, compared with the ML phase, when E and P4 were pharmacologically suppressed, providing additional evidence for a positive association of sex hormones with REE. There have been no longitudinal studies of REE in women across the menopausal transition to lend insight into how the natural withdrawal of sex hormones influences REE. However, there is evidence from several randomized controlled trials that weight gain is attenuated in postmenopausal women on hormone therapy (HT) compared with those on placebo treatment (24, 25, 26, 27, 28). The results from our study suggest that stimulation of REE by E and/or P4 may contribute to the protection against weight gain that has been observed in response to HT.

The generalizability of our study results to postmenopausal women has limitations. Sex hormone suppression by a GnRH antagonist does not mimic all effects of the menopause. Indeed, one difference between the pharmacological suppression of E and P4 and natural menopause is the effect on LH and FSH. Postmenopausal women have elevated FSH and LH levels compared with premenopausal women. However, in the current model, FSH was lower in the GnRHant phase than in the EF and ML phases. LH tended to be lower during GnRHant therapy than in the ML phase and was significantly lower than in the EF phase. Therefore, it is unclear whether the reduction in REE observed in response to GnRHant was related to reductions in E, P4, LH, or a combination thereof. To our knowledge, the independent effects of LH and FSH on REE have not been studied.

ß-Adrenergic support of REE

Previous studies have demonstrated support of REE by the ß-adrenergic arm of the SNS, such that complete ß-adrenergic blockade elicits a reduction in REE in young and old women and men (5, 6, 17). SNS support of REE is lower in women compared with men and lower in older compared with young individuals (16). It is not known whether SNS support of REE is also lower in postmenopausal vs. premenopausal women. In the present study, ß-adrenergic support of REE tended to be lower after suppression of sex hormones compared with the ML phase of the menstrual cycle, but there was a high degree of variability in this response. There is evidence for inter-individual variability with respect to hemodynamic responses to ß-adrenergic blockade associated with ß-adrenergic receptor polymorphisms (29). It is not known whether such polymorphisms could also influence the REE response to ß blockade. We identified six individuals in our cohort who did not demonstrate a reduction in REE in response to propranolol administration during the ML phase assessment. However, baseline (ML) SNS support of REE did not explain the change in REE from ML to GnRHant. Importantly, the mean change in REE from ML to GnRHant was similar for both responders and nonresponders, suggesting that SNS support of REE is only one potential mechanism mediating the reduction in REE with sex hormone suppression.

Alternative mechanisms

It is important to consider other potential mechanisms for the reduction in REE in response to GnRHant therapy. Age-related declines in FFM explain the majority of the observed age-related decrease in REE in women (30). Although several months of sex hormone suppression using GnRH agonist therapy causes a reduction in FFM (31), the short duration of treatment with the antagonist in this study (6 d) minimized the likelihood of changes in body composition. Results from the present study demonstrated that reducing sex hormones to postmenopausal levels lowered REE over a short period of time of weight stability, during which minimal changes in body composition would be expected to occur.

Lower levels of physical activity in a sex hormone-deficient state could explain lower REE. There is evidence from one animal study that ovariectomy results in reduced spontaneous physical activity (32). We obtained a gross measure of overall physical activity using step counts from pedometers worn by the subjects on the 3 d before testing. Step counts during the EF phase were significantly higher than during the ML phase (Table 2Go), discounting the likelihood that the lower REE in the EF phase was related to reduced physical activity. Also, there were no differences in step counts between the ML and GnRHant phases, despite differences in REE.

Thyroid hormones also mediate REE (7). In the present study, T3 hormone levels were similar in EF, ML, and GnRHant phases. Free T4 was higher in the EF compared with ML and tended to be higher still in the GnRHant phase. This pattern is inconsistent with a stimulatory effect of thyroid hormones on REE, because the highest concentrations were observed during the phases with the lowest REE. Therefore, it does not appear that the GnRHant-induced decrease in REE was related to thyroid hormone status.

Testosterone may also influence REE. Suppression of testosterone after 10 wk of GnRH agonist administration was associated with reductions in REE in young men (33). Whether the effect was directly mediated by a reduction in testosterone or the subsequent reduction in the aromatization of testosterone to estrogen could not be elucidated in that study. Furthermore, subjects experienced a significant decrease in FFM, which may have contributed to the observed decline in REE. In the present study, the serum free testosterone index was higher in the EF compared with the ML phase but was not different between the ML and GnRHant phases (Table 2Go). It is unlikely that the higher free testosterone index during the EF phase contributed to the lower REE observed in that phase compared with ML. Also, it appears that factors other than free testosterone index mediated the reduction in REE after GnRHant administration. Future studies should address the independent effects of E, P4, and testosterone on REE and/or SNS support of REE.

Limitations

The purpose of this study was to determine the effects of a pharmacologically induced reduction in sex hormones on REE and SNS support of REE. We chose this model to generate menopause-like reductions in E2 and P4, without confounding body composition and lifestyle changes that accompany menopause and may influence REE. However, this model does not mimic the gonadotropin changes that occur during the menopause. Whether the results of this study would be reproduced in a longitudinal observation of changes in REE across the menopause transition remains to be determined. The duration of GnRHant treatment in the present study was only 6 d, and it is not known whether the reduction in REE would persist with longer suppression of sex hormones. However, the observation that fat mass increased significantly in response to 4–6 months of GnRH agonist therapy (31, 34) suggests that there is a long-term effect of sex hormone suppression on energy balance.

The fact that gonadotropin concentrations were altered with the GnRHant therapy demonstrates the effect of the drug on the pituitary. It is possible that other pituitary hormones may be affected by this intervention and could have contributed to the observed changes in REE or SNS support of REE. In particular, both cortisol and growth hormone are related to sex hormone dynamics (35, 36), and growth hormone stimulates REE (37). Finally, the GnRHant may have had an independent effect on REE/SNS support of REE.

Summary

In conclusion, we have shown that a GnRHant-mediated reduction in E and P4 decreased REE from the ML phase. Previous studies have demonstrated an association between reduced REE and weight gain (8). If the present findings of reduced REE in response to pharmacological suppression of sex hormones in premenopausal women are indicative of what occurs in postmenopausal women, withdrawal of sex hormones at menopause may contribute to decreased REE, thereby increasing propensity for weight gain and risk for obesity-related diseases. Future studies should determine the effects of prolonged sex hormone withdrawal on REE and body composition changes. We have also suggested a potential mechanism by which the reduction in REE after sex hormone suppression may be mediated, illustrated by the trend for a reduction in SNS support of REE after sex hormone suppression. Whether E or P4 is the predominant factor mediating these effects remains to be determined. Exploration of the mechanisms by which sex hormones regulate REE may be useful in the development of alternatives to HT for postmenopausal women. These findings also suggest the need for older women to maintain, or even increase, physical activity after the menopause to counter the potential suppressive effect of reduced sex hormones on REE.


   Acknowledgments
 
We thank the staffs of the University of Colorado Health Sciences Center General Clinical Research Center and Energy Balance Core of the Clinical Nutrition Research Unit for their assistance in conducting this study. Additionally, we thank the research subjects for volunteering their time. Cetrotide was kindly provided by Serono, Inc. (Rockland, MA).


   Footnotes
 
This research was supported by the following: National Institutes of Health (NIH) Grants R01 AG18198 and T32 AG00279 (to D.S.D.), M01 RR00051 (to the General Clinical Research Center), P30 DK48520 (to the Clinical Nutrition Research Unit), K01 AG19630 (to R.E.V.P.), F32 AG05899 (to W.S.G.), a Hartford/Jahnigen Center of Excellence Faculty development award (to W.S.G.), the Glenn/American Federation on Aging Research, a Gatorade Sports Science Institute student grant, and a Woodrow Wilson/Johnson & Johnson dissertation grant in Women’s Health (to D.S.D.).

First Published Online March 1, 2005

Abbreviations: CV, Coefficient of variation; E, estrogen; E1, estrone; E2, estradiol; EF, early follicular phase; Epi, epinephrine; FFM, fat-free mass; GCRC, General Clinical Research Center; GnRHant, GnRH antagonist therapy; HT, hormone therapy; ML, midluteal menstrual phase; NE, norepinephrine; P4, progesterone; REE, resting energy expenditure; RER, respiratory exchange ratio; SNS, sympathetic nervous system; VCO2, carbon dioxide production; VO2, oxygen uptake.

Received July 15, 2004.

Accepted February 22, 2005.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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