Effect of gender on the development of hypocapnic
apnea/hypopnea during NREM sleep
X. S. ZHOU, S. SHAHABUDDIN, B. R. ZAHN, M. A. BABCOCK, AND M. S. BADR
John D. Dingell Veterans Affairs Medical Center, and Division of Pulmonary and Critical Care
Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201
Received 15 March 1999; accepted in final form 14 February 2000
Zhou, X. S., S. Shahabuddin, B. R. Zahn, M. A. Bab-
cock, and M. S. Badr. Effect of gender on the development
of hypocapnic apnea/hypopnea during NREM sleep. J Appl
Physiol 89: 192–199, 2000.—We hypothesized that a de-
creased susceptibility to the development of hypocapnic cen-
tral apnea during non-rapid eye movement (NREM) sleep in
women compared with men could be an explanation for the
gender difference in the sleep apnea/hypopnea syndrome. We
studied eight men (age 25–35 yr) and eight women in the
midluteal phase of the menstrual cycle (age 21–43 yr); we
repeated studies in six women during the midfollicular
phase. Hypocapnia was induced via nasal mechanical venti-
lation for 3 min, with respiratory frequency matched to
eupneic frequency. Tidal volume (VT) was increased between
110 and 200% of eupneic control. Cessation of mechanical
ventilation resulted in hypocapnic central apnea or hypo-
pnea, depending on the magnitude of hypocapnia. Nadir
minute ventilation in the recovery period was plotted against
the change in end-tidal PCO2(PETCO2) per trial; minute ven-
tilation was given a value of 0 during central apnea. The
apneic threshold was defined as the x-intercept of the linear
regression line. In women, induction of a central apnea re-
quired an increase in VT to 155 ? 29% (mean ? SD) and a
reduction of PETCO2by ?4.72 ? 0.57 Torr. In men, induction
of a central apnea required an increase in VT to 142 ? 13%
and a reduction of PETCO2by ?3.54 ? 0.31 Torr (P ? 0.002).
There was no difference in the apneic threshold between the
follicular and the luteal phase in women. Premenopausal
women are less susceptible to hypocapnic disfacilitation dur-
ing NREM sleep than men. This effect was not explained by
progesterone. Preservation of ventilatory motor output dur-
ing hypocapnia may explain the gender difference in sleep
apneic threshold; control of breathing; central apnea; hypo-
capnia; ventilation; mechanical; follicular; luteal; progester-
SLEEP APNEA/HYPOPNEA SYNDROME is more prevalent in
men than in women (29). Differences in upper airway
structure/function and/or ventilatory control during
sleep could explain the gender difference. The relative
contribution of each mechanism is uncertain.
The differences in upper airway structure between
genders have clearly been shown during wakefulness,
inasmuch as men have larger pharynges and tracheae
(4, 26). Likewise, upper airway resistance (Rua) is
higher in men than in women, and upper airway dilat-
ing muscle response to negative pressure is reduced in
men relative to women (16a). However, no gender com-
parison has been done during sleep. Furthermore, the
difference in upper airway structure does not account
for the reported difference in the prevalence of central
sleep apnea (see below).
Gender differences in ventilatory control have also
been documented during wakefulness, including in-
creased sensitivity to CO2in men relative to women (1,
8, 26, 27). Likewise, the higher prevalence of central
sleep apnea in men than in women suggests a gender
difference in CO2chemosensitivity and/or higher pro-
pensity to sleep discontinuity (29). Thus the precise
mechanism(s) underlying gender differences in the oc-
currence of sleep apnea remains uncertain.
In a previous study investigating the effect of in-
duced central apnea on upper airway patency, we ex-
perienced substantial difficulty inducing central ap-
hypothesized that women are less susceptible to the
development of hypocapnic central apnea. Therefore,
we used nasal mechanical ventilation (MV) to compare
the differences in apneic threshold between men and
The experimental protocol was approved by the Human
Investigation Committee of the Wayne State University
School of Medicine and the Detroit Veterans Affairs Medical
Center. Informed written consent was obtained from all sub-
jects. We studied eight men (age 29 ? 2 yr) and eight women
in the midluteal phase of the menstrual cycle (age 32 ? 3 yr)
(Table 1). An additional study was performed on six of the
women during the midfollicular phase of the menstrual cycle
(Table 2). All subjects were healthy nonsnorers and were not
receiving any medication; none of the women were taking
birth control drugs. Studies during the luteal phase were
conducted between days 17 and 21 of the menstrual cycle,
and studies during the follicular phase were conducted be-
tween cycle days 6 and 11 (with day 1 being the 1st day of
menses). Menstrual cycle phase was confirmed by progester-
one assay (follicular phase ?1.5 ng/ml; luteal phase ?2.5
Address for reprint requests and other correspondence: M. S. Badr,
Rm. 3923, 3-Hudson, Harper Hospital, 3990 John R, Detroit, MI
48201 (E-mail: firstname.lastname@example.org).
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.
J Appl Physiol
89: 192–199, 2000.
ng/ml). Subjects were instructed to restrict their sleep on the
night before the study (total sleep time 4–6 h). The study was
done during regular sleep hours.
Measurements. An appropriate-sized tight-fitting nasal
continuous positive airway pressure mask (Respironics, Mur-
rysville, PA) was glued to the face with liquid latex to prevent
mask leaks and was connected to the ventilation circuit. Tape
was placed over the mouth to restrict subjects to nasal
breathing. Airflow was measured by heated pneumotachom-
eter (model 3710, Hans Rudolph, Kansas City, MO) con-
nected to the mask. Tidal volume (VT) was obtained by
integrating the pneumotachograph flow signal (model FV-
156 Integrator, Validyne, Northridge, CA). Respiration was
also monitored using inductance plethysmography to mea-
sure ribcage and abdominal respiratory efforts (Respitrace,
Ambulatory Monitoring). This was used as a redundant mea-
surement of ventilation and timing. Inspiratory muscle ac-
tivity was obtained by surface electromyogram (EMG) elec-
trodes (Medi-Trace, Buffalo, NY) placed 2–4 cm above the
right costal margin in the anterior axillary line. End-tidal
AEI Technologies, Pittsburgh, PA).
To confirm the central etiology of apnea and to ascertain
upper airway mechanics, supraglottic pressure was mea-
sured with a solid-state catheter (model MPC-500, Millar
Instruments, Houston, TX). A 10% lidocaine spray was used
to provide topical anesthesia to one nostril and the pharynx
before catheter insertion. The catheter was threaded through
a hole in the nasal mask, through the nose, and positioned in
the hypopharynx just below the base of the tongue, as deter-
mined by visual inspection of the tip. Airflow, measured by
the pneumotachometer through the nasal mask, and supra-
glottic pressure, measured with the catheter, were recorded
using Biobench data acquisition software (National Instru-
ments, Austin, TX) on a separate computer. Pressure-flow
loops were used to confirm the absence of inspiratory flow
limitation (22). Rua was determined from the linear portion
of the inspiratory arm of the pressure-flow loops. Rua
throughout inspiration was determined from the slope of the
pressure-flow curve and expressed in centimeters H2O per
liter times seconds. Satisfactory pressure-flow loops were
obtained in 12 subjects (6 men and 6 women). Control Rua
was calculated for the five control breaths before MV. The
nadir breath for hypopnea trials was selected as a represen-
tative “low-drive” recovery breath.
Electroencephalograms, electrooculograms, and chin EMG
were attached using the international 10–20 system of elec-
trode placement (electroencephalogram: C3-A2, C4-A1, Oz-
A2; electrooculogram: F7-A2 and F8-A1). Data were logged
onto a polygraph recorder (model 78, Grass, West Warwick,
RI), and sleep stage was scored according to standard meth-
MV protocol. Hyperventilation was achieved using a pres-
sure support ventilator (Quantum PSV, Healthdyne Technol-
ogies, Marietta, GA). The nasal mask dead space was deter-
mined to be 110.5 ? 1.5 ml. Accumulation of CO2in the
circuit was prevented by the biased flow provided by the
ventilator and from an expiratory mushroom valve in-line
between the pneumotachometer and the ventilator tubing.
No rebreathing of CO2took place, as shown by PCO2at the
start of inspiration equivalent to room air values. During the
control and recovery periods, the ventilator was set at an
expiratory positive airway pressure (EPAP) of 2.0 cmH2O.
This was the minimum EPAP allowed by the device. During
periods of hyperventilation, the ventilator was set in sponta-
neous timed mode, with timing matched to each subject’s
Table 1. Physical characteristics of the male and
Subject Age, yr Ht, cmWt, kg BMI, kg/m2
BMI, body mass index.
Table 2. Comparison of the PETCO2and progesterone levels during the luteal and follicular phases of the
WakefulnessNREM sleepAP, mmHgProgesterone, ng/ml
PETCO2, end-tidal PCO2; AP, apneic threshold; NREM, non-rapid eye movement; Lu, luteal; Fol, follicular.
GENDER EFFECTS ON HYPOCAPNIC APNEA/HYPOPNEA
eupneic rate. Hyperventilation was achieved by increasing
the inspiratory pressure of the ventilator during expiration.
The inspiratory pressure was increased by 1.0 cmH2O from
an initial level of 2.0 cmH2O each successive trial, which
resulted in increased VT (range 110–230% of eupneic con-
trol). Spontaneous respiratory effort remained in most trials,
as evidenced by persistence of an initial negative deflection of
supraglottic pressure signal and persistent, albeit reduced,
diaphragmatic EMG activity. MV was continued for 3 min
and was terminated during expiration, to an EPAP of 2.0
cmH2O. The post-MV period, or recovery period, was ob-
served for posthyperventilatory inhibition. The ensuing hy-
pocapnia resulted in hypopnea or central apnea, depending
on the magnitude of hypocapnia. Apnea was defined as a
period of no airflow for ?5.0 s. Stable NREM sleep in stage 2
or slow-wave sleep was selected for each trial. Each trial was
repeated twice, and trials were selected for analysis only if
the sleep state remained stable throughout the trial, includ-
ing the recovery. Trials were separated by ?3 min.
Data analysis. We analyzed only trials with stable sleep
state, as evidenced by the absence of arousal (20) or ascent to
a lighter sleep state. PETCO2was averaged over 10 breaths
during wakefulness at the beginning of the study. For each
trial, the control period was represented by the average of
five breaths immediately preceding the onset of MV. The
hyperventilation data were the calculated averages of the
last five mechanically ventilated breaths before the ventila-
tor was turned back to an EPAP of 2.0 cmH2O. The change in
PETCO2was calculated as the difference between the con-
trol period and the last five MV breaths. For trials with
hypopnea, the minute ventilation (V˙E) reported was from the
first breath in the recovery period. This represented the
nadir breath, which was defined as the breath with the
lowest V˙E after cessation of MV. The nadir breath occurred
on the first recovery breath in the majority of trials and
within the first three breaths in all trials. V˙E was given a
value of 0 during central apnea, and the apnea length was set
?5.0 s. The changes in V˙E were plotted against the changes
in PETCO2for each trial. In addition, apnea length was mea-
sured and plotted vs. the corresponding change in PETCO2
for each apnea trial.
Statistical analysis. Linear regression analysis was per-
formed on the change in V˙E and the change in PETCO2
to determine the PETCO2threshold associated with zero
V˙E (apnea). Thus the predicted apneic threshold was defined
as the x-intercept of the linear regression line. Unpaired
Student’s t-tests were performed to compare the men and
women (luteal phase). Paired Student’s t-tests were used to
compare the six women during the luteal and follicular
phases. One-way repeated-measures ANOVA was used to
compare the actual change in PETCO2measured from the
first apnea and the calculated change in PETCO2at the apneic
threshold. Statistical analysis was performed with Sigma-
Stat 2.0 (Jandel Scientific, San Rafael, CA). P ? 0.05 was
chosen as the accepted level of significance.
A representative polygraph record of one hypopneic
trial is shown in Fig. 1. MV was initiated during
expiration in stable NREM sleep. Ventilator frequency
was matched to the subject’s spontaneous eupneic
breathing. VT increased to 125% of control and resulted
in a mild hypocapnia (?PETCO2? ?2.2 Torr from con-
trol). Note the persistence of spontaneous inspiratory
effort during MV, as evidenced by initial negative de-
flection on mask pressure signal and persistence of
inspiratory EMG activity. Cessation of MV resulted in
a decreased VT (55% of control), with no corresponding
change in breathing frequency. Figure 2 shows a rep-
resentative polygraph record of one trial in which a
central apnea resulted when the MV was terminated.
In this trial, during MV, the VT was increased 180%
Fig. 1. Polygraph record of a trial that
resulted in hypopnea after 3 min of
mechanical ventilation. Transitions of
eupneic breathing to mechanical hy-
perventilation are shown, along with
the point where mechanical ventilation
was terminated. Note the decrease in
flow, inspired volume, and mask pres-
sure during the hypopneic period. EMG,
electromyogram; PETCO2, end-tidal PCO2.
GENDER EFFECTS ON HYPOCAPNIC APNEA/HYPOPNEA
over control, and the PETCO2was decreased ?6.23 Torr
below control. After the MV was removed, the flow and
VT fell to zero. Also, there was no negative deflection on
the supraglottic pressure recording (not shown), and
there was no inspiratory EMG activity, also suggesting
no effort to breathe (central apnea).
For the men, a total of 125 trials were recorded: 88
produced hypopneas, and 37 were apneic trials. Among
the women (luteal phase), there were 134 successful
trials: 106 produced hypopnea, and 28 were apneic
trials. To induce apnea in the men, the VT was in-
creased 142 ? 13% above eupneic control, and the
subsequent apnea length was 24.8 ? 9.4 s (range
5.4–47.0 s). In women, the VT was increased 155 ? 29%
(luteal phase) above eupneic control to produce an
apnea; the subsequent apnea length was 20.8 ? 8.3 s
(range 8.8–46.8 s). No differences were found between
the two groups with regard to PETCO2during wakeful-
ness (44.5 ? 0.3 and 45.3 ? 0.5 Torr for men and women,
respectively) and PETCO2during the NREM control period
(47.9 ? 0.6 and 48.8 ? 0.5 Torr for men and women,
Representative plots of the data [V˙E (percentage
of control) vs. change in PETCO2] from the hypopneic
and the apneic trials are shown for one man (Fig. 3A)
and one woman (Fig. 3B). The linear regression line
was fitted to the data from the hypopneic trials only,
and the equation of the linear regression line was used
to calculate the apneic threshold. The man differed
old, and the apneic threshold from the first apneic trial.
The predicted apneic threshold was very close to the
apneic threshold measured for the first apneic trial; this
was also true for the group (see below).
The mean group data for men and women for the
calculated apneic threshold and the apneic threshold
measured for the first apneic trial are shown in Fig. 4.
There was a significant difference between the men
and the women for the calculated apneic threshold
(P ? 0.004) and for the measured apneic threshold (P ?
0.001). No difference was found between the calculated
and the measured apneic threshold within each group.
The slopes of the linear regression equations were
substantially different (P ? 0.006) between the men
and the women (Fig. 4A), which indicates higher che-
moresponsiveness in the men than in the women.
To determine whether ventilatory changes were due
to changes in Rua, the Rua was measured from the
linear portion of the pressure-flow curve for the men
and the women (n ? 6 in each group; Fig. 5). Rua
during the control period was not different between
men and women (8.8 ? 1.1 and 8.5 ? 1.5 cmH2O ? l?1? s
for men and women, respectively), nor was Rua differ-
ent after MV (8.5 ? 1.5 and 9.0 ? 2.1 cmH2O ? l?1? s for
men and women, respectively). Thus reduced ventila-
tory output was not associated with changes in Rua in
men and women.
Six of the women were studied again during the
follicular phase to ascertain whether the phase of the
menstrual cycle influenced the apneic threshold.
Eighty-seven trials were conducted (64 resulted in hy-
popnea and 23 in apnea) in the six women during the
follicular phase tests. Achievement of central apnea
during the follicular phase required an increase in VT
Fig. 2. Polygraph record of a trial that resulted in an apnea after 3 min of mechanical ventilation. We would
classify this trial as a central apnea, as evidenced by the lack of effort in the EMG signal.
GENDER EFFECTS ON HYPOCAPNIC APNEA/HYPOPNEA
to 165 ? 37% of control and a reduction of PETCO2by
?4.9 ? 0.3 Torr. Comparison of the subset of women
studied at the two phases of the menstrual cycle re-
vealed no difference in the calculated or the measured
apneic threshold (Fig. 6, B and C). In addition, there
was no difference in chemoresponsiveness, as shown by
the change in ventilation relative to the change in
PETCO2between the luteal and the follicular phases
The purpose of this study was to examine whether
there was a gender difference in the susceptibility to
hypocapnic apnea/hypopnea during sleep. Our data
showed that the change in PETCO2necessary to cause a
central apnea was significantly different between men
and women. This difference may not be due to proges-
terone, inasmuch as no difference in the change in
PETCO2at the apneic threshold was found in the six
women studied during the luteal and follicular phases
of the menstrual cycle.
Fig. 3. Data from individual men (A) and women (B)
used to determine each subject’s apneic threshold.
Lines, linear regression lines used to fit the data
from the hypopneic trials. The equation of the line
was used to calculate the change in PETCO2, where
minute ventilation (V˙E) would equal zero, and this
was called the apneic threshold.
Fig. 4. Comparison of the slope of the regression line (A), the pre-
dicted apneic threshold (B), and the measured change in PETCO2
from the first apneic trial (C) in men and women. The slope and
predicted and actual values were significantly different between the
two groups (?P ? 0.001; *P ? 0.004;#P ? 0.001). Within each group,
no differences were found with regard to the predicted apneic thresh-
old value and the value measured from the first apneic trial. Values
are means ? SE.
Fig. 5. Upper airway resistance measured during the control period
and for the nadir hypopneic breath after cessation of mechanical
ventilation for men and women. No differences were noted in upper
airway resistance in either group before or after mechanical hyper-
ventilation. Values are means ? SE.
GENDER EFFECTS ON HYPOCAPNIC APNEA/HYPOPNEA
This gender comparison allows us to propose that
healthy young women are less susceptible than men to
hypocapnic central apnea during NREM sleep. How-
ever, our sample size is relatively small, owing to the
difficulty in conducting interventional studies in
heavily instrumented subjects. Therefore, caution is
mandated in interpreting our findings, inasmuch as
our data may not be representative of a large cross-
sectional study’s reflection of the whole population.
Role of gender in the development of hypocapnic
apnea/hypopnea. We considered several explanations
for the difference in the occurrence and magnitude of
posthyperventilation inhibition of ventilatory motor
output, including differences in upper airway caliber,
metabolic rate, and chemoresponsiveness.
The gender difference in apneic threshold cannot be
explained by a difference in upper airway mechanics or
baseline PETCO2. Although a patent upper airway may
facilitate the development of arterial and, hence, med-
ullary hypocapnia, we included only nonsnorers with-
out evidence of significant sleep-induced upper airway
narrowing. This was evidenced by the absence of snor-
ing and the absence of inspiratory flow limitation on
pressure-flow loops (n ? 12) (22). Likewise, our find-
ings could not be explained by differences in metabolic
rate. Although data are limited, the available studies
demonstrate no difference in metabolic rate between
women and men during sleep (6, 28). Furthermore, it is
unlikely that MV per se would decrease metabolic rate
preferentially in one gender.
The gender difference in hypocapnic response indi-
cates a difference in chemoresponsiveness, at least in
the hypocapnic range. Our findings are in contrast to
previous studies showing no gender difference in the
hypercapnic ventilatory response during NREM sleep
(25). Women have been shown to have lower hypoxic
and hypercapnic ventilatory responses than men dur-
ing wakefulness but not during NREM sleep (1, 25, 26).
Whether the response to hypocapnia during NREM
sleep is different between men and women is unknown.
Similarly, whether the difference is unique to the CO2
stimulus or whether it encompasses other stimuli (i.e.,
hypoxia) remains to be determined.
We were intrigued by the apparent difference in
chemoresponsiveness between our study and previous
studies in awake subjects. Unfortunately, studies on
chemoresponsiveness are difficult to interpret, inas-
much as sleep per se has a variable effect on airway
resistance, which could reduce the response to any
stimulus. In addition, Rua is affected by changes in
ventilatory motor output (2). Therefore, the ventilatory
response to CO2depends on the level of CO2, the
baseline Rua, and its response to chemoreceptor stim-
uli. It is possible that previous studies included men
with high Rua. The higher Rua in men than in women
may have dampened the ventilatory response to hyper-
capnia, masking a higher CO2chemoresponsiveness in
men. In contrast, all our subjects were nonsnorers with
normal upper airway mechanics.
Mechanism(s) of gender-related differences in chemo-
responsiveness. We considered several possibilities to
explain the gender difference in chemoresponsiveness.
Specifically, we considered 1) the putative protective
role of progesterone and/or estrogen vs. 2) the destabi-
lizing role of testosterone. Progesterone is a known
ventilatory stimulant that leads to increased ventila-
tion in humans (8, 27) and is presumed to protect
premenopausal women from sleep-disordered breath-
ing. The ventilatory effects of progesterone are more
pronounced during the luteal than during the follicular
phase of the menstrual cycle (27). In contrast, estrogen,
by itself, has been shown not to affect ventilation (8)
but, in combination with progesterone, will elevate
ventilation (8, 18). However, the lack of difference
between the follicular and luteal phases argues against
progesterone alone or a progesterone-estrogen combi-
nation as underlying factors minimizing the propensity
for the development of central apnea.
Although gender difference in ventilatory control has
been attributed to female hormones, testosterone is
also known to influence ventilation (21, 27). There is
substantial evidence implicating testosterone as a de-
stabilizer of respiration in sleeping humans (11, 13,
19). For example, testosterone administration to hy-
pogonadal men results in increased hypoxic ventilatory
response during wakefulness and an increased fre-
quency of apnea and hypopnea during sleep (27). In a
Fig. 6. A comparison of the slope of the regression line (A), the
calculated change in PETCO2at the apnea threshold (B), and the
actual PETCO2at the first apnea (C) for women (n ? 6) studied during
the luteal and follicular phases of the menstrual cycle. There were
no differences between the phases. Values are means ? SE.
GENDER EFFECTS ON HYPOCAPNIC APNEA/HYPOPNEA
group of seven obese men, six exhibited episodes of
desaturation and disordered breathing and one was
hypogonadal and did not experience any desaturations
or disordered breathing (9). Several case studies have
shown the development of upper airway obstruction
after testosterone administration (11). The available
data, taken together, support our interpretation that
the gender difference in the apneic threshold was due
to testosterone effect. This interpretation remains
speculative in the absence of studies directly investi-
gating the ventilatory effects of testosterone during
Implications for sleep apnea. The noted difference in
the apneic threshold between men and women sug-
gests that women are less susceptible to the develop-
ment of central apnea. Evidence in the literature sug-
gests a male propensity for the development of central
sleep apnea. For example, Franklin et al. (7) studied 20
consecutive patients with central sleep apnea, and only
1 was a woman. In another study of 327 screened
patients, 14 patients were selected because they met
the criteria of central apnea index ?5 or apnea-hypo-
pnea index ?10; only 1 of these 14 subjects was a
woman (5). Thus central apnea appears to be more
prevalent in men.
The gender difference in the susceptibility to hypo-
capnic inhibition may also influence the development
of obstructive sleep apnea. We and others have shown
that individuals with a collapsible upper airway during
sleep and with evidence of inspiratory flow limitation
are dependent on the ventilatory motor output to pre-
serve upper airway patency (2, 10, 16, 27). For exam-
ple, mild hypocapnic hypopnea was associated with
increased Rua or worsening inspiratory flow limitation
only in snoring subjects who demonstrated inspiratory
flow limitation during eupnea (2). Thus hypocapnia
may cause a significant reduction in ventilatory motor
output and subsequent upper airway narrowing in a
snoring man but less ventilatory inhibition and, hence,
less upper airway compromise in a woman with similar
snoring and baseline upper airway mechanics.
Central apnea rarely occurs as a single event. In-
stead, several factors conspire to perpetuate breathing
instability during sleep after central apnea. First,
when the ventilatory motor output totally ceases dur-
ing apnea, the inertia of the ventilatory control system
will prevent the resumption of rhythmic breathing
until the arterial PCO2increases 4–6 Torr above eu-
pnea (12). Second, central apnea results in pharyngeal
airway narrowing or occlusion (3). Third, resumption of
breathing requires opening an occluded airway, over-
coming tissue adhesion force (15) and craniofacial
gravitational forces. Finally, the prolongation of apnea
leads to variable asphyxia (hypoxia and hypercapnia)
and transient arousals, resulting in ventilatory over-
shoot, subsequent hypocapnia, and further apnea/hy-
popnea. The aforementioned sequence is corroborated
by a recent epidemiological study showing that apneas
are followed by a larger ventilatory overshoot (14) and
a more pronounced pressor response than hypopneas.
Accordingly, the occurrence of a hypopnea, rather than
apnea, in women may mitigate the ensuing gas ex-
change and the acute pressor response and perhaps
decrease the likelihood of sustained instability. This
may contribute to the difference between men and
women in the prevalence of sleep-disordered breath-
ing. The clinical significance of this postulated differ-
ence has yet to be determined.
In summary, the gender difference in response to
hypocapnia indicates that men are more susceptible to
ventilatory inhibition on withdrawal of chemical stim-
uli. This may contribute (at least partly) to the differ-
ence in the prevalence of sleep apnea/hypopnea be-
tween men and women.
We thank A. T. Taylor for help with data analysis and Dr. James
Rowley for critical review of the manuscript.
This work was supported by the Veterans Affairs Medical Service
and the National Heart, Lung, and Blood Institute. M. S. Badr is a
Career Investigator of the American Lung Association.
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