INTRODUCTION

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VENTILATORY RESPONSES TO ENVIRONMENTAL hypoxia have been the subject of a great amount of scientific inquiry over the last 100 yr. Humans compensate for the decreased inspired PO₂ of high altitude by a progressive, time-dependent increase in ventilation, termed ventilatory acclimatization (5). After rapid ascent to 4,300 m elevation, ventilation increases progressively during the first 6-8 days (30). An increase in carotid body sensitivity to hypoxia occurs with acclimatization and likely plays a key role in the acclimatization process (18, 40).

Relative to the number of studies on men, few studies have specifically examined ventilatory adaptations to high altitude in women. Women living at low altitude or acclimatized to high altitudes have greater ventilation relative to carbon dioxide production [lower end-tidal PCO₂ (PET_CO2)] compared with men (1, 8, 13, 17, 42). This greater effective ventilation in women compared with men is even present in the follicular phase of the menstrual cycle when ovarian hormone levels are low (1). Furthermore, in normally menstruating women at low altitudes, resting ventilation is elevated in the midluteal phase compared with the follicular phase (3, 9-12, 19, 20, 23, 31, 34-37, 42, 44). Progesterone is primarily responsible for increasing ventilation in the luteal phase, although estradiol potentiates the ventilatory effects of progesterone (7, 31, 32, 38). The ovarian hormones increase ventilation by acting on receptor-mediated mechanisms at both central and peripheral sites (2, 7, 15, 32, 39). Progesterone increases carotid body sensitivity, and estradiol raises central nervous system translation of the carotid body signal into increased ventilation (15, 16). Furthermore, estradiol is also needed to induce progesterone receptors (7).

In women, however, menstrual cycle phase effects on hypoxic and hypercapnic ventilatory chemosensitivity are difficult to demonstrate. In eumenorrheic women, the hypoxic ventilatory response (HVR) was increased during the luteal compared with the follicular phase in three studies (34, 35, 42) but was unchanged in three other studies (3, 9, 31). Similarly, in 11 studies that made repeated measures of the hypercapnic ventilatory response (HCVR) throughout the menstrual cycle, six studies (9-11, 20, 34, 44) reported an increase in the slope of the HCVR in the luteal compared with the follicular phase, whereas five studies (3, 31, 36, 37, 42) found no change. The inconsistency of findings does not appear to be related to the methods used to assess the HVR or HCVR or to the frequency at which these measures were made throughout the menstrual cycle. The absence of a clear increase in HVR and HCVR in the luteal phase of the menstrual cycle may be affected by the wide range of endogenous ovarian hormone levels common in the luteal phase (21) and the considerable inherent variability in these measures of ventilatory drive (33). In contrast, in women, the effect of ovarian hormones on the HVR is obvious when endogenous levels are high, as in pregnancy (24, 25), or absent after ovariectomy (32).

Gender may also influence the rate and magnitude of ventilatory acclimatization (1, 8, 13, 17, 42). Hannon (17) studied unacclimatized women lowlanders during their first 2 wk at 4,300 m and concluded that they achieved ventilatory acclimatization more rapidly than men did. This finding suggests that women may be predisposed to a more rapid ventilatory acclimatization response by virtue of their higher effective ventilation.

To our knowledge, no previous studies of female lowlanders have examined the influence of ovarian hormones on ventilatory acclimatization at high altitude. The presence of a ventilatory effect at sea level and the finding of increased ventilation compared with men suggest that there is the potential for the female ovarian hormones to modulate ventilatory acclimatization to high altitude. Therefore, we hypothesized that ventilatory acclimatization to high altitude would occur more quickly and to a greater degree in female lowlanders in their early-to-midluteal phase compared with female lowlanders in their follicular menstrual cycle phase, because of the ventilatory and stimulatory effects of the ovarian hormones in the luteal phase. Second, we hypothesized that, compared with male lowlanders at the same altitude, women would have higher resting effective ventilation and accelerated ventilatory acclimatization. To test these hypotheses, indexes of ventilatory acclimatization (resting ventilatory parameters and ventilatory chemosensitivity) were measured at sea level and throughout a 12-day residence at 4,300-m altitude in women either in their follicular or luteal phase of the menstrual cycle. To test possible gender effects, data on men were obtained from previously published studies at the same altitude (14, 27, 30).

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subjects. Twenty-seven women volunteers participated in this study. Twenty-two subjects completed the ventilatory protocols at sea level and high altitude and had corresponding ovarian steroid hormone profiles and menstrual cycle histories that substantiated their normal menstrual cycle status. The subjects were nonsmoking, eumenorrheic, sea-level residents of average fitness. No volunteer had altitude exposure >1,500 m within the 6 mo before the study. The 22 women completing the study had a mean age of 22.5 ± 0.8 (SE) yr, weight of 65.6 ± 2.4 kg, height of 166.1 ± 1.2 cm, and a peak O₂ uptake (O₂) (cycle ergometry) of 39.5 ± 1.7 ml · kg¹ · min¹. All subjects read and signed an informed consent approved by the Human Subjects Committees from the University of Colorado Health Sciences Center, Stanford University, and the US Army Surgeon General's Human Use Review Committee.

Study design. This study used a between-group (follicular vs. luteal) with repeated-measures, within-group (sea level and 4,300 m) design in which the resting ventilation and ventilatory chemosensitivity of unacclimatized women were measured during either the follicular or luteal phase of their menstrual cycle at sea level and again at 4,300-m altitude. Because of logistical constraints, the study was conducted during the spring and summer of 1996 and 1998. In 1996, attempts were made to study 19 subjects at sea level in both their follicular and luteal phases. The sea-level experiments were conducted during two identical 12-day test periods separated by 1-8 wk, depending on personal schedule requirements. Volunteers were then divided into two groups, with one-half assigned to arrive at high altitude at the beginning of their follicular phase and the other group to arrive at the beginning of their luteal phase (see Menstrual cycle documentation). In 1998, eight subjects were studied during a single 12-day test period at sea level. In addition, because of difficulties in scheduling tests to coincide with the onset of the follicular and luteal phases, these subjects entered testing without specific regard to the status of their menstrual cycle phase. After sea-level testing was completed, analyses of serum progesterone and estradiol concentrations were used to confirm the menstrual cycle phase in which testing was performed. Attempts were then made to schedule subjects to commence their high-altitude tests in the same menstrual cycle phase in which they completed their sea-level testing. The same protocols, study personnel, and equipment were used during the 12-day test periods in 1996 and 1998.

Menstrual cycle documentation. A minimum of a 3-mo menstrual cycle history was documented by diary or by information provided by the subject before the start of testing. Each subject kept a menstrual cycle diary noting the dates of her menses, the duration of her menstrual cycle, and the day of detection of luteinizing hormone in her urine (OvuQuick ovulation prediction kit, Becton-Dickson, Rutherford, NJ). The follicular phase was defined as beginning with the first day of menses and lasting until detection of ovulation, at which time the luteal phase began. At sea level and high altitude, day 1 of a study period was the day after menses began or detection of ovulation. Blood samples for analysis of ovarian steroid hormones were obtained by venipuncture at sea level and high altitude on days 1, 3, 6, 9, 10, and 12. After all testing was completed, progesterone and estradiol serum concentrations were determined by RIA (Diagnostic Products Coat-A-Count kit) and/or chemiluminescent enzyme immunoassay (Diagnostic Products Immulite kits) and used in conjunction with each subject's menstrual cycle diary to finalize menstrual cycle phase assignments. Women whose cycles were abnormal (hormone levels below detectable limits or consistently low) were classified as being in the follicular phase for the purpose of analyses, because low estradiol and progesterone concentrations are characteristics of the early follicular phase. Poststudy analysis of plasma progesterone and estradiol, along with menstrual cycle histories, revealed that 8 women were in their luteal phase and 14 were in their follicular phase on arrival and during the first 3-7 days at 4,300 m. Each of these subjects had sea-level studies in the corresponding cycle phase.

Ventilatory studies. At both sea level and high altitude, ventilatory studies were normally performed before breakfast and always more than 2 h after a meal. At sea level, resting ventilation and ventilatory chemosensitivity studies (isocapnic HVR and HCVR) were measured on days 1 or 2 and 7 or 8 of each sea-level 12-day test period. Sea-level ventilatory studies were usually performed in the morning. At high altitude, resting ventilation studies were performed the afternoon of day 1 (2-3 h after arrival) and on the mornings of days 2, 3, 5, 7, and 12. The ventilatory chemosensitivity studies were conducted on the mornings of days 2, 7, and 12.

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Arterial blood gases. In the first year of this study, on day 10 at sea level and high altitude, resting arterial samples were drawn anaerobically from an indwelling radial artery catheter ~90 min after catheter insertion. Subjects were seated in a semirecumbent posture for ~60 min before the samples were collected. The samples were immediately placed on ice and analyzed within 30 min for arterial PO₂ (Pa_O2), PCO₂ (Pa_CO2), and pH (pH_a) (ABL 300, Radiometer, Copenhagen, Denmark).

Statistical analysis. Differences between menstrual cycle phases were compared by a two-factor ANOVA (menstrual cycle phase and time at altitude) with repeated measures in one factor (time at altitude). Tukey post hoc comparisons were used to identify significant differences among means. Differences between menstrual cycle phases within a subject at sea level were compared with a paired t-test. Tests for possible relationships between each subject's resting ventilatory parameters and ovarian hormone concentrations were performed using the Pearson product-moment correlation method. All statistical analyses were performed by using Sigma Stat version 2.03 (SPSS). Data are expressed as means ± SE. Significant differences are presented with its 95% CI.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Comparison between menstrual cycle phases. During the first 7 days of altitude exposure, 19 subjects remained within the same phase of their menstrual cycle in which they had arrived. Between days 4 and 7, two subjects in the follicular phase and one subject in the luteal phase transitioned to the other phase of their menstrual cycle (see Menstrual cycle documentation). Therefore, because of the decreasing number of subjects remaining within their respective menstrual cycle phase with time at 4,300 m, analysis of the possible effects of menstrual cycle phase on ventilatory acclimatization to altitude was limited to the first 7 days at high altitude and the corresponding menstrual cycle phase tests at sea level. As shown in Table 1, resting O₂, Sa_O2, and E or PET_CO2, as an index of effective alveolar ventilation, were similar in the follicular- and luteal-phase groups at sea level and during the first 7 days at high altitude. The time course for the development of ventilatory acclimatization, expressed as the rate of decline in PET_CO2 per day (PET_CO2/day) relative to mean sea-level values, was not significantly different between menstrual cycle phases during the first 2 days (follicular: 3.6 ± 0.4 Torr PET_CO2/day; luteal: 3.2 ± 0.5 Torr PET_CO2/day) or 6 days (follicular: 1.5 ± 0.1 Torr PET_CO2/day; luteal: 1.4 ± 0.1 Torr PET_CO2/day) at high altitude. Similarly, the HVR A parameter, HCVR S, and HCVR B were not significantly different between the follicular and luteal groups at sea level or high altitude (Table 1). However, the power of the performed ANOVAs of these variables was <0.80. The only arterial blood-gas parameter that was significantly different between the two groups was the resting Pa_CO2 on day 10 at sea level. In five luteal-phase subjects with Pa_CO2 measurements, the Pa_CO2 was lower (2.4 Torr, P = 0.032, 95% CI = 5.0-0.2 Torr) compared with nine follicular-phase subjects at sea level (38.8 ± 1.1 vs. 41.2 ± 0.70 Torr, luteal vs. follicular). Arterial blood gases were not measured in the first 7 days at high altitude. Overall, there were no statistically significant menstrual cycle phase effects on ventilatory acclimatization during the first 7 days of residence at 4,300 m.

Effect of altitude exposure on ventilation. Because there were no statistically significant differences between follicular and luteal groups at high altitude, the data were pooled. Resting PET_CO2 and Sa_O2 were significantly lower and E was greater than at sea level within a few hours of arrival at 4,300 m (Table 2). As indicated by the decreasing PET_CO2, ventilation continued to increase (P < 0.001) throughout the 12 days of high-altitude residence, although the change between days 7 and 12 was not statistically significant. Sa_O2 increased (P < 0.05) rapidly during the first 5 days, with no significant change thereafter. On day 10, resting Pa_CO2, pH_a, and Pa_O2 (28.9 ± 0.6 Torr, 7.446 ± 0.005, and 51.0 ± 1.2 Torr, respectively) were significantly different (P < 0.001) compared with sea-level day 9 (40.4 ± 0.6 Torr, 7.415 ± 0.005, and 107.4 ± 2.8 Torr, respectively). The HVR A parameter and HCVR S were not increased on day 2 but were higher (P < 0.05) by day 7, with no further increase noted on day 12 (Table 2). However, the HCVR B decreased (P < 0.05) from sea-level values on day 2 and continued to fall to day 12. There were no statistically significant changes in resting O₂ between sea level (0.231 ± 0.011 l/min) and any day at high altitude. There were no statistically significant correlations observed between the subjects' ovarian hormone concentrations or estrogen-to-progesterone ratio and resting PET_CO2, HVR A parameter, HCVR S, and HCVR B at sea level or any day at altitude.

Gender comparisons. Plotted in Fig. 1 are the resting PET_CO2 for 37 men at sea level and 4,300 m from Ref. 30 and for the 22 women in the present study. At sea level, resting PET_CO2 was lower (P < 0.001, 95% CI = 4.9 to 1.9 Torr) in the women compared with the men. However, at 4,300 m the women's and men's resting PET_CO2 values were not statistically different. Similarly, there were no significant differences in resting Sa_O2 between the genders throughout the altitude exposure (30). Furthermore, the women's resting Pa_O2 and pH_a measured on day 10 (see above) did not differ from those reported in five men (14) after 10 or 11 days' residence at 4,300 m (48.2 ± 1.2 Torr and 7.449 ± 0.006, respectively). However, in the men, resting Pa_CO2 (25.2 ± 0.85 Torr) was lower (P = 0.003, 95% CI = 1.44-6.01 Torr) compared with that in the women. No statistically significant differences were observed in the women's HVR and HCVR slopes compared with previous studies in men at 4,300 m on days 1, 2, 7, and 14 (27, 43).

View larger version (17K): [in this window] [in a new window]   Fig. 1.   Plot of resting end-tidal PCO2 (PETCO2) measured at sea level (SL) and during 12-day (women) and 19-day (men) sojourns at 4,300 m (Pikes Peak, CO). Women's data are from the present study. Men's data are from Ref. 30. Values are means ± SE. * P < 0.001.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

This study tested the hypothesis that ventilatory acclimatization to high altitude will occur more quickly and to a greater degree in female lowlanders in their early-to-midluteal phase compared with female lowlanders in their follicular phase because of the ventilatory and stimulatory effects of the ovarian hormones in the luteal phase. To this end, indexes of ventilatory acclimatization (resting ventilatory parameters and ventilatory chemosensitivity) were measured at sea level and throughout a 12-day residence at 4,300-m altitude. This cross-sectional data on different women in either the follicular or the luteal phase of the menstrual cycle do not support our hypothesis. Although the luteal group had a significantly lower resting Pa_CO2 at sea level, there were no statistically significant differences between the follicular- and luteal-phase subjects in resting ventilatory parameters or ventilatory chemosensitivity during their residence at high altitude. Similarly, the results do not support our second hypothesis of an expected higher resting effective ventilation and accelerated ventilatory acclimatization in women compared with men. Thus, regardless of menstrual cycle phase, female lowlanders rapidly ascending to 4,300 m have similar levels of alveolar ventilation and follow a time course for ventilatory acclimatization that is nearly identical to that reported in male lowlanders under similar ascent conditions.

There are several possible explanations for our findings. First, we have to consider the limitations of our experimental design. The best experimental design to address our hypothesis would have been a crossover design in which each subject would have gone to altitude twice, once in each phase of their menstrual cycle. However, this design would have required a period of 3-6 mo for deacclimatization between altitude sojourns. Given the limited seasonal access to the Pikes Peak laboratory, a crossover design would have necessitated that each subject maintain adherence to the protocol for ~18 mo. Because of this and other resource limitations, we had to use a between-groups (cross-sectional) design. Thus we may not have observed significant menstrual cycle effects on ventilation because of an inadequate sample size. Based on the previously cited literature, the within-subject, between-phase mean resting PET_CO2 difference is ~2.6 Torr. Prestudy, we expected a similar mean resting PET_CO2 difference between our luteal and follicular groups. Thus, with the use of a standard deviation of 2.4 Torr (31), the calculated sample size to obtain a power >0.80 was 14 subjects for each group. As noted in METHODS, we started with 27 volunteers. However, because of subject withdrawal and several abnormal ovarian hormone profiles, the luteal group lost several subjects, and poststudy the power of the performed ANOVA of resting PET_CO2 between the luteal and follicular groups was only 0.11. Except for the between-groups difference in Pa_CO2 at sea level, our data are absent of even a trend of a difference between the luteal and follicular groups that would be consistent with our hypothesis. Because the interindividual range of resting PET_CO2 was ~10 Torr within either phase of the menstrual cycle, we attempted to minimize between-subject variability by normalizing individual PET_CO2 data (not presented) to sea-level resting PET_CO2. However, even the normalized data did not reveal any significant differences in the ventilatory acclimatization response between the follicular and luteal groups. Recently, Loeppky et al. (22) reported that women had greater ventilation (i.e., lower Pa_CO2) in the luteal compared with follicular menstrual cycle phase at their baseline altitude (~1,646 m) and during 12-h exposure to 4,880 m in a hypobaric chamber. However, the ventilatory difference between the luteal and follicular phases decreased and was not statistically different by the 12th h of altitude exposure (22). This latter finding, as well as ours, suggests that the sustained exposure to hypoxia induces time-dependent changes in ventilatory control that attenuate ovarian hormonal stimulatory effects on ventilation.

Contributing to the absence of a significant menstrual cycle phase effect on ventilatory acclimatization may have been a lack of consistency in when the luteal-phase subjects were studied within their cycle, particularly at high altitude. After ovulation, the time course and magnitude of the normal rise and decline in serum progesterone are quite variable (21). Furthermore, not only are circulating ovarian hormone concentrations important but also progesterone receptor number and their distribution are likely important (7, 16). We do not know what the receptor populations were in our subjects. However, given that all subjects experienced normal cycles, the receptor populations were likely to have been in the normal range. Although attempts were made to test the subjects in their early-to-midluteal phase when progesterone concentrations were likely to be greatest, poststudy analyses of plasma progesterone and estradiol samples suggest that sea-level and high-altitude test days did not always coincide with the subjects' early-to-midluteal phase. In fact, five of eight luteal-phase subjects entered their follicular phase after 5-9 days at high altitude, suggesting that they arrived at 4,300 m in their midluteal rather than early luteal phase. Although serum ovarian hormone concentrations were within accepted clinical limits for normally menstruating women in their luteal phase, the large interindividual variation and lack of concurrence between our subjects' peak ovarian hormone levels and our ventilatory measures may have obscured the ventilatory stimulus effects. However, similar to prior studies (3, 6, 25, 28), we did not find a correlation between progesterone levels and any measure of resting ventilation or chemoresponsiveness at sea level or 4,300 m. On the other hand, at sea level, we measured a within-subject mean resting PET_CO2 difference of 2.2 Torr between the luteal and follicular phases. That observation verifies that the timing and sensitivity of our ventilatory tests were appropriate for measuring menstrual cycle phase differences on resting ventilation and that our subjects exhibited menstrual cycle phase effects on ventilation that were consistent with previous reports (3, 9-12, 20, 23, 31, 34-37, 42).

Inhibitory influences of hypocapnia on the HVR may have suppressed ovarian hormone augmentation of ventilatory acclimatization in the luteal-phase women. On arrival at high altitude, hypocapnia and sustained hypoxia blunt the ventilatory response to the hypobaric hypoxic environment (18). By decreasing central chemoreceptor drive, the hypocapnia may also blunt the stimulant effects of the ovarian hormones on the HVR. At low altitudes, hypocapnia may have contributed to the absence of a clear increase in HVR in the luteal phase of the menstrual cycle (3, 9, 31, 34, 35, 42). Similarly, in studies in which synthetic progestins (medroxyprogesterone acetate) were administered, an increase in HVR was reported in only three of five studies (6, 26, 31, 32, 45) and then only when measured at the higher PET_CO2 present before medroxyprogesterone acetate administration (26, 32, 45). These observations underscore the influence of central chemoreceptor ventilatory drive on the HVR. We did not standardize our measurement of HVR at the same level of central drive for either menstrual cycle phase or elevation (sea level and 4,300 m). Therefore, it is likely that our measurements of HVR are not accurate representations of ovarian hormonal and chronic hypoxic exposure influences on peripheral chemoreceptor sensitivity. Thus the lack of a menstrual cycle phase effect on the HVR at sea level or 4,300 m does not negate the possibility that carotid body activity was increased in the luteal phase in our subjects. Rather, our measurements of HVR reflect the integrated responses of the respiratory controller to the prevailing ovarian hormonal and acid-base milieu. Because women ascending to high altitudes do so under poikilocapnic conditions, our results suggest that menstrual cycle phase influences on ventilation may not be of practical consequence in acclimatizing female lowlanders.

Interindividual differences in ventilation at sea level were more important than menstrual cycle phase in determining subsequent ventilation at high altitude. Sea-level normoxic resting PET_CO2 was related significantly to that at altitude on all days measured. These results in women agree with those previously reported (30) for men at the same altitude and location. The correlations were highest using sea-level resting PET_CO2 values obtained in the same menstrual cycle phase that the subject was in at altitude. This observation suggests that menstrual cycle phase effects on ventilation contribute to the interindividual differences in resting PET_CO2 at sea level and high altitude.

Previous studies of women and men residing at high altitude report greater overall ventilation in women than men (8, 13, 17, 22). In one earlier study on Pikes Peak, female lowlanders had a higher level of effective ventilation (i.e., lower resting Pa_CO2 and higher Pa_O2) during the first 14 days of residence at 4,300 m than did male lowlanders (17). Because we had previously studied the ventilatory acclimatization response in male lowlanders residing in our Pikes Peak laboratory (27, 30, 43), we designed our studies in women to be similar to the studies of these men. As expected (42), at sea level, resting PET_CO2 was lower in the women compared with the men. However, during the nearly 2 wk of high-altitude residence, the women's and men's resting PET_CO2 values were remarkably similar (Fig. 1). Furthermore, other indexes of ventilatory acclimatization (Sa_O2, HVR, HCVR) were not significantly different from those previously measured in men (27, 30, 43). Although the women's resting Pa_O2 and pH_a measured on day 10 did not differ from those reported in men (14) after 10-11 days of residence at 4,300 m, the men's Pa_CO2 values were significantly lower than our women's values, suggesting greater alveolar ventilation in the men. Thus our findings do not agree with the lowlander gender comparisons reported by Hannon (17) at the same high-altitude location. The reason for this difference is unclear. We relied mainly on comparisons of PET_CO2 values to arrive at our conclusion that ventilatory acclimatization follows a similar magnitude and time course in women and men at 4,300 m. On the other hand, Hannon reported differences in arterial blood gases. Interestingly, his reported Pa_O2 values are higher than the corresponding PA_O2 values at high altitude in his subjects. This inconsistency between his arterial and alveolar gas composition data suggests a possible methodological error that may explain the lack of agreement with our results.

The lack of a gender difference in the magnitude and rate of ventilatory acclimatization may be due to lower ventilatory chemosensitivity in women relative to men. White et al. (42) reported that normally menstruating women had a lower HVR than men. Similarly, our women's sea-level isocapnic HVR is lower than reported for men residing at sea level (30). Given the close correlation between sea-level isocapnic HVR and subsequent ventilation at high altitude (18, 30), a lower HVR in women may predispose them to a smaller increase in effective alveolar ventilation during the initial weeks of hypobaric hypoxic exposure. Although our results suggest that women do not acclimatize at a rate or magnitude greater than men do, the previous studies (8, 13, 22) of altitude-acclimatized women showing higher effective alveolar ventilation than men imply that eventually women reestablish their higher levels of alveolar ventilation. Bender et al. (4) found that ventilatory acclimatization in men was complete by day 8 at 4,300 m. Our results in women are essentially similar, in so far as resting PET_CO2 did not change significantly after day 7, although there was a 1.7-Torr decline from days 7 to 12 (Table 2). Over 78 days at 4,300 m, resting PA_O2 rose ~4 Torr from days 14 to 78 (17), suggesting that ventilatory acclimatization may continue in women for a longer period of time than in men. This would reconcile our conclusion that there is no gender effect during the initial weeks of ventilatory acclimatization to high altitude with previous reports (8, 13) of greater effective ventilation in women compared with men after longer term residence at high altitude.

In summary, the data from this cross-sectional study do not support the view that ventilatory acclimatization to high altitude will occur more quickly and to a greater degree in women in their early-to-midluteal phase compared with women in their follicular phase. Independent of menstrual cycle phase, women demonstrated a wide range of interindividual differences in ventilation at sea level and high altitude, and the differences at altitude were related to those present before ascent. Finally, we conclude that female lowlanders rapidly ascending to 4,300 m have similar levels of alveolar ventilation and follow a time course for ventilatory acclimatization that is nearly identical to that reported in male lowlanders under similar ascent conditions.