Gender influence on jejunal migrating motor complex
Nec
p
Aytu
1,
Adnan
G
ral1,
Ne
e
meryüz1,
Feruze Y.
Enç1,
Nural
Bek
ro
lu2,
Güler
Akta
3, and
Nef
se B.
Ulusoy1
1 Division of Gastroenterology, Department of Internal
Medicine, and 2 Department of Biostatistics, University of
Marmara School of Medicine, 81326 Haydarpa
a, Istanbul; and
3 Department of Physics, Bo
aziçi University, 80815 Istanbul, Turkey
 |
ABSTRACT |
The role
of gender and the menstrual cycle in small bowel motility has not been
clearly elucidated. Jejunal motility was recorded with a nasojejunal
catheter incorporating five solid-state pressure transducers in
ambulatory menstruating women and men of comparable age over 24 h.
All women were studied twice, in the early follicular (early-F) and
midluteal (mid-L) phases of the menstrual cycle, verified by
determining serum levels of gonadal steroids and gonadotropins. The
propagation velocity of phase III was slow and the contraction
amplitude was high in both menstrual cycle phases compared with men,
and these parameters were correlated with serum estrogen levels in the
mid-L phase. In the early-F phase, migrating motor complex (MMC) cycle
duration during sleep was long compared with other groups and
positively correlated with estrogen concentrations, whereas in the
mid-L phase MMC cycle duration during sleep was negatively correlated
with serum progesterone levels. In all groups, the frequency of phase
III contractions was low and the intercontractile interval measured
from pressure peak to peak was long during sleep compared with the
awake state. Postprandial motility did not display gender difference in
any parameter examined. The results demonstrate that the majority of
patterns of motility are similar in menstruating women and men, whereas
certain aspects of the MMC, most conspicuously propagation velocity and
phase III contraction amplitude, differ. We have also documented
circadian variation of phase III contraction frequency in both women
and men.
circadian variation; menstrual cycle; ambulatory motility; estrogen; progesterone
 |
INTRODUCTION |
MOTILITY OF THE SMALL
BOWEL is modulated by biological factors such as fasting
(13, 15, 17), caloric content of nutrients (25), sleep (12, 17, 20), and aging
(14, 17). The role of gender as a modifier of small bowel
motility in humans is controversial and has not been studied in depth.
The issue is relevant because the definition of intestinal motility
aberrations in disease states requires the role of gender to be
elucidated (13). Previous studies in healthy subjects of
various age groups reported similar intestinal motor activity between
women and men (14, 17). However, an antroduodenal
ambulatory study during wakefulness documented shorter migrating motor
complex (MMC) periods in women compared with men (32). The
aforementioned studies were performed without controlling the menstrual
cycle. In a recent study of duodenojejunal motility, women in the
follicular phase were found to exhibit motor activity similar to that
of men (26). On the other hand, Knight et al.
(18) demonstrated attenuated postprandial antral
contractile activity in the follicular phase of women compared with men
(18).
Ovarian steroid hormones and pregnancy are suggested to modulate
electromechanical behavior of the gastrointestinal smooth muscle.
Gastrointestinal muscle strips obtained from pregnant mammals
(23) or subjected to progesterone administration (6, 19) exhibit decreased contractile response to cholinergic agents and to cholecystokinin. During pregnancy, lower esophageal sphincter pressure is low and orocecal transit is slow (1, 30). In menstruating women the gastric emptying rate of solids (9, 11,
16, 18) and colonic transit are slow compared with those in men
of similar age (9). Therefore, it is appropriate to consider the menstrual cycle in the investigation of motility related
to gender difference.
The aim of the present study was to investigate the role of gender and
the menstrual cycle on jejunal motor activity in a minimally altered
physiological setting. We chose to study early follicular (early-F) and
midluteal (mid-L) phases to make a comparison of relatively low
estrogen secretory state (days 2-6 of follicular phase) with the
high estrogen and progestogen secretory state (days 18-24 of
luteal phase). Considering that sleep substantially modulates motility
(13, 20), we also investigated whether such modulation is
operative in the phases of the cycle studied.
 |
METHODS |
Subjects.
Healthy menstruating women and men were recruited by advertisement to
participate in the study. Subjects with a previous history of
gastrointestinal symptoms, chronic diseases, or abdominal surgery other
than appendectomy were excluded from the study. None of the subjects
was on any medication. All women had regular menstrual cycles, and none
was taking oral contraceptives for at least 3 mo before the study.
Except for one woman all female subjects were nulliparous, and none of
them was lactating during the study.
The institutional ethics committee approved the study protocol, and
written informed consent was obtained from each subject. Women were
fully informed about the consequences of contraception and were advised
to refrain from sexual intercourse or to use condom contraception
during the study period. All women reported regular menstrual bleeding
after the study.
Measurement of jejunal motility.
Jejunal pressure events were recorded using a nasojejunal catheter (OD
4.7 mm; Konigsberg Instruments, Pasadena, CA) incorporating five
radiopaque solid-state pressure transducers. When properly placed in
the jejunum, the proximal transducer was situated at the duodenojejunal
flexure and the others were 2, 4, 14, and 24 cm distal to the proximal
transducer (designated as sensors 1-5 starting at the duodenojejunal flexure). Pressure was sampled at a rate
of 5 Hz from each transducer and was stored in digital form within a
portable 4-MB data logger (Super Logger, Sandhill Scientific, Highlands
Ranch, CO). The data were transferred to a computer for later display
and analysis. Before each study, the data logger was linked to a PC and
the transducers were calibrated by applying pressures of 0 and 100 mmHg
at room temperature.
Study design.
Each female subject underwent two 24-h ambulatory jejunal manometric
recordings, one during the early-F phase and the other during the mid-L
phase of the menstrual cycle. The order of the study was randomized.
Day 1 of the menstrual cycle was defined as the first day of vaginal
flow. Early-F phase was defined as the period from day 2 to day 6 of
the cycle, and the mid-L phase was defined as days 18-24 of the
cycle in a 28-day cycle period. The mid-L phase of each woman was
calculated by taking into account individual cycle periods and
estimating the oncoming first day of the cycle period.
Subjects were not allowed to smoke or consume alcoholic beverages for
at least 2 days before and during the study. All subjects were tube
naive. On the examination day, the subjects fasted after a light
breakfast and the intubation of the jejunum began at 3 PM. The
recording catheter was placed transnasally into the stomach after
topical anesthesia with 1% lidocaine (Abbot Laboratories) had been
applied to the nose and pharynx. The passage of the catheter tip beyond
the pylorus was observed using fluoroscopic guidance with a
freeze-frame facility. A latex balloon attached to the distal end of
the catheter was inflated with 5 ml of air to facilitate migration of
the assembly. When the correct position of the catheter was observed,
the latex balloon was deflated and the catheter was fastened to the
nose with adhesive tape. The subjects went home overnight to get
acclimatized to the catheter assembly, and they were asked to fast
after 12:00 AM. The next morning, the correct position of the
transducers was verified under fluoroscopy, and the recording commenced
between 8:30 and 11:30 AM. Ten milliliters of venous blood were
obtained from an antecubital vein of the women for determination of
serum concentrations of estradiol, progesterone, luteinizing hormone
(LH), and follicle-stimulating hormone (FSH). During the study subjects
continued their daily activities and avoided strenuous exercise.
Caloric and fiber content of meals were standardized (30 kcal · kg
1 · 24 h
1; 20%
protein, 40% carbohydrate, and 40% fat), and they were prepared in
the study premises according to the preference of the subject. Dairy
products were avoided in case of lactose intolerance. Two standard
solid meals were eaten: lunch between 11:30 AM and 12:30 PM and dinner
between 6:30 and 7:30 PM. Lunch consisted of one portion and dinner of
two portions of the total calories calculated for each subject. Females
consumed a median of 600 kcal (range 440-670 kcal) at lunch and
1,200 kcal (range 880-1,340 kcal) at dinner. The corresponding
values for males were 700 kcal (range 580-900 kcal) and 1,400 kcal
(range 1,160-1,800 kcal). Subjects ingested water ad libitum with
meals, and they refrained from eating and drinking at other times
during the study. In the case of thirst, small sips of water were
allowed. Most of the subjects ate lunch in the study premises and
dinner at home. All subjects went home to sleep and returned the next
morning for fluoroscopic verification of correct catheter position. The
recording was terminated after 24 h. Gonads were shielded during
each fluoroscopic verification, and the total duration of radiation
exposure was 2.0 ± 1.0, 2.5 ± 0.7, and 2.5 ± 1.0 min,
respectively, in the early-F and mid-L phases and in men.
Each subject kept a written diary of times of meals, water intake
between meals, retiring to bed to sleep, awakening, and defecation.
Subjects also activated the appropriate event buttons on the data
logger to designate the times of their activities on the motility
recording. Each subject was asked to estimate the time spent in bed
before falling asleep.
Analysis of jejunal manometric data.
Patterns of motor activity were analyzed visually and with a validated
small bowel motility program to identify individual pressure waves and
to calculate the frequency, amplitude, and motility index of
contractions (2). A threshold pressure of 10 mmHg and a
peak separation of 3.2 s were incorporated into the program for
recognition of individual contractions. The respective minimum and
maximum duration of a contraction were set at 2 and 9 s. Artifacts
appearing in all sensors were recognized visually and were excluded
from analysis. For the purpose of analysis, data were grouped into
periods of wakefulness and sleep. The sleep period was defined as the
moment when the subject retired to bed with the intention to sleep in
the evening until the time of waking. The remainder of the recording
was identified as the wakeful period. The recordings of women were
analyzed by two of the investigators who were unaware of the menstrual
phase during which the recording was performed.
The following criteria were used to recognize phases of the MMC:
1) phase I was recognized as motor quiescence characterized by less than three phasic events during a 10-min period; 2)
phase II was recognized as irregular phasic events that preceded phase III and occurred at a rate of more than two contractions in 10 min; and
3) phase III was recognized as regular phasic contractions of at least 2-min duration at the maximum rate for jejunum
(10-12/min) followed by phase I and migration to distal sensors
(17). Phasic events in the distal sensor (sensor
5) fulfilling all of the characteristics of phase III except
migration were treated as true phase III activity, and recordings of
this sensor were used for calculation of percentage contributions of
different phases of the MMC. In a few recordings, phasic events with
the characteristics of phase III were interrupted by periods of
quiescence or irregular activity of <30-s duration (17). If such pressure events culminated in an
uninterrupted phase III in the distal leads, this activity front was
considered as part of a single phase III; otherwise, they were
considered to be separate events. MMC cycle duration was defined as the
time elapsed between the commencement of two consecutive phase III activities. An average value to represent MMC cycle duration was obtained from all sensors. Phase II characteristics were studied in
recordings obtained from sensor 4. The fasting periods
before lunch, between lunch and dinner, and after dinner before sleep were compiled to represent the awake state fasting period. A phase III
occurrence was not required for designation of the fasting period
before lunch. At other times during the study, a fasting period was
defined as the time elapsed from the beginning of a phase III to the
beginning of a meal, as recognized by the postprandial motility
pattern, or to the termination of the study.
The recordings obtained from the third sensor, which was located ~4
cm distal to the duodenojejunal flexure, were used for analysis of
phase III features. The duration, frequency, and amplitude of pressure
waves were examined. The temporal features of contractions were
examined by calculating the frequency (number of pressure waves/min)
and by measuring the intercontractile interval. The intercontractile
interval was defined as the time interval between two consecutive
computer program-designated contractions measured from pressure peak to
pressure peak. Because the beginning and termination of phase III
displayed irregular pressure activity, the middle two-thirds portion of
phase III was used for this purpose (Fig.
1). Intervals were measured manually from
prints on which 10 mm of paper represented 3 s, using a ruler with
0.5 mm as the narrowest scale. To assess the accuracy of manual
reading, a second investigator measured intercontractile
intervals without knowing the composition of sample data that were
compiled by the unblinded investigator by randomly selecting two phase
IIIs in the awake period and two during sleep from the recordings of
four subjects in the early-F, mid-L, and male groups. The sample data
(793 intercontractile intervals) constituted ~10% of the total
intervals measured. The propagation velocity (PV) of a phase III
activity was defined as the distance between two pressure sensors
spaced 10 cm apart divided by the time taken for the onset of phase III
to transverse this distance (cm/min).

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Fig. 1.
An example of ambulatory manometric tracing of jejunal
phase III during wakefulness (A) and sleep (B)
from a woman in the early follicular (early-F) phase of the menstrual
cycle. Sensor 1 was at the duodenojejunal flexure, and the
others were distally spaced at 2, 4, 14, and 24 cm from sensor
1. Horizontal brackets on the 3rd channels (left)
represent 1-min tracings of phase III that are demonstrated on a
detailed time scale at right. Vertical bars in right
panels represent peak pressure of contraction, and the numbers
between them represent intercontractile intervals in seconds.
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Clustered contractions were recognized visually and were defined as
3-10 consecutive contractions occurring at a rate of
10-12/min preceded and followed by a 30-s quiescence
(13). The occurrence of clustered contractions during
phase II and the postprandial period at sensor 4 was examined.
The postprandial period was defined as the time interval between the
onset of irregular motor activity, as visually recognized and confirmed
by subject's diary, to the time when a phase III activity occurred.
The postprandial periods after lunch and dinner were analyzed
separately. Recordings of the fed pattern were divided into 10-min
epochs for computer-assisted calculation of mean amplitude, frequency,
and motility index of phasic events. Motility index was defined as all
areas under the curve of contractions in the region calculated by the
pressure from the baseline times the width on the baseline across the
contraction. The calculated data were normalized to a standard unit,
minutes (mmHg · s · min
1).
Hormone assays.
Serum was separated by centrifugation at 4°C and stored at
20°C
until assay. Serum concentrations of estradiol and progesterone were
determined by solid-phase chemiluminescent enzyme immunoassays (Immulite Estradiol and Immulite Progesterone; Diagnostics Products, Los Angeles, CA). The respective intra-assay coefficients of variation (CV) for estradiol and progesterone assays were 12 and 9%, whereas the
respective interassay CV were 13 and 10%. Serum concentrations of LH
and FSH were measured by using solid-phase two-site chemiluminescent enzyme immunometric assays (Diagnostics Products).
Statistical analysis.
The data are presented as means ± SD or medians (range) unless
stated otherwise. To represent each subject by a single value, a median
or a mean was obtained depending on the distribution of the data. Hence
the group means represent unweighted means or medians. Comparisons
within and between groups were obtained by using paired and
unpaired t-tests, respectively. Wilcoxon signed-rank test or
Mann-Whitney test was used for comparing nonparametric data. For
comparison of discrete variables the
2-test with Yates
correction as appropriate was used. The relationship between female
reproductive hormone concentrations (independent variable) and motility
parameters (dependent variable) was estimated by using Pearson's
correlation test.
The data representing MMC cycle length and propagation velocity of
phase III were analyzed for estimation of variation between and within
subjects by using the ANOVA model. The variance components between
(sb2) and within
(sw2) subjects were used to estimate the
variance within subjects as a percentage of the total variance
(Vw):
sw2/(sb2 + sw2) × 100 (15).
To estimate the degree of agreement between the two investigators in
the measurement of intercontractile interval the "limits of
agreement" method was used as described by Bland and Altman (4). Accordingly, the mean difference
(
) ± 2 SD displayed by the values of two groups
gives the limits of agreement and the 95% confidence intervals
indicate the precision of the estimate. Statistical significance was
defined as P < 0.05.
 |
RESULTS |
Thirty-six menstruating women and twenty-one men agreed to
participate in the study. Twenty-five women and ten men were excluded for various reasons such as failure to pass the catheter beyond the
pylorus or through the nasal cavity, antral migration of the catheter,
inappropriate serum female gonadal hormone levels for the menstrual
phase to be studied or irregular menses, and equipment failure. Hence,
11 menstruating women (mean age 22.0 ± 2.9 yr) and 11 men (mean
age 22.0 ± 3.3 yr) completed the study. The mean duration
of the menstrual period in the female study groups was 28.5 ± 1.7 days. Thus mid-L phase was studied during days 19-24 of the
menstrual period. Mid-L phase was the first study in seven women. The
two studies were separated by a median of 20 days, and the range was
7-167 days.
The respective median serum estradiol and progesterone levels in the
mid-L phase were 2.1 (0.6-6.1)- and 16 (2.3-56)-fold higher
than the respective levels observed in the early-F phase, and all
hormone concentrations were within the appropriate ranges of the phases
studied (Ref. 21; Table 1).
In the mid-L phase, the median serum FSH level was suppressed
characteristically for the luteal phase.
The mean recording times of 23.8 ± 0.4, 23.7 ± 0.5, and
24.1 ± 0.4 h in the early-F phase, mid-L phase, and male
groups, respectively, were not significantly different from each other.
Estimated delay to sleep was ~15-25 min. The quality of sleep
was reported generally as good.
Fasting motor activity.
The mean duration of fasting motor activity in the awake state was not
significantly different between groups or compared with the fasting
motor activity during sleep (Table 2).
The respective number of MMC cycles identified in the early-F, mid-L,
and male groups were 87, 101, and 110 for the total study period. The
proportions of MMC cycles that occurred before lunch, between lunch and
dinner, after dinner, and the next day before termination of the
recording were similarly distributed between study groups
(
2-test; data not shown). One woman subject had complete
MMC cycles only during the mid-L phase while asleep. During sleep the
median MMC cycle in the early-F group was longer compared with the
mid-L and male groups (Table 3).
Within-subject variance of the MMC cycle duration as a percentage of
total variance is depicted in Table 4.
Phase III characteristics.
The respective numbers of phase IIIs observed in the awake period and
during sleep were 143 and 164. The mean phase III duration was similar
among groups, and there was no circadian variation (Table
5). The mean amplitude of pressure waves
was higher in women during wakefulness, but statistical significance
was not observed (Table 5). However, during sleep the respective mean amplitudes of 30.4 ± 4.2 and 31.4 ± 7.2 mmHg in the early-F
and mid-L groups were higher than the corresponding value of 25.3 ± 5.9 mmHg in the male group (P < 0.05) (Table
5).
In the awake period the mean frequency of phase III pressure waves in
all groups was higher than that observed during sleep (Table 5). In the
awake period the mean numbers of intercontractile intervals measured
were 112 ± 47, 103 ± 57, and 138 ± 77 in the early-F,
mid-L, and male groups, respectively. These values were not
significantly different from each other or from the corresponding values obtained during sleep except in the mid-L group, which contributed fewer data points in the wake state. The mean (±SD) intercontractile intervals in the wake state were 5.14 ± 0.23, 5.18 ± 0.23, and 5.18 ± 0.21 s in the early-F, mid-L,
and male groups, respectively, and these values were shorter than the
corresponding values obtained in the sleep period [early-F, 5.29 ± 0.23 s (P = 0.07); mid-L, 5.32 ± 0.22 s (P < 0.05); male 5.35 ± 0.29 s
(P < 0.01); Fig. 2]. As
described in METHODS, 793 intervals were independently
measured by two investigators to assess the degree of agreement. The
between the two measurements was 0.0385 s, and the
majority of data points were within the limits of agreement (
2 SD:
0.298 s; +2 SD: +0.375 s). The 95% confidence interval (CI) of the
mean difference was 0.027-0.050. The degree of agreement appears
to be acceptable because the upper limit of 0.027 of the CI is
relatively small considering the ~5-s duration of the
intercontractile interval. Thus phase III contractions appeared to
occur at a slower pace during sleep compared with the awake state.
These parameters displayed neither gender nor menstrual phase
difference. The frequency distribution of the male group is presented
in Fig. 3 as an example of the circadian
variation of phase III contraction intervals.

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Fig. 2.
Intercontractile interval of phase III contractions
during the early-F and midluteal (mid-L) phases and in men. The data
are derived from recordings of a sensor situated 4 cm distal to the
duodenojejunal flexure. The intercontractile interval was the time
measured from pressure peak to pressure peak. Data are means ± SE. During sleep, the intervals were longer compared with the awake
state. P = 0.07 vs. early-F awake; *P < 0.05 vs. mid-L awake; **P < 0.01 vs. awake men.
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Fig. 3.
Frequency distribution of the intercontracile interval of
phase III contractions in men. The intercontractile interval was the
time interval measured from pressure peak to pressure peak. The
frequency distribution curve during sleep is skewed to the right,
covering more intervals with longer duration compared with the curve
during the awake state.
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In each study group, PV between the proximal sensors (sensors 3 and 4) displayed a wide range among subjects and the
group means were not statistically different from each other both in the awake state and during sleep. On the other hand, PV values measured
from the distal sensors (sensors 4 and 5) showed
a relatively narrow range among subjects in each study group. In the
female groups, phase III migrated distally at a slower speed compared with the male group. In the awake state the respective median PV of 5.5 (2.3-8.7) and 4.3 (2.2-10.0) cm/min in the early-F and mid-L
groups was slower compared with the velocity of 7.7 (3.8-15.0) cm/min of the male group (P = 0.07 and
P < 0.02, respectively; Fig.
4). During sleep, PV of early-F and mid-L
groups were 4.8 (1.6-7.1) and 4.4 (2.3-8.3) cm/min,
respectively, and these values were lower than the 6.3 (2.5-10.0)
cm/min value of the male group (P = 0.08 and
P < 0.04, respectively; Fig. 4). There was no
statistically significant difference between the values of the female
groups and between the values of the awake and asleep states. In
comparison with the MMC cycle length, within-subject variance of PV as
a percentage of the total variance was of a lesser magnitude in all
groups (median 35%, range 21-46%). In the male group variance between subjects was significant (P < 0.002 and
P < 0.001, respectively, for awake and asleep states;
ANOVA).

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Fig. 4.
The propagation velocity of phase III of the migrating
motor complex (MMC) recorded in the early-F and mid-L phases of women
and in men. The data are shown as median values (bars), interquartile
range (boxes), ranges, and outliers ( ). The median
propagation velocities of women were lower compared with those of men
(awake: P = 0.07 and P < 0.02 for
early-F and mid-L phases, respectively; asleep: P = 0.08 and P < 0.04 for early-F and mid-L,
respectively).
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Phase II characteristics.
The mean frequency of contractions was higher in the awake state
compared with sleep [early-F, 2.5 ± 0.8 vs. 1.5 ± 0.8/min (P < 0.01); mid-L, 3.8 ± 1.8 vs. 2.1 ± 1.3/min (P < 0.03); men, 2.9 ± 1.1 vs. 1.8 ± 0.5/min (P < 0.01)]. The mean contraction amplitude was
similar among groups and throughout the study period.
Relative duration of phases I and II
of MMC cycle.
The occupation of different phases of the MMC cycle calculated as a
percentage of the total MMC duration is presented in Table 6. In all study groups, during
wakefulness phase I was shorter and phase II was longer compared with
the values obtained during sleep.
Postprandial motor activity.
Almost all postprandial motor activity occurred while subjects were
awake, and the duration of postprandial motor activity was similar
among groups, although women and men consumed meals of slightly
different caloric content (Table 2). Contraction frequency, amplitude,
and motility index did not reveal differences among groups or between
dinner and lunch.
Clustered contractions.
The frequency of clustered contractions was similar between women and
men during fasting and postprandially. However, in all groups the
postprandial frequency was higher compared with that of the fasting
asleep state (Table 7).
Correlations between ovarian hormones and motility parameters.
In the mid-L phase of the menstrual cycle, propagation velocity of
phase III was positively correlated with serum estradiol concentrations. During wakefulness, the correlation coefficient of this
association was higher (Fig.
5A) than that found for the total study period (r = 0.63, P < 0.05). Also in the mid-L phase, phase III contraction amplitude was
correlated with estradiol concentrations; again, a stronger association
was observed during wakefulness (Fig. 5B) than that for the
total study period (r = 0.69, P < 0.02).

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Fig. 5.
Relationship between serum estradiol concentrations and propagation
velocity (A) and contraction amplitude (B) of
phase III during wakefulness in the mid-L phase in women. Serum
estradiol concentrations were positively correlated with propagation
velocity and contraction amplitude of phase III.
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The MMC cycle duration during sleep in the early-F phase was positively
correlated with serum estradiol concentrations, whereas the same
parameter was negatively correlated with progesterone levels in the
mid-L phase (Fig. 6).

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Fig. 6.
The MMC cycle duration during sleep was positively correlated with
estradiol levels in the early-F phase (A) and negatively
correlated with progesterone levels in the mid-L phase
(B).
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 |
DISCUSSION |
The results of the present study demonstrate that the majority of
the patterns of jejunal motility display similarity between menstruating women and men, although certain aspects of fasting motor
activity are modulated by gender.
The present study has demonstrated for the first time that in
menstruating women, particularly in the mid-L phase, PV of phase III is
slow compared with that observed in men of comparable age. Similar to
the findings of a previous study (15), within-subject variance of propagation was low so that our finding of gender difference is not likely to have resulted by chance. In addition, women
displayed higher phase III contraction amplitude than that of men.
According to our findings, menstrual cycle phase did not appear to be
the major determining factor for the generation of gender difference in
phase III features, because similar findings were observed in women
irrespective of the menstrual phase. Nevertheless, correlations between
estradiol concentrations and PV or contraction amplitude of phase III
were found in the mid-L phase, when circulating levels of female
steroids were relatively high, and not in the early-F phase, when both
steroid levels were low. Thus estradiol may be the gonadal hormone
responsible for the observed gender differences in phase III features.
However, because of the complex effects of these female gonadal
steroids as discussed below and control studies are not available,
these correlations cannot be assumed to be on firm ground.
Central, neurohormonal, or myogenic factors that are peculiar to
females may be operative in the aforementioned gender differences in
jejunal motility. For example, the high contraction amplitude of women
observed during phase III and not at other times may be caused by the
successive lumen-occluding contractions in an intestinal lumen that is
anatomically different from that of men. At the same time, the roles of
ovarian hormones on the motility patterns of women cannot be ignored
for several reasons. First, the fluctuating levels of female steroids
in circulation during the menstrual cycle may not reflect their
long-term effects on tissue receptors, particularly because of their
genomically mediated actions (28). Second, there are data
that demonstrate an influence of female steroids on gastrointestinal
smooth muscle. For example, jejunal electromyographic recordings of
progesterone-treated mammals demonstrate slower distal propagation of
slow waves than that observed in control animals (5),
whereas estrogen treatment enhances in vitro contractility of the
colonic smooth muscle (7). Intestinal transit is slow
during the proestrus-estrus phase of the ovulatory cycle of rats
(24) and during the luteal phase of humans
(29). Furthermore, a mixture of progesterone and estrogen treatment slows gastrointestinal transit (8, 24) and
estrogen treatment delays gastric emptying (8).
Furthermore, the actions of ovarian steroids on a variety of tissues
including neural tissues appear to be nongenomically mediated as well
and include alteration of cell membrane ionic permeability and
regulation of cyclic nucleotide turnover and membrane-bound enzyme
activity (10, 22). For instance, progesterone reversibly
and dose-dependently decreases ionic currents through voltage-sensitive
channels in human intestinal muscle cells in a nongenomic fashion
(3). Therefore, the effects of female gonadal hormones on
jejunal motility may be caused by an interplay of long-term genomic,
short-term nongenomic, and up- or downregulatory effects of these
steroids on their own receptors (28). Together, ovarian
steroids may have a modulatory role in our finding of gender
differences in phase III features. Alternatively, as stated above,
other factors peculiar to females that are yet to be identified may be
also operative.
Similar to previous studies, we have observed that within-subject
variance substantially contributes to the total variance of MMC cycle
duration (15). According to our findings, MMC cycle duration during sleep in the early-F group is longer compared with the
other groups and is positively correlated with estradiol concentrations. On the other hand, MMC cycle length during sleep is
negatively correlated with serum progesterone concentrations in the
mid-L phase. Prolongation of the cycle duration in the early-F phase
may have resulted from estrogen influence because estrogens are the
predominant steroids secreted in this phase, and shortening of the
cycle duration in the mid-L phase may have resulted from progesterone
influence. However, these findings should be interpreted with caution
in light of the high within-subject variance of cycle length, which may
have contributed to our findings.
An unexpected and at the same time interesting finding of the present
study was the prolongation of intercontractile interval of phase III
contractions during sleep. Previous manometric studies, which
investigated wave duration and frequency of phase III contractions, did
not find circadian variation (12, 31, 32). In an
electromyographic study of intestinal slow waves in humans, similar
frequencies were found during wakefulness and deep sleep
(27). Wave duration measurement has inherent technical
difficulties due to the pressure threshold algorithm, and wave duration
is independent of contraction frequency and intercontractile interval
in a waveform. Our finding may be caused by an unknown technical factor
such as sleeving of the intestine over the catheter assembly. However,
to fulfill this condition the sleeving would have to occur only during
wakefulness. Absence of central nervous system arousal during sleep has
been postulated to be responsible for the shortened phase II duration and attenuated phase II contraction frequency (12,
13). The same postulate may be valid for our finding of
prolonged contraction interval of phase III during sleep.
Alternatively, circadian variation may be the inherent character of
neuromuscular tissues, including interstitial cells of Cajal, which
serve as the slow wave pacemaking generators within the
gastrointestinal tract.
Finally, the frequency of clustered contractions was observed to be
similar between women and men. We have also noted that the clustered
contraction frequency is higher during the postprandial period compared
with during fasting while asleep.
Prolonged ambulatory manometry is being used to define motility
patterns that discriminate between disease states and normalcy (13). The present study documented the varying and
unvarying aspects of ambulatory jejunal motility in healthy
menstruating women and men. In addition, we have documented circadian
variation of phase III contraction frequency that did not display
gender difference.
 |
ACKNOWLEDGEMENTS |
The technical assistance of Ayfer Ürün is appreciated.
 |
FOOTNOTES |
This work was supported by a grant from the Turkish Government Planning
Commission (96 K121310).
Address for reprint requests and other correspondence: N. B. Ulusoy, Univ. of Marmara School of Medicine, 81326 Istanbul, Turkey
(E-mail: nefiseulusoy{at}hotmail.com).
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 13 March 2000; accepted in final form 8 August 2000.
 |
REFERENCES |
1.
Baron, TH,
Ramirez B,
and
Richter JE.
Gastrointestinal motility disorders during pregnancy.
Ann Intern Med
118:
366-375,
1993[Abstract/Free Full Text].
2.
Benson, MJ,
Castillo FD,
Wingate DL,
Demetrakopoulos J,
and
Spyrou NM.
The computer as referee in the analysis of human small bowel motility.
Am J Physiol Gastrointest Liver Physiol
264:
G645-G654,
1993[Abstract/Free Full Text].
3.
Bielefeldt, K,
Waite L,
Abboud FM,
and
Conklin JL.
Nongenomic effects of progesterone on human intestinal smooth muscle cells.
Am J Physiol Gastrointest Liver Physiol
271:
G370-G376,
1996[Abstract/Free Full Text].
4.
Bland, JM,
and
Altman DG.
Statistical methods for assessing agreement between two methods of clinical measurements.
Lancet
1:
307-310,
1986[ISI][Medline].
5.
Bortoff, A,
Morello E,
and
Mistretta P.
Effect of progesterone and 17-OH-progesterone on intestinal slow wave propagation.
In: Gastrointestinal Motility, edited by Christensen J.. New York: Raven, 1980, p. 387-393.
6.
Bruce, LA,
Behsudi FM,
and
Danhof IE.
Smooth muscle mechanical response in vitro to bethanecol after progesterone in male rat.
Am J Physiol Endocrinol Metab Gastrointest Physiol
235:
E422-E428,
1978[Abstract/Free Full Text].
7.
Bruce, LA,
and
Behsudi FM.
Increased gastrointestinal motility in vitro following chronic estrogen treatment in male rats.
Proc Soc Exp Biol Med
166:
355-359,
1981.
8.
Chen, TS,
Doong ML,
Chang FY,
Lee SD,
and
Wang PS.
Effects of sex steroid hormones on gastric emptying and gastrointestinal transit in rats.
Am J Physiol Gastrointest Liver Physiol
268:
G171-G176,
1995[Abstract/Free Full Text].
9.
Degen, LP,
and
Phillips SF.
Variability of gastrointestinal transit in healthy women and men.
Gut
39:
299-305,
1996[Abstract].
10.
Farhat, MY,
Abi-Younes S,
and
Ramwell PW.
Non-genomic effects of estrogen and the vessel wall.
Biochem Pharmacol
51:
571-576,
1996[ISI][Medline].
11.
Gill, RC,
Murphy PD,
Hooper HR,
Bowes KL,
and
Kingma YJ.
Effect of the menstrual cycle on gastric emptying.
Digestion
36:
168-174,
1987[ISI][Medline].
12.
Gorard, DA,
Vesselinova-Jenkins CK,
Libby GW,
and
Farthing MJG
Migrating motor complex and sleep in health and irritable bowel syndrome.
Dig Dis Sci
40:
2383-2389,
1995[ISI][Medline].
13.
Husebye, E.
The patterns of small bowel motility: physiology and implications in organic disease and functional disorders.
Neurogastroenterol Motil
11:
141-161,
1999[ISI][Medline].
14.
Husebye, E,
and
Engedal K.
The patterns of motility are maintained in the human small intestine throughout the process of aging.
Scand J Gastroenterol
27:
397-404,
1992[ISI][Medline].
15.
Husebye, E,
Skar V,
Aalen OO,
and
Osnes M.
Digital ambulatory manometry of the small intestine in healthy adults.
Dig Dis Sci
35:
1057-1065,
1990[ISI][Medline].
16.
Hutson, WR,
Roehrkasse RL,
and
Wald A.
Influence of gender and menopause on gastric emptying and motility.
Gastroenterology
96:
11-17,
1989[ISI][Medline].
17.
Kellow, JE,
Borody TJ,
Phillips SF,
Tucker RL,
and
Haddad AC.
Human interdigestive motility: variations in patterns from esophagus to colon.
Gastroenterology
91:
386-395,
1986[ISI][Medline].
18.
Knight, LC,
Parkman HP,
Brown KL,
Miller MA,
Trate DM,
Maurer AH,
and
Fisher RS.
Delayed gastric emptying and decreased antral contractility in normal premenopausal women compared with men.
Am J Gastroenterol
92:
968-975,
1997[ISI][Medline].
19.
Kumar, D.
In vitro inhibitory effect of progesterone on extrauterine human smooth muscle.
Am J Obstet Gynecol
84:
1300-1304,
1962[ISI].
20.
Kumar, D,
Wingate D,
and
Ruckebusch Y.
Circadian variation in the propagation velocity of the migrating motor complex.
Gastroenterology
91:
926-930,
1986[ISI][Medline].
21.
Leon, S,
Glass RH,
and
Kase NG.
Regulation of menstrual cycle.
In: Clinical Gynecologic Endocrinology and Infertility. Baltimore: Williams and Wilkins, 1989, p. 190-193.
22.
McEwen, BS.
Non-genomic and genomic effects of steroids on neural activity.
Trends Pharmacol Sci
12:
141-147,
1991[ISI][Medline].
23.
Parkman, HP,
Wang MB,
and
Ryan JP.
Decreased electromechanical activity of guinea pig circular muscle during pregnancy.
Gastroenterology
105:
1306-1312,
1993[ISI][Medline].
24.
Ryan, JP,
and
Bhojwani A.
Colonic transit in rats: effect of ovariectomy, sex steroid hormones, and pregnancy.
Am J Physiol Gastrointest Liver Physiol
251:
G46-G50,
1986[ISI][Medline].
25.
Schönfeld, J,
Evans DF,
and
Wingate DL.
Daytime and nighttime motor activity of the small bowel after solid meals of different caloric value in humans.
Gut
40:
614-618,
1997[Abstract].
26.
Soffer, EE,
Thongsawat S,
and
Ellerbroek S.
Prolonged ambulatory duodeno-jejunal manometry in humans: normal values and gender effect.
Am J Gastroenterol
93:
1318-1323,
1998[ISI][Medline].
27.
Tassinari, CA,
Coccagna G,
Mantovani M,
Bernardina BD,
Spire JP,
Mancia D,
Vela A,
and
Vallicioni P.
Duodenal EMG activity during sleep.
In: The Nature of Sleep, edited by Jonanovic UD.. Stuttgart, Germany: Fischer, 1973, p. 55-58.
28.
Tsai, MJ,
Clark JH,
Schrader WT,
and
O'Malley BW.
Mechanisms of action of hormones that act as transcription
regulatory factors.
In: Williams' Textbook of Endocrinology, , edited by Wilson JD,
Foster DW,
Kronenberg HM,
and Larsen PR.. Philadelphia: Saunders, 1998, p. 55-94.
29.
Wald, A,
van Thiel DH,
Hoechstetter L,
Gavaler JS,
Egler KM,
Verm R,
Scott L,
and
Lester R.
Gastrointestinal transit: the effect of the menstrual cycle.
Gastroenterology
80:
1497-1500,
1981[ISI][Medline].
30.
Wald, A,
van Thiel DH,
Hoechstetter L,
Gavaler JS,
Egler KM,
Verm R,
Scott L,
and
Lester R.
Effect of pregnancy on gastrointestinal transit.
Dig Dis Sci
27:
1015-1018,
1982[ISI][Medline].
31.
Wilmer, A,
Andrioli A,
Coremans G,
Tack J,
and
Janssens J.
Ambulatory small intestinal manometry. Detailed comparison of duodenal and jejunal motor activity in healthy man.
Dig Dis Sci
42:
1618-1627,
1997[ISI][Medline].
32.
Wilson, P,
Perdikis G,
Hinder RA,
Redmond EJ,
Anselmino M,
and
Quigley EMM
Prolonged ambulatory antroduodenal manometry in humans.
Am J Gastroenterol
89:
1489-1495,
1994[ISI][Medline].
Am J Physiol Gastrointest Liver Physiol 280(2):G255-G263
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