Glucose kinetics and exercise performance during phases of the
menstrual cycle: effect of glucose ingestion
S. E.
Campbell,
D. J.
Angus, and
M. A.
Febbraio
Exercise Physiology and Metabolism Laboratory, Department of
Physiology, The University of Melbourne, Parkville, Victoria 3010, Australia
 |
ABSTRACT |
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 O2 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.
estrogen; progesterone; carbohydrate metabolism; endurance exercise
 |
INTRODUCTION |
ALTHOUGH
TRADITIONALLY KNOWN for their role in reproduction, the ovarian
hormones are also thought to exert significant metabolic effects.
Studies in animals have consistently demonstrated that 17
-estradiol
(E2) is a potent promoter of increased lipid oxidation during endurance exercise (18, 22), resulting in a sparing of muscle glycogen (22). This effect has also been seen in
humans (16, 35), although not consistently
(15). In contrast, progesterone is known to reverse many
"estrogenic" effects, including increased fat oxidation
(18). Levels of progesterone are 12-20 times greater during the luteal phase than during the follicular phase, whereas estrogen is only ~3 times greater (24). Hence, varying
levels of these hormones throughout the menstrual cycle could alter
skeletal muscle metabolism during exercise.
Previous studies investigating exercise metabolism in different
phases of the menstrual cycle have produced equivocal results. Several
studies investigating short-term or intermittent exercise have found no
differences between the follicular and the luteal phase (11,
27). Additionally, two studies have found no phase effect on
metabolism during prolonged exercise of
90 min (3, 21).
Conversely, a number of studies have found that menstrual cycle phase
does indeed affect hormonal and metabolic response to exercise
(16, 19, 26, 29), particularly in a carbohydrate (CHO)-depleted nutritional state (4, 25).
This study investigated the metabolic requirements and glucose
kinetics during prolonged exercise in women in the presence and absence
of glucose ingestion. Additionally, we sought to determine whether
glucose ingestion increases exercise performance in a race-type (time
trial) setting and whether metabolism and exercise performance, with
and without glucose supplementation, are influenced by the phase of the
menstrual cycle. We hypothesized that menstrual cycle phase would
affect exercise metabolism, with elevated levels of the ovarian
hormones in the luteal phase decreasing CHO oxidation during exercise.
Furthermore, we hypothesized that because women use more fat and less
CHO than their male counterparts (15, 36), the benefits of
glucose supplementation would not be as marked as previously
demonstrated in men (2, 9). Recently, Bailey et al.
(3) demonstrated that, compared with a placebo, ingestion
of CHO increased time to fatigue in the follicular and luteal phases,
indicating that it is beneficial in some parameters of exercise.
However, the reasons for the onset of fatigue remain elusive and are
likely to include factors other than metabolism, such as neurological
responses to exercise (10). Consequently, fatigue is
perhaps not the best parameter to use when determining the metabolic
effects of the ovarian hormones. Evaluation of the effect of CHO
ingestion on glucose kinetics and exercise performance using a time
trial model will provide new information on glucose metabolism during
prolonged exercise in women.
 |
METHODS |
Subjects.
Eight healthy, nonsmoking, endurance-trained women with a peak
O2 consumption (
O2 peak) of
50 ml · kg
1 · min
1
volunteered as subjects for the study. Subjects were eumenorrheic and
were not taking any oral contraceptives for
6 mo before testing. Each
subject was made fully aware of the procedures and risks associated
with the study, both verbally and in writing. All subjects completed a
medical and a menstrual questionnaire and provided written informed
consent. This experiment was approved by The University of Melbourne
Human Research Ethics Committee.
Preexperimental protocol.
To analyze the menstrual cycle before the commencement of trials,
subjects collected daily urine samples for determination of estrone
glucuronide and pregnanediol glucuronide concentrations, urinary
metabolites of estrogen and progesterone (6). This ensured
appropriate changes in hormone levels between the follicular and luteal
phases of their menstrual cycle and allowed for accurate determination
of each subject's menstrual cycle duration. Additionally, blood
samples taken before the commencement of exercise were analyzed for
E2 and progesterone to further check menstrual phase and status.
During the follicular phase before the first exercise trial, a
O2 peak test was performed on an
electromagnetically braked cycle ergometer (LODE Instrument, Groningen,
The Netherlands). A familiarization trial was also completed during the
menstrual cycle preceding experimental trials to allow subjects to
become comfortable with the laboratory setting and the experimental
protocol. In the 24 h before the
O2 peak test, the familiarization trial, and all experimental trials, subjects were instructed to refrain
from strenuous exercise, alcohol, tobacco, and caffeine. Before the
four experimental trials, subjects were provided with food parcels
(12.6 MJ; 71% CHO, 15% protein, and 14% fat) to be consumed on the
day preceding each trial. No food was permitted on waking on the
morning of an experimental trial. Subjects were instructed to strictly
adhere to the diet and were permitted to consume only water ad libitum.
These pretrial exercise and lifestyle controls helped ensure that
hormonal and metabolite values were stable and similar for each subject
before each experimental trial.
Experimental trials.
Four experiments were conducted over the course of at least two
menstrual cycles, with each test occurring at a specific time during
the menstrual cycle, previously determined for each subject by
urinalysis. The menstrual phases were confirmed by urinalysis on the
morning of each experimental trial. To avoid confounding phase effect
with test order, subjects were randomly allocated to different test
orders, with four subjects commencing in the follicular phase and four
in the luteal phase.
On arrival at the laboratory for the experimental trials, subjects
voided, were weighed, and then rested supine on a bed while a Teflon
catheter (Turumo, Tokyo, Japan) was placed into each antecubital vein.
After a basal blood sample was collected, the catheter for blood
sampling was kept patent by regular flushing with isotonic saline. The
second catheter was fitted with a three-way stopcock to allow for a
primed (3.3 mmol), continuous (~4.4 µmol/min) infusion of
[6,6-2H]glucose (Cambridge Isotope Laboratories,
Cambridge, MA), commencing 2 h before exercise and maintained
throughout the 2 h of steady-state exercise.
Subjects cycled for 2 h at 70%
O2 peak and then completed a 4 kJ/kg
body wt time trial as quickly as possible (based on weight recorded at
the 1st trial). The subjects were asked to drink 400 ml of a beverage
at the start of exercise and another 230 ml every 15 min for the entire
steady-state exercise period. For the two CHO trials, one in the
follicular phase (FG) and one in the luteal phase (LG), the drink
consisted of a 6% glucose solution containing 0.75 µCi of
[6-3H]glucose per gram of glucose. In the control trials,
denoted as FC and LC in the follicular and luteal phases, respectively, the drink consisted of water artificially sweetened with aspartame (placebo). Trials were randomized and double-blind as to which beverage
was being consumed.
Analysis.
Collected venous blood samples (~1.5 ml) were immediately placed into
precooled tubes containing EGTA and glutathione as a preservative and
centrifuged to separate the plasma. Samples were then stored at
80°C for later spectrophotometric assay analysis for free fatty
acid (FFA-C test kit, Wako Chemicals, Neuss, Germany). Remaining whole
blood was placed in precooled fluoride heparin tubes (~2 ml/tube),
spun to extract the plasma, and stored at
80°C for later analysis.
Glucose and lactate were analyzed using an automated method
(Electrolyte Metabolite Laboratory, Radiometer, Copenhagen, Denmark).
Glycerol was measured using a fluorometric assay linked to NADH.
Glucagon was analyzed by RIA, as previously described (1).
Insulin and the sex steroids were measured using commercially available
double-antibody RIA kits (Pharmacia & Upjohn and Diagnostic Products,
respectively). An additional aliquot of plasma was analyzed for
[6,6-2H]glucose enrichment and specific activity of
[6-3H]glucose, as previously described (28).
Additionally, an aliquot of the infusate and an aliquot of the ingested
drink were analyzed for percent enrichment and specific activity,
respectively, for comparison with the results from the blood samples.
All analyses had been previously performed in our laboratory
(coefficient of variation <10%).
At 15-min intervals throughout the steady-state exercise, heart rate
was recorded (Electro, Polar), and expired gas was collected into a
Douglas bag. Expired gas samples were analyzed for O2 and CO2 concentration (Applied Electrochemistry S-3A/II and
CD-3A, Ametek, Pittsburgh, PA). The analyzers were calibrated using
commercial gases of known composition. The volume of expired air was
measured on a Parkinson-Cowan gas meter calibrated against a Tissot
spirometer. O2 uptake, respiratory exchange ratio, and
ventilation were determined using conventional equations. With the
assumption of a nonprotein respiratory quotient (30), an
estimation of the whole body CHO and fat oxidation was calculated by
indirect calorimetry.
Statistics.
All statistical comparisons were made using two- or three-way ANOVA
tables, as appropriate, with significance set at P < 0.05. Specific differences were located with a Newman-Keuls
F-test post hoc comparison. All data statistics were
compared using the Statistica software package, and data are reported
as means ± SE.
 |
RESULTS |
Subject characteristics.
The subject characteristics are presented in Table
1. Plasma E2 and progesterone
concentrations (Fig. 1) confirmed the
menstrual cycle phases, with a 2.5-fold increase in E2
(P < 0.01) and an 18-fold increase in progesterone
(P < 0.01) in the luteal compared with the follicular
phase. As expected, no differences were found in hormone levels between
control and glucose trials conducted in the same phase of the menstrual
cycle. Heart rate was not different at any point between trials (data
not shown). Characteristics for each of the four experimental trials
are presented in Table 2. Because we
assume that glucose rate of disappearance (Rd) during
exercise was approximately equal to the amount of glucose oxidized, we
were able to obtain an indirect measure of glucose oxidation and CHO
oxidation derived from other sources (i.e., glycogen)
(20). There were no differences in the average percent
O2 peak or total energy expenditure in
any of the trials. The total percent contribution of CHO was higher in
FC than in LC (P < 0.05) and was even greater in the
glucose trials (P < 0.05). Additionally, the ingestion
of glucose throughout exercise increased the percent contribution of
plasma glucose vs. other CHO compared with both control trials
(P < 0.05). There was also a trend for increased
contribution of plasma glucose in FC compared with LC; however, this
did not reach statistical significance (P = 0.058).

View larger version (18K):
[in this window]
[in a new window]
|
Fig. 1.
Plasma 17 -estradiol (A) and progesterone
(B) levels before the commencement of exercise. CHO,
carbohydrate. *Different (P < 0.01) from follicular
phase.
|
|
Plasma hormones and metabolites.
There were no differences in plasma glucose or lactate concentrations
before the commencement of exercise in any of the experimental trials
(Fig. 2). Glucose ingestion increased
plasma glucose levels to above resting values (P < 0.05) at all time points during exercise in the follicular and luteal
phases. During both control trials (FC and LC) there was a gradual
decline in plasma glucose levels that became significantly different
from rest at 120 min of exercise. Menstrual cycle phase had no effect
on plasma glucose concentrations during exercise in the placebo trials;
however, in the glucose trials, plasma glucose was higher at 30 and 60 min in FG than in LG. Plasma lactate concentrations were elevated above
resting values throughout exercise (P < 0.05), but
neither glucose ingestion nor menstrual cycle phase had any effect.

View larger version (21K):
[in this window]
[in a new window]
|
Fig. 2.
Plasma glucose (A) and lactate (B)
concentrations at rest and during 2 h of cycling exercise in
different phases of the menstrual cycle with or without a CHO beverage.
F, follicular phase; L, luteal phase; C, control; G, glucose ingestion.
*Different (P < 0.05) from resting values from that
point onward. Difference (P < 0.05) between FC and
LC at the same time point. Difference (P < 0.05)
between FG and LG at the same time point. §Difference
(P < 0.05) between FC and FG at the same time point.
¶Differences (P < 0.05) between LC and LG
at the same time point.
|
|
Plasma FFA and glycerol levels were also similar before the
commencement of exercise in all trials (Fig.
3). Plasma FFA concentrations were
increased compared with resting values (P < 0.05) at
60 and 90 min of exercise in the FC and LC trials, respectively, to the end of steady-state exercise (120 min). Exercise also increased plasma
glycerol levels (P < 0.05) to above resting values at
30 min (FC), 60 min (FG and LC), and 90 min (LG). Plasma FFA and glycerol concentrations were elevated (P < 0.05) in FC
compared with LC at all time points during exercise. Ingestion of
glucose during exercise suppressed plasma FFA and glycerol levels in
the 2nd h of exercise (P < 0.05) compared with the
control trial in both phases of the menstrual cycle.

View larger version (20K):
[in this window]
[in a new window]
|
Fig. 3.
Plasma free fatty acid (FFA, A) and glycerol
(B) concentrations at rest and during 2 h of cycling
exercise in different phases of the menstrual cycle with or without a
CHO beverage. See Fig. 2 legend for explanation of symbols.
|
|
Although plasma insulin values were not significantly different before
exercise, there was a tendency (P = 0.07) for higher basal plasma insulin in the luteal phase (Fig.
4). There was a phase effect at 30 min of
exercise in the glucose trials, with insulin being elevated
(P < 0.05) in FG compared with LG; however, for the
remainder of the steady-state exercise, there were no further phase
effects. As expected, insulin levels were elevated (P < 0.05) in both glucose trials compared with control trials at all
time points during exercise.

View larger version (17K):
[in this window]
[in a new window]
|
Fig. 4.
Plasma insulin (A) and glucagon (B)
concentrations at rest and during 2 h of cycling exercise in
different phases of the menstrual cycle with or without a CHO beverage.
See Fig. 2 legend for explanation of symbols.
|
|
There was a significant difference in plasma glucagon values between
the follicular (FC and FG) and luteal (LC and LG) phases at rest (Fig.
4). These differences persisted in the control trials (FC and LC)
throughout exercise; however, they were no longer evident during
exercise in FG and LG. As expected, the ingestion of glucose
blunted the rise in plasma glucagon levels in FC and LC at the end of exercise.
Glucose kinetics.
In the fasted state (control trials), hepatic glucose production (HGP)
during exercise was assumed to be equal to total rate of appearance
(Ra) of glucose, inasmuch as minimal glucose is available
from other sources (37). The data in Fig.
5 demonstrate that total glucose
Ra was increased above resting values (P < 0.05) from the onset of exercise in all trials. This was a result of
increased HGP in the control trials (FC and LC); however, in the
glucose trials (FG and LG), HGP was suppressed (P < 0.05) compared with control trials and resting values, and the
Ra was maintained primarily by absorption of glucose by the
gut. As expected, despite the suppressed HGP, total glucose
Ra was higher in the glucose trials (P < 0.05) than in the control trials regardless of menstrual cycle phase.
Interestingly, HGP and glucose Ra were elevated
(P < 0.05) beginning at 30 and 75 min, respectively, in FC compared with LC. Although HGP was higher and gut Ra
was lower in LG than in FG at 15 min of exercise (P < 0.05), there were no other phase effects on total Ra, gut
Ra, or HGP with the ingestion of glucose during exercise.

View larger version (23K):
[in this window]
[in a new window]
|
Fig. 5.
Total rate of glucose appearance (Ra,
A) and hepatic glucose production (HGP, B) at
rest and during 2 h of cycling exercise in different phases of the
menstrual cycle with or without a CHO beverage. See Fig. 2 legend for
explanation of symbols.
|
|
Glucose Rd and the metabolic clearance rate (MCR) were
increased during exercise in all trials (Fig.
6). Glucose Rd was increased during the glucose trials compared with the control trials
(P < 0.05) starting at 30 and 60 min in the follicular
and luteal phases, respectively. During the control trials,
Rd was significantly higher (P < 0.05) in
FC than in LC during the 2nd h of exercise. These phase effects were
not seen in glucose trials (FG and LG). Although there were no specific
differences in MCR, there was a phase × drink interaction, with
glucose ingestion increasing MCR and higher MCR in FC than in LC
(P < 0.05).

View larger version (20K):
[in this window]
[in a new window]
|
Fig. 6.
Glucose rate of disappearance (Rd,
A) and metabolic clearance rate (MCR, B) at rest
and during 2 h of cycling exercise in different phases of the
menstrual cycle with or without a CHO beverage.
Phase × drink interaction (P < 0.05); see Fig. 2 legend for explanation of other symbols.
|
|
Performance.
Figure 7 illustrates the performance
times for the four trials, demonstrating that glucose ingestion
decreased (P < 0.05) the time taken to complete the
set amount of work, regardless of menstrual cycle phase (19 and 26%
improvement in FG and LG compared with FC and LC, respectively,
P < 0.05). Additionally, subjects completed the work
faster in FC than in LC (13% improvement, P < 0.05).
Interestingly, this menstrual phase performance difference was
abolished by the ingestion of glucose during exercise.

View larger version (18K):
[in this window]
[in a new window]
|
Fig. 7.
Performance times for the 4 kJ/kg body wt time trial
completed after 2 h of cycling exercise. See Fig. 2 legend for
explanation of symbols.
|
|
 |
DISCUSSION |
The results of the study demonstrate that variations in the
ovarian hormone levels throughout the menstrual cycle do alter exercise
metabolism, but only in the absence of glucose ingestion. Indeed, as
the control trials progressed, differences became more pronounced,
indicating that as CHO sources became more depleted, the influence of
the sex steroids on exercise metabolism became more evident. This was
further exemplified by the lack of differences between FG and LG
trials. When CHO was adequately supplied throughout exercise, the
cycling levels of E2 and progesterone had only a minimal effect.
Glucose kinetic data revealed that, during control trials,
Ra, HGP, and Rd were lower in LC, particularly
during the 2nd h of exercise. These findings were similar to another
recent study (39), despite differences in the exercise
protocol. Subjects in the previous study (39) exercised at
much lower intensities, when larger differences in substrate oxidation
might be expected. Recently, two other studies have investigated the
effect of E2 on glucose kinetics: one examined treatment of
amenorrheic women with transdermal E2 patches
(33), and the other gave short-term oral E2
treatments to men (8). In both studies, E2
reduced Ra and Rd; however, results from these
studies must be carefully interpreted. Amenorrhea itself brings about
metabolic changes, which may alter responses to exercise
(23) and could additionally change the response to
artificially increased levels of E2. Furthermore, the
treatment of amenorrhea with E2 resulted in plasma
E2 levels that were still >10-fold less than those seen in
normally menstruating women and, therefore, may not be relevant to
eumenorrheic athletes. Correspondingly, although treating men with
E2 can provide interesting results because of differences
in receptor populations and a number of other physiological variables,
men and women often respond differently to changes in the sex steroids
(17). Thus, despite the temptation to relate the decreased
Ra and Rd during the luteal phase in this study
to elevated E2 levels, this has not been experimentally confirmed.
The percent contribution of CHO and fat to total substrate oxidation
was significantly different between the control trials. During FC, the
percent contribution from CHO was greater and that from fat was less
than during LC. Additionally, glucose Rd was greater
throughout exercise in FC than in LC, and this corresponded with a
strong tendency (P = 0.058) for greater glucose
oxidation. This small increase in Rd resulted in a decrease
in fat oxidation rather than an attenuated use of other CHO (i.e.,
glycogen). However, glycogen was not directly measured. In a recent
study that did directly measure muscle glycogen use, Hackney
(16) demonstrated that glycogen use is decreased in the
luteal phase compared with the follicular phase during 60 min of
cycling exercise. Discrepancies in these results are probably due to
the sensitivity of whole body pulmonary and tracer-determined measures
to derive glycogen oxidation, which is a limitation in this study.
However, differences could also be due to the duration of exercise; in
this study, differences in Rd were found after 60 min of
exercise. This could indicate that, during FC, as muscle glycogen
stores become depleted, glucose uptake is increased, allowing for
sparing of glycogen during the later stages of exercise. Interestingly,
in this study, differences in substrate oxidation between the two
phases lie primarily in glucose uptake and utilization and lipid
oxidation. This could result from preferential oxidation of one
substrate over the other or from preferential uptake of glucose or FFA
from circulation. From these results, it is impossible to determine whether the source of fat for oxidation was intramuscular triglycerides or uptake of plasma FFA. Given the recent findings of plasma membrane and cytosolic fatty acid transport proteins (5), it would
be interesting to further investigate menstrual phase effects on lipid
kinetics during exercise.
The metabolic effects of E2 have been a subject of great
interest, particularly in lipid synthesis and oxidation. Accordingly, the increased reliance on fat oxidation observed during the luteal phase has been readily attributed to the concurrent elevation in
E2. However, during the luteal phase, there is a
proportionately much greater increase in progesterone concentrations,
which itself could have metabolic effects. Progesterone has often been
reported to have an "antiestrogenic" effect, which has been
observed in CHO and lipid metabolism (18, 34). Animal
studies have demonstrated that E2 spares glycogen during
prolonged exercise, likely due to increased lipid availability and
oxidation (22). Unfortunately, these studies did not
investigate the effect of progesterone alone or in combination with
E2. Interestingly, E2 has also been
demonstrated to have beneficial effects in CHO metabolism, increasing
glucose uptake stimulated by insulin (31) and exercise
(7). Although progesterone alone has often been reported
as having no distinct effects on lipid or CHO metabolism in
ovariectomized animals (31), when progesterone and
E2 have been administered in combination, progesterone has
inhibited the beneficial effect of E2 on lipid availability
and oxidation (18) and CHO metabolism (31).
These combined findings suggest that the menstrual phase effects on exercise metabolism in the placebo trials could result from elevated progesterone levels in LC inhibiting the beneficial effects of E2 on glucose uptake, thereby forcing the contracting
muscles to increase fat oxidation. CHO oxidation requires less
O2 per joule than fat and is the substrate of choice during
exercise of moderate to high intensity (32). Because the
exercise intensity used in this investigation (~70%
O2 peak) was at a level at which CHO
metabolism may become exponentially more important to energy
production, it is likely that glucose uptake would play a greater role
in this protocol. Furthermore, increased glucose uptake could be
responsible for the increase in performance during the FC trials. The
time trial protocol allowed athletes to determine their own pace during
the completion of the set amount of work (simulating a race situation).
Every subject performed faster in FC than in LC, indicating that they
were able to maintain a higher intensity of exercise throughout the
time trial. As reliance on CHO increases with exercise intensity
(32), it seems logical that an increased ability for
glucose uptake during FC would benefit performance. Interestingly,
we recently demonstrated that progesterone decreases total GLUT-4
content in the red vastus of rats (unpublished data), which would
restrict glucose uptake during the luteal phase, particularly during
increased metabolic stress. Although greater time to exhaustion has
been previously observed in the luteal than in the follicular phase
(29), inasmuch as subjects must ride at a previously
determined workload, an increased ability for glucose uptake may not be
as advantageous. However, even this phase effect seems to also be
contingent on nutritional status, inasmuch as time to fatigue was
similar with glucose ingestion (3).
Further evidence to suggest the preferential oxidation of CHO at the
exercise intensity used in this study is the reduction in fat oxidation
with glucose ingestion. This could be due to elevated insulin levels
suppressing lipolysis (38), thereby decreasing lipid
availability; however, it could also be the result of increased CHO
availability. When plasma glucose levels are elevated, there is a
larger concentration gradient for glucose to move into the cell,
perhaps limiting the effect of the ovarian hormones on glucose
transport. Although plasma glucose levels were similar between FC and
LC, they were significantly lower than during the glucose trials,
perhaps increasing the importance of glucose transport capacity.
Notably, the difference in glucose Rd between FC and LC
persisted throughout the 2nd h of exercise, even in the presence of
similar plasma glucose concentration. This resulted in a lower MCR in
LC (P < 0.05), suggesting that the reduced glucose
disposal was due to a decrease in glucose transport per se and not to
relative hypoglycemia. Although glucose Ra and
Rd were statistically different in FC and LC only during the 2nd h of exercise, HGP was higher in FC than in LC beginning at 30 min. This is perhaps indicative of subtle differences in glucose
Ra and Rd before 60 min of exercise. Finally,
elevation of glucose Rd during the 2nd h of exercise in FC
compared with LC supports the hypothesis that the metabolic changes
resulting from variations in the ovarian hormones were caused by
progesterone inhibiting the effect of E2 on glucose uptake.
Ingestion of glucose obliterated most of the metabolic differences
between follicular and luteal phase trials; however, it produced some
interesting effects on glucose kinetics. This is the first study to
investigate glucose kinetics during CHO ingestion in women, despite
previously observed gender differences in CHO metabolism during
exercise (35, 36). Ingestion of glucose during exercise
resulted in an increase in glucose Rd, but most interestingly, it also resulted in an increase in plasma glucose oxidation. The increase in the percent contribution to energy expenditure of plasma glucose resulted in a shift of substrate oxidation from fat to CHO in FG and LG compared with control trials. Additionally, it resulted in a small, but significant, decrease in the
oxidation of other CHO compared with control trials, possibly indicating a glycogen-sparing effect. These results differ from those
previously seen in men (20, 28), where the contribution of
plasma glucose to total CHO oxidation was not substantial. It is
interesting to note that a similar exercise/CHO ingestion protocol on
men conducted in our laboratory demonstrated that plasma glucose
contributed only 8-11% to substrate oxidation during CHO
ingestion (12). Conversely, in the present study, there was a 9-12% contribution during the control trials, and this
increased to 19% in the glucose trials. Furthermore, despite glucose
ingestion altering glucose kinetics in men, it has been demonstrated to have no effect on glycogen use during exercise (13, 20).
Although this gender comparison is anecdotal, this is not the first
study to observe a greater glucose flux in women than in men.
Friedlander et al. (14) found that, after training, a
higher percentage of total CHO oxidation was derived from plasma
glucose in women and that this likely resulted in glycogen sparing
compared with their male counterparts. These findings suggest that
trained women have a greater capacity to utilize plasma glucose during
exercise and, therefore, may derive a greater benefit from CHO
ingestion than that previously seen in men. Indeed, a previous study
from our laboratory using a time trial protocol found that glucose ingestion resulted in a 7% increase in performance in men
(2), whereas this study reports a 19-26% increase in
performance, notwithstanding the differences in time trial protocols
when these two studies are compared.
The effect of menstrual cycle phase on exercise performance is of
particular importance to female athletes. This study has demonstrated
that, in the fasted state, women perform better in the follicular than
in the luteal phase of the menstrual cycle. However, the ingestion of
glucose obliterated this phase difference, illustrating that, in the
postprandial state, the metabolic stress of endurance exercise is not
sufficient to elicit menstrual phase effects. This could possibly
explain some of the discrepancy in the literature with regard to the
effect of menstrual cycle phase on exercise performance. In a recent
study reporting an absence of metabolic differences between the
follicular and luteal phases during endurance exercise to fatigue, the
trials were conducted in the postprandial state (3).
Additionally, although Kanaley et al. (21) also reported
no effect of menstrual phase during 90 min of endurance exercise, they
investigated only substrate utilization based on the nonprotein
respiratory quotient and did not have a performance component. This
result is similar to the results observed in this study up to 60 min;
however, we found that glucose kinetics and substrate oxidation did
indeed vary, particularly during the 2nd h of exercise. On the basis of
the results from this study, female athletes preparing for races during the luteal phase of their menstrual cycle should ensure adequate CHO
consumption during an endurance event. Finally, these results are also
important for researchers investigating metabolic responses to exercise
in women, inasmuch as they demonstrate that variations in exercise
metabolism induced by the menstrual cycle can be minimized by ensuring
an adequate CHO source throughout endurance exercise.
 |
ACKNOWLEDGEMENTS |
The authors acknowledge the assistance of Dr. Emma Starritt and
Rebecca Starkie and thank them for their contribution.
 |
FOOTNOTES |
This study was supported by a grant from the Gatorade Sport Science Institute.
Address for reprint requests and other correspondence: M. A. Febbraio, Exercise Physiology and Metabolism Laboratory, Dept. of
Physiology, The University of Melbourne, Parkville, Victoria 3010, Australia (E-mail: m.febbraio{at}physiology.unimelb.edu.au).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 16 March 2001; accepted in final form 14 May 2001.
 |
REFERENCES |
1.
Alford, FP,
Bloodm SR,
and
Nabarro JD.
Glucagon levels in normal and diabetic subjects: use of a specific immunoabsorbent for glucagon radioimmunoassay.
Diabetologia
13:
1-6,
1977[ISI][Medline].
2.
Angus, DJ,
Hargreaves M,
Dancey J,
and
Febbraio MA.
Effect of carbohydrate or carbohydrate plus medium-chain triglyceride ingestion on cycling time trial performance.
J Appl Physiol
88:
113-119,
2000[Abstract/Free Full Text].
3.
Bailey, SP,
Zacher CM,
and
Mittleman KD.
Effect of menstrual cycle phase on carbohydrate supplementation during prolonged exercise to fatigue.
J Appl Physiol
88:
690-697,
2000[Abstract/Free Full Text].
4.
Bonen, A,
Haynes FJ,
Watson-Wright W,
Sopper MM,
Pierce GN,
Low MP,
and
Graham TE.
Effects of menstrual cycle on metabolic responses to exercise.
J Appl Physiol
55:
1506-1513,
1983[Abstract/Free Full Text].
5.
Bonen, A,
Luiken JJ,
Arumugam Y,
Glatz JF,
and
Tandon NN.
Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase.
J Biol Chem
275:
14501-14508,
2000[Abstract/Free Full Text].
6.
Brown, JB,
Blackwell LF,
Cox RI,
and
Holmes J.
Chemical and homogeneous enzyme immunoassays of urinary estrogens and pregnanediol and their glucuronides.
Prog Biol Clin Res
285:
119-138,
1988.
7.
Campbell SE and Febbraio MA. Effect of ovarian steroid hormones on
contraction-stimulated glucose uptake in rat skeletal muscle
(Abstract). ADS and ADEA Annual Scientific Meeting,
2000, p. 82.
8.
Carter, S,
McKenzie S,
Mourtzakis M,
Mahoney DJ,
and
Tarnopolsky MA.
Short-term 17
-estradiol decreases glucose Ra but not whole body metabolism during endurance exercise.
J Appl Physiol
90:
139-146,
2001[Abstract/Free Full Text].
9.
Coggan, AR,
and
Coyle EF.
Carbohydrate ingestion during prolonged exercise: effects on metabolism and performance.
Exerc Sport Sci Rev
19:
1-40,
1991[Medline].
10.
Davis, JM,
and
Bailey SP.
Possible mechanisms of central nervous system fatigue during exercise.
Med Sci Sports Exerc
29:
45-57,
1997[ISI][Medline].
11.
De Bruyn Prevost, P,
Masset C,
and
Sturbois X.
Physiological response from 18-25 years women to aerobic and anaerobic physical fitness tests at different periods during the menstrual cycle.
J Sports Med Phys Fitness
24:
144-148,
1984[ISI][Medline].
12.
Febbraio, MA,
Chiu A,
Angus DJ,
Arkinstall MJ,
and
Hawley JA.
Effects of carbohydrate ingestion before and during exercise on glucose kinetics and performance.
J Appl Physiol
89:
2220-2226,
2000[Abstract/Free Full Text].
13.
Febbraio, MA,
Keenan J,
Angus DJ,
Campbell SE,
and
Garnham AP.
Preexercise carbohydrate ingestion, glucose kinetics, and muscle glycogen use: effect of the glycemic index.
J Appl Physiol
89:
1845-1851,
2000[Abstract/Free Full Text].
14.
Friedlander, AL,
Casazza GA,
Horning MA,
Huie MJ,
Piacentini MF,
Trimmer JK,
and
Brooks GA.
Training-induced alterations of carbohydrate metabolism in women: women respond differently from men.
J Appl Physiol
85:
1175-1186,
1998[Abstract/Free Full Text].
15.
Friedmann, B,
and
Kindermann W.
Energy metabolism and regulatory hormones in women and men during endurance exercise.
Eur J Appl Physiol
59:
1-9,
1989.
16.
Hackney, AC.
Influence of oestrogen on muscle glycogen utilization during exercise.
Acta Physiol Scand
167:
273-274,
1999[ISI][Medline].
17.
Haffner, SM,
and
Valdez RA.
Endogenous sex hormones: impact on lipids, lipoproteins, and insulin.
Am J Med
98:
40S-47S,
1995[Medline].
18.
Hatta, H,
Atomi Y,
Shinohara S,
Yamamoto Y,
and
Yamada S.
The effects of ovarian hormones on glucose and fatty acid oxidation during exercise in female ovariectomized rats.
Horm Metab Res
20:
609-611,
1988[ISI][Medline].
19.
Hornum, M,
Cooper DM,
Brasel JA,
Bueno A,
and
Sietsema KE.
Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women.
J Appl Physiol
82:
1946-1951,
1997[Abstract/Free Full Text].
20.
Jeukendrup, AE,
Wagenmakers AJ,
Stegen JH,
Gijsen AP,
Brouns F,
and
Saris WH.
Carbohydrate ingestion can completely suppress endogenous glucose production during exercise.
Am J Physiol Endocrinol Metab
276:
E672-E683,
1999[Abstract/Free Full Text].
21.
Kanaley, JA,
Boileau RA,
Bahr JA,
Misner JE,
and
Nelson RA.
Substrate oxidation and GH responses to exercise are independent of menstrual phase and status.
Med Sci Sports Exerc
24:
873-880,
1992[ISI][Medline].
22.
Kendrick, ZV,
and
Ellis GS.
Effect of estradiol on tissue glycogen metabolism and lipid availability in exercised male rats.
J Appl Physiol
71:
1694-1699,
1991[Abstract/Free Full Text].
23.
Lamon-Fava, S,
Fisher EC,
Nelson ME,
Evans WJ,
Millar JS,
Ordovas JM,
and
Schaefer EJ.
Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.
J Clin Endocrinol Metab
68:
17-21,
1989[Abstract].
24.
Landgren, BM,
Unden AL,
and
Diczfalusy E.
Hormonal profile of the cycle in 68 normally menstruating women.
Acta Endocrinol
94:
89-98,
1980[ISI][Medline].
25.
Lavoie, JM,
Dionne N,
Helie R,
and
Brisson GR.
Menstrual cycle phase dissociation of blood glucose homeostasis during exercise.
J Appl Physiol
62:
1084-1089,
1987[Abstract/Free Full Text].
26.
Lebrun, CM,
McKenzie DC,
Prior JC,
and
Taunton JE.
Effects of menstrual cycle phase on athletic performance.
Med Sci Sports Exerc
27:
437-444,
1995[ISI][Medline].
27.
Lynch, NJ,
and
Nimmo MA.
Effects of menstrual cycle phase and oral contraceptive use on intermittent exercise.
Eur J Appl Physiol
78:
565-572,
1998.
28.
McConell, G,
Fabris S,
Proietto J,
and
Hargreaves M.
Effect of carbohydrate ingestion on glucose kinetics during exercise.
J Appl Physiol
77:
1537-1541,
1994[Abstract/Free Full Text].
29.
Nicklas, BJ,
Hackney AC,
and
Sharp RL.
The menstrual cycle and exercise: performance, muscle glycogen, and substrate responses.
Int J Sports Med
10:
264-269,
1989[ISI][Medline].
30.
Peronnet, F,
and
Massicotte D.
Table of nonprotein respiratory quotient: an update.
Can J Sport Sci
16:
23-29,
1991[ISI][Medline].
31.
Puah, JA,
and
Bailey CJ.
Effect of ovarian hormones on glucose metabolism in mouse soleus muscle.
Endocrinology
117:
1336-1340,
1985[Abstract].
32.
Romijn, JA,
Coyle EF,
Sidossis LS,
Gastaldelli A,
Horowitz JF,
Endert E,
and
Wolfe RR.
Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.
Am J Physiol Endocrinol Metab
265:
E380-E391,
1993[Abstract/Free Full Text].
33.
Ruby, BC,
Robergs RA,
Waters DL,
Burge M,
Mermier C,
and
Stolarczyk L.
Effects of estradiol on substrate turnover during exercise in amenorrheic females.
Med Sci Sports Exerc
29:
1160-1169,
1997[ISI][Medline].
34.
Rushakoff, RJ,
and
Kalkhoff RK.
Effects of pregnancy and sex steroid administration on skeletal muscle metabolism in the rat.
Diabetes
30:
545-550,
1981[ISI][Medline].
35.
Tarnopolsky, MA,
Atkinson SA,
Phillips SM,
and
MacDougall JD.
Carbohydrate loading and metabolism during exercise in men and women.
J Appl Physiol
78:
1360-1368,
1995[Abstract/Free Full Text].
36.
Tarnopolsky, MA,
Bosman M,
Macdonald JR,
Vandeputte D,
Martin J,
and
Roy BD.
Postexercise protein-carbohydrate and carbohydrate supplements increase muscle glycogen in men and women.
J Appl Physiol
83:
1877-1883,
1997[Abstract/Free Full Text].
37.
Wahren, J,
Felig P,
Ahlborg G,
and
Jorfeldt L.
Glucose metabolism during leg exercise in man.
J Clin Invest
50:
2715-2725,
1971[ISI][Medline].
38.
Wolfe, RR,
Nadel ER,
Shaw JH,
Stephenson LA,
and
Wolfe MH.
Role of changes in insulin and glucagon in glucose homeostasis in exercise.
J Clin Invest
77:
900-907,
1986[ISI][Medline].
39.
Zderic, TW,
Coggan AR,
and
Ruby BC.
Glucose kinetics and substrate oxidation during exercise in the follicular and luteal phases.
J Appl Physiol
90:
447-453,
2001[Abstract/Free Full Text].
Am J Physiol Endocrinol Metab 281(4):E817-E825
0193-1849/01 $5.00
Copyright © 2001 the American Physiological Society