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Background/Objectives We evaluated potential socioeconomic contributors to variation in Andean adolescents’ growth between households within a peri-urban community undergoing rapid demographic and economic change, between different community types (rural, peri-urban, urban) and over time. Because growth monitoring is widely used for assessing community needs and progress, we compared the prevalences of stunting, underweight, and overweight estimated by three different growth references. Methods Anthropometrics of 101 El Alto, Bolivia, adolescents (Alteños), 11.0–14.9 years old in 2003, were compared between households (economic status assessed by parental occupations); to one urban and two rural samples collected in 1983/1998/1977, respectively; and to the WHO growth reference, a representative sample of Bolivian children (MESA), and a region-wide sample of high-altitude Peruvian children (Puno). Results Female Alteños’ growth was positively associated with household and maternal income indices. Alteños’ height averaged ∼0.8SD/∼0.6SD/∼2SDs greater than adolescents’ height in urban and rural communities measured in 1983/1998/1977, respectively. Overweight prevalence was comparable to the WHO, and lower than MESA and Puno, references. Stunting was 8.5/2.5/0.5 times WHO/MESA/Puno samples, respectively. Conclusions/Implications Both peri-urban conditions and temporal trends contributed to gains in Alteños’ growth. Rural out-migration can alleviate migrants’ poverty, partly because of more diverse economic options in urbanized communities, especially for women. Nonetheless, Alteños averaged below WHO and MESA height and weight medians. Evolved biological adaptations to environmental challenges, and the consequent variability in growth trajectories, favor using multiple growth references. Growth monitoring should be informed by community- and household-level studies to detect and understand local factors causing or alleviating health disparities.

We evaluated potential socioeconomic contributors to variation in Andean adolescents' growth between households within a peri-urban community undergoing rapid demographic and economic change, between different community types (rural, peri-urban, urban) and over time. Because growth monitoring is widely used for assessing community needs and progress, we compared the prevalences of stunting, underweight, and overweight estimated by three different growth references.Anthropometrics of 101 El Alto, Bolivia, adolescents (Alteños), 11.0-14.9 years old in 2003, were compared between households (economic status assessed by parental occupations); to one urban and two rural samples collected in 1983/1998/1977, respectively; and to the WHO growth reference, a representative sample of Bolivian children (MESA), and a region-wide sample of high-altitude Peruvian children (Puno).Female Alteños' growth was positively associated with household and maternal income indices. Alteños' height averaged ∼0.8SD/∼0.6SD/∼2SDs greater than adolescents' height in urban and rural communities measured in 1983/1998/1977, respectively. Overweight prevalence was comparable to the WHO, and lower than MESA and Puno, references. Stunting was 8.5/2.5/0.5 times WHO/MESA/Puno samples, respectively.Both peri-urban conditions and temporal trends contributed to gains in Alteños' growth. Rural out-migration can alleviate migrants' poverty, partly because of more diverse economic options in urbanized communities, especially for women. Nonetheless, Alteños averaged below WHO and MESA height and weight medians. Evolved biological adaptations to environmental challenges, and the consequent variability in growth trajectories, favor using multiple growth references. Growth monitoring should be informed by community- and household-level studies to detect and understand local factors causing or alleviating health disparities.

The idealized “normal” menstrual cycle typically comprises a coordinated ebb and flow of hormones over a 28-day span with ovulation invariably shown at the midpoint. It's a pretty picture—but rare. Systematic studies have debunked the myth that cycles occur regularly about every 28 days. However, assumptions persist regarding the extent and normalcy of variation in other cycle biomarkers. The processes of judging which phenotypic variants are “normal” is context dependent. In everyday life, normal is that which is most commonly seen. In biomedicine normal is often defined as an arbitrarily bounded portion of the phenotype's distribution about its statistical mean. Standards thus defined in one population are problematic when applied to other populations; population specific standards may also be suspect. Rather, recognizing normal female reproductive biology in diverse human populations requires specific knowledge of proximate mechanisms and functional context. Such efforts should be grounded in an empirical assessment of phenotypic variability. We tested hypotheses regarding cycle biomarker variability in women from a wealthy industrialized population (Germany) and a resource-limited rural agropastoral population (Bolivia). Ovulatory cycles in both samples displayed marked but nonetheless comparable variability in all cycle biomarkers and similar means/medians for cycle and phase lengths. Notably, cycle and phase lengths are poor predictors of mid-luteal progesterone concentrations. These patterns suggest that global and local statistical criteria for “normal” cycles would be difficult to define. A more productive approach involves elucidating the causes of natural variation in ovarian cycling and its consequences for reproductive success and women's health.

Objectives We tested 4 main predictions, derived from life history theory and self-evident human diurnality, regarding maternal sleep behaviors in a non-industrialized population in which mother-nursling co-sleeping is universal and prolonged: (1) Night breastfeeding incurs a sleep cost to co-sleeping mothers; (2) Night breastfeeding increases with infant age, causing mothers to sleep less; (3) Sleep duration co-varies with darkness duration; (4) Access to electricity reduces sleep duration. Design Mothers self-recorded and reported nursing and sleep behaviors for a 48-hour period once per month (median = 5 months). Setting Rural Bolivian altiplano homesteads, primarily reliant on agropastoralism, scattered throughout the countryside surrounding a main town (altitude 3800 m; 17°14’S, 65°55’W; darkness duration 10-12 hours over the year). Participants One hundred eighty-four co-sleeping mother-infant pairs (infant age 22-730 days). Measurements Breastfeeding frequency, and retiring and rising times for 885 48-hour observation periods. Results Maternal sleep duration covaried with darkness duration. Sleep duration was shorter in those with access to electricity (ie, living nearer to town) than those without access (more distant homesteads). Night breastfeeding rate was fairly steady until it began to decline after the first year postpartum. At a given infant age, higher night breastfeeding rates were associated with less maternal sleep. As their infants aged, mothers without electricity slept more, whereas mothers with access slept less. Conclusions During the first year postpartum, more frequent night nursing shortens maternal sleep more than any other predictor variable. For older infants, the effect of night nursing diminishes, and even modest “modernization” (eg, access to electricity) is associated with shorter maternal sleep.

The persistently high prevalence of anemia in rural highland Bolivia argues for targeted iron supplementation. We evaluated the cultural, structural and behavioral factors that may facilitate or impede an anemic woman's decision to secure this biomedical treatment from a rural Bolivian health center. Methods Non-pregnant women from a rural town and its surrounding region were tested for anemia. During phase 1 (n = 181), anemic women received a written recommendation for low-cost purchase of iron pills at the nearest health center. They were subsequently interviewed on their actions and experiences. Results Estimated anemia prevalence among these non-pregnant women was 50% higher than the national average. Despite holding conceptualizations of anemia generally aligned with biomedical concepts, only 40% of anemic women attempted to obtain iron supplements from the health center. Town residents were about twice as likely to attempt to purchase pills as outside-town residents. Town women who were concurrently breastfeeding and menstruating, considered anemia most serious for women, and considered family health the shared responsibility of spouses were most likely to decide to purchase iron pills. Age, education, or native language did not negatively influence this health care behavior. Conclusions Securing iron supplements involves individual trade-offs in the allocation of time, cost and effort. Nonetheless, suitably tailored programs can potentially harness local perceptions in the service of reducing anemia. Because of their comparatively high motivation to obtain iron supplements, targeting concurrently breastfeeding and menstruating women could have a positive cascade effect such that these women continue attending to their iron needs once they stop breastfeeding and if they become pregnant again. Because a sense of shared responsibility for family health appears to encourage women to attend to their own health, programs for women could involve their spouses. Complementing centralized availability, biomedical and traditional healers could distribute iron supplements on rotating visits to outlying areas and/or at highly attended weekly markets.

Background We describe here the 3-year process underpinning a multinational collaboration to investigate soccer played at high altitude-La Paz, Bolivia (3600 m). There were two main aims: first, to quantify the extent to which running performance would be altered at 3600 m compared with near sea level; and second, to characterise the time course of acclimatisation of running performance and underlying physiology to training and playing at 3600 m. In addition, this project was able to measure the physiological changes and the effect on running performance of altitude-adapted soccer players from 3600 m playing at low altitude. Methods A U20 Bolivian team ('The Strongest' from La Paz, n=19) played a series of five games against a U17 team from sea level in Australia (The Joeys, n=20). 2 games were played near sea level (Santa Cruz 430 m) over 5 days and then three games were played in La Paz over the next 12 days. Measures were (1) game and training running performance-including global positioning system (GPS) data on distance travelled and velocity of movement; (2) blood-including haemoglobin mass, blood volume, blood gases and acid-base status; (3) acclimatisation-including resting heart rate variability, perceived altitude sickness, as well as heart rate and perceived exertion responses to a submaximal running test; and (4) sleep patterns. Conclusions Pivotal to the success of the project were the strong professional networks of the collaborators, with most exceeding 10 years, the links of several of the researchers to soccer federations, as well as the interest and support of the two head coaches. Refereed/Peer-reviewed

Background Chronic mountain sickness (CMS) is an important public health problem and is characterized by exaggerated hypoxemia, erythrocytosis, and pulmonary hypertension. While pulmonary hypertension is a leading cause of morbidity and mortality in patients with CMS, it is relatively mild and its underlying mechanisms are not known. We speculated that during mild exercise associated with daily activities, pulmonary hypertension in CMS is much more pronounced. Methods We estimated pulmonary artery pressure by using echocardiography at rest and during mild bicycle exercise at 50 W in 30 male patients with CMS and 32 age-matched, healthy control subjects who were born and living at an altitude of 3,600 m. Results The modest, albeit significant difference of the systolic right-ventricular-to-right-atrial pressure gradient between patients with CMS and controls at rest (30.3 ± 8.0 vs 25.4 ± 4.5 mm Hg, P 5 .002) became more than three times larger during mild bicycle exercise (56.4 ± 19.0 vs 39.8 ± 8.0 mm Hg, P Conclusions Measurements of pulmonary artery pressure at rest greatly underestimate pulmonary artery pressure during daily activity in patients with CMS. The marked pulmonary hypertension during mild exercise associated with daily activity may explain why this problem is a leading cause of morbidity and mortality in patients with CMS.

Testosterone (T) plays a key role in the increase and maintenance of muscle mass and bone density in adult men. Life history theory predicts that environmental stress may prompt a reallocation of such investments to those functions critical to survival. We tested this hypothesis in two studies of rural Bolivian adult men by comparing free T levels and circadian rhythms during late winter, which is especially severe, to those in less arduous seasons. For each pair of salivary T(AM)/T(PM) samples (collected in a approximately 12-h period), circadian rhythm was considered classic (C(CLASSIC)) if T(AM)110%T(PM), reverse (C(REVERSE)) if T(PM)110%T(AM), and flat (C(FLAT)) otherwise. We tested the hypotheses that mean T(AM)mean T(PM) and that mean T(LW)mean T(OTHER) (LW = late winter, OTHER = other seasons). In Study A, of 115 T(PM)-T(AM) pairs, 51% = C(CLASSIC), 39% = C(REVERSE), 10% = C(FLAT); in Study B, of 184 T(AM)-T(PM) pairs, 55% = C(CLASSIC), 33% = C(REVERSE), 12% = C(FLAT). Based on fitting linear mixed models, in both studies T(OTHER-AM)T(OTHER-PM) (A: P = 0.035, B: P = 0.0005) and T(OTHER-AM)T(LW-AM) (A: P = 0.054, B: P = 0.007); T(PM) did not vary seasonally, and T diurnality was not significant during late winter. T diurnality varied substantially between days within an individual, between individuals and between seasons, but neither T levels nor diurnality varied with age. These patterns may reflect the seasonally varying but unscheduled, life-long, strenuous physical labor that typifies many non-industrialized economies. These results also suggest that single morning samples may substantially underestimate peak circulating T for an individual and, most importantly, that exogenous signals may moderate diurnality and the trajectory of age-related change in the male gonadal axis.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Objective To test two hypotheses: In spontaneous conceptions, early pregnancy loss (EPL) is associated with [1] inadequate luteal (ovarian) P, and/or [2] elevated follicular (adrenal) P. Design A population-based prospective study. Setting Thirty rural Bolivian communities. Patient(s) Women volunteers (n = 191), 19–40 years old, in stable sexual unions and not using contraception. Intervention(s) Collection of serial saliva samples throughout sequential ovarian cycles and urine samples during late luteal phases. Collections continued throughout pregnancy for each detected conception. Main Outcome Measure(s) Occurrence of spontaneous conceptions and subsequent outcomes. Salivary concentrations of P. Test for elevated urinary human chorionic gonadotropin (hCG). Result(s) Luteal (through implantation) P levels were similar in pregnancies lost within 5 weeks after conception (EPL; n=8) and those pregnancies that were maintained longer (sustained conceptions, SC; n=32). Follicular P was significantly higher in EPL than in SC. Conclusion(s) [1] Elevated follicular P was associated with EPL in natural conceptions in healthy women. [2] Early pregnancy loss exhibits absolute luteal P levels comparable to SC, but lower luteal/follicular P ratios.

For the male inhabitants of La Paz, Bolivia (3200-4100 m), and other high altitude regions in America and Asia, chronic mountain sickness (CMS) is a major health problem. Since CMS was first described by Carlos Monge in the Peruvian Andes in 1925, numerous research papers have been devoted to this topic, but many unanswered questions still exist with respect to the beginning of the disease and its cause(s). The experience with CMS has shown that an excessively high hemoglobin concentration is not favorable for high altitude acclimatization, and the hypothesis of theoretically "optimal" hematocrit and "optimal" hemoglobin has been made. The calculated optimal hemoglobin concentration of 14.7 g/dL for resting men in the Andes is discussed as theoretical and not applicable in real life. The most frequent congenital and acquired heart diseases are discussed, such as patent ductus, atrial septum defect, ventricle septum defect among congenital heart diseases and the still very frequent rheumatic valve cardiopathies and Chagas disease as acquired cardiopathies. Among the typical acquired heart diseases of the high altitude dweller, special attention is given to chronic cor pulmonale as a consequence of severe CMS with pulmonary hypertension.

This study tested the hypothesis that Andean natives are adapted to high altitude (HA) via high work efficiency during exercise in hypoxia. A total of 186 young males and females were tested in Bolivia, comprising eight different subject groups. Groups were identified based on gender, ancestry (Aymara vs. European), altitude of birth (highlands vs. lowlands), and the altitude where tested (420, 3600, 3850 m). This design allows partitioning of ancestral (i.e., genetic) and developmental effects. To minimize measurement error, subjects were given two submaximal exercise tests on a cycle ergometer (on separate days). Each test consisted of four 5-min work bouts (levels), each separated by a 5-min rest period. For all groups, the oxygen consumption (V(O2))-work rate relationship was not different from the sea-level reference. Gross and net efficiencies (GE and NE) were not different between groups at any work level, with the exception of European men born in the lowlands and acclimatized and tested at 3600 m. These men showed slightly lower V(O2) at high work output, but this may be due to a nonsteady-state V(O2) kinetic, rather than to an altered steady-state V(O2)-work rate relationship per se. There were no significant group differences in delta efficiency (DE). In sum, these results provide no support for the hypothesis of energetic advantage during submaximal work in Andean HA natives. A review and analysis of the literature suggest that the same is true for HA natives in the Himalayas.

We developed a simple, non-invasive, and affordable method for estimating net energy expenditure (EE) in children performing activities at high altitude. A regression-based method predicts net oxygen consumption (VO(2)) from net heart rate (HR) along with several covariates. The method is atypical in that, the "net" measures are taken as the difference between exercise and resting VO(2) (DeltaVO(2)) and the difference between exercise and resting HR (DeltaHR); DeltaVO(2) partially corrects for resting metabolic rate and for posture, and DeltaHR controls for inter-individual variation in physiology and for posture. Twenty children between 8 and 13 years of age, born and raised in La Paz, Bolivia (altitude 3,600m), made up the reference sample. Anthropometric measures were taken, and VO(2) was assessed while the children performed graded exercise tests on a cycle ergometer. A repeated-measures prediction equation was developed, and maximum likelihood estimates of parameters were found from 75 observations on 20 children. The final model included the variables DeltaHR, DeltaHR(2), weight, and sex. The effectiveness of the method was established using leave-one-out cross-validation, yielding a prediction error rate of 0.126 for a mean DeltaVO(2) of 0.693 (SD 0.315). The correlation between the predicted and measured DeltaVO(2) was r = 0.917, suggesting that a useful prediction equation can be produced using paired VO(2) and HR measurements on a relatively small reference sample. The resulting prediction equation can be used for estimating EE from HR in free-living children performing habitual activities in the Bolivian Andes.

We tested the hypothesis that ovarian steroids stimulate breathing through a dopaminergic mechanism in the carotid bodies. In ovariectomized female rats raised at sea level, domperidone, a peripheral D2-receptor antagonist, increased ventilation in normoxia (minute ventilation = +55%) and acute hypoxia (+32%). This effect disappeared after 10 daily injections of ovarian steroids (progesterone + estradiol). At high altitude (3,600 m, Bolivian Institute for High-Altitude Biology-IBBA, La Paz, Bolivia), neutered females had higher carotid body tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine synthesis: +129%) and dopamine utilization (+150%), lower minute ventilation (−30%) and hypoxic ventilatory response (−57%), and higher hematocrit (+18%) and Hb concentration (+21%) than intact female rats. Consistent signs of arterial pulmonary hypertension (right ventricular hypertrophy) also appeared in ovariectomized females. None of these parameters was affected by gonadectomy in males. Our results show that ovarian steroids stimulate breathing by lowering a peripheral dopaminergic inhibitory drive. This process may partially explain the deacclimatization of postmenopausal women at high altitude.

SUMMARY At sea level normally menstruating women show increased ventilation (V̇e) and hemodynamic changes due to increased progesterone (P) and estrogen (E2) levels during the mid-luteal (L) compared to the mid-follicular (F) phase of the ovarian cycle. Such changes may affect maximal exercise performance. This repeated-measures, randomized study, conducted at 3600 m, tests the hypothesis that a P-mediated increase in V̇e increases maximal oxygen consumption (V̇O2max) during the L phase relative to the F phase in Bolivian women, either born and raised at high altitude (HA), or resident at HA since early childhood. Subjects (N=30) enrolled in the study were aged 27.7±0.7 years (mean ± s.e.m.) and non-pregnant, non-lactating, relatively sedentary residents of La Paz, Bolivia, who were not using hormonal contraceptives. Mean salivary P levels at the time of the exercise tests were 63.3 pg ml–1 and 22.9 pg ml–1 for the L and F phases, respectively. Subset analyses of submaximal (N=23) and maximal (N=13) exercise responses were conducted only with women showing increased P levels from F to L and, in the latter case, with those also achieving true V̇O2max. Submaximal exercise V̇e and ventilatory equivalents were higher in the L phase (P

Among the most common reasons given for discontinued use of some contraceptive methods is a disturbance in the menstrual cycle, particularly changes in vaginal bleeding. Work to date suggests marked populational variation in menses duration, but few data have been collected from South America. This longitudinal study of non-contracepting Aymara women (n = 189 providing 837 non-truncated bleeding episodes) identified conceptions and fetal loss via urine tests for human chorionic gonadotropin and classified episodes accordingly to test the hypotheses that (a) vaginal bleeding patterns differ between lactating and non-lactating women, (b) duration of vaginal bleeding accompanying fetal loss differs from that of menstruation, (c) menses preceding a conception are longer than those not followed by a conception. Compared to published values, mean menses duration (3.5 days) in these women was relatively short. Menses duration was not significantly correlated with current age, age at menarche or first birth, parity, time postpartum, or menstrual segment length. Mean menses duration (not preceding a conception) was comparable for lactating and non-lactating women. Mean duration of fetal loss bleeding did not differ from that of menses. Pre-conception episodes were significantly longer than those not followed by conception. Thus, because the rate of conceptions was twice as great among lactating than non-lactating women, the mean duration of all menses (irrespective of conception) was significantly longer in lactating women. Bolivian, and perhaps other South American, women may be particularly disinclined to accept contraceptives (e.g., intrauterine devices) that modify an otherwise relatively brief menses duration. Therefore, a wide variety of contraceptive choices accompanied by population-specific informed counseling is essential. In addition, these findings suggest that studies of fecundability limited to non-lactating women may be biased toward those of relatively lower fecundity and that menses duration may be predictive of risk for some cancers.

Choosing an appropriate contraceptive method, particularly one based on fertility awareness, depends in part upon the degree of a woman's cycling regularity. However, while the suppressive effect of lactation on ovarian function is well established, the potential influence of continued breastfeeding on menstrual patterns once post-partum cycling has resumed is largely unexamined. This longitudinal study in a population of non-contracepting Aymara women (n = 191 providing 665 non-truncated menstrual segments) identified conceptions and fetal loss via urine tests for hCG and classified segments accordingly to test the hypotheses that (1) cycles in lactating women are significantly different in length and regularity from those of non-lactating women, and (2) cycles in women living at high altitude are significantly different in length and regularity from those at lower altitudes. Analyses found that segments are significantly longer and regularity tends to be less common among lactating than non-lactating women; however, the rate of conception is twice as great among the former than the latter, and the distribution of conception outcomes does not differ between the two groups. Menstrual regularity is not the norm in this population, even among those who are not currently breastfeeding. High altitude per se does not appear to influence menstrual cycling as both regularity and segment length are comparable to other populations, hence women indigenous to high altitude are suitable candidates for a wide variety of contraceptive choices. In addition, these findings suggest that studies of fecundability limited to non-lactating women may be biased towards those of relatively lower fecundity.

Peak oxygen consumption (VO2peak) was measured in 150 adult males (18–35 years old) in Bolivia, using a complete migrant study design to partition developmental from ancestral (genetic) effects of high-altitude (HA) exposure. High-altitude natives (HANs, Aymara/Quechua ancestry, n = 75) and low-altitude natives (LANs, European/North American ancestry, n = 75) were studied at high altitude (3,600–3,850 m) and near sea level (420 m). HAN and LAN migrant groups to a nonnative environment were classified as: multigeneration migrants, born and raised in a nonnative environment; child migrants who migrated to the nonnative environment during the period of growth and development (0–18 years old); and adult migrants who migrated after 18 years of age. Variability in VO2peak due to high-altitude adaptation was modeled by covariance analysis, adjusting for fat-free mass and physical activity (training) differences between groups. A trend for increased VO2peak with increasing developmental high-altitude exposure in migrant groups did not reach statistical significance, but low statistical power may have limited the ability to detect this effect. HANs and LANs born, raised, and tested at high altitude had similar VO2peak values, indicating no genetic effect, or an effect much smaller than that reported previously in the literature. There was no functional correlation between forced vital capacity and VO2peak, within or across groups. These results do not support the hypothesis that Andean HANs have been selected to express a greater physical work capacity in hypoxia. Am J Phys Anthropol 110:435–455, 1999. © 1999 Wiley-Liss, Inc.

Favier, R., E. Caceres, B. Sempore, J. M. Cottet-Emard, G. Gauquelin, C. Gharib, and H. Spielvogel. Fluid regulatory hormone response to exercise after coca-induced body fluid shifts. J. Appl. Physiol. 83(2): 376–382, 1997.—To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at ∼75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca− trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca− and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca−), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (−3.8 ± 1.3% in blood and −7.0 ± 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.

The present study was undertaken to determine the haematological and cardiovascular status, at rest and during prolonged (1 h) submaximal exercise (approximately 70% of peak oxygen uptake) in a group (n = 12) of chronic coca users after chewing approximately 50 g of coca leaves. The results were compared to those obtained in a group (n = 12) of nonchewers. At rest, coca chewing was accompanied by a significant increase in heart rate [from 60 (SEM 4) TO 76 (SEM 3) beats · min−1], in haematocrit [from 53.2 (SEM 1.2) to 55.6 (SEM 1.1)%] in haemoglobin concentration, and plasma noradrenaline concentration [from 2.8 (SEM 0.4) to 5.0 (SEM 0.5) μmol · l−1]. It was calculated that coca chewing for 1 h resulted in a significant decrease in blood [−4.3 (SEM 2.2)%] and plasma [−8.7 (SEM 1.2)%] volume. During submaximal exercise, coca chewers displayed a significantly higher heart rate and mean arterial blood pressure. The exercise-induced haemoconcentration was blunted in coca chewers compared to nonchewers. It was concluded that the coca-induced fluid shift observed at rest in these coca chewers was not cumulative with that of exercise, and that the hypovolaemia induced by coca chewing at rest compromised circulatory adjustments during exercise.

Objectives The optimal strategy for soccer teams playing at altitude is not known, that is, ‘fly-in, fly-out’ versus short-term acclimatisation. Here, we document changes in blood gas and vascular volumes of sea-level (Australian, n=20) and altitude (Bolivian, n=19) native soccer players at 3600 m. Methods Haemoglobin-oxygen saturation (Hb-sO 2 ), arterial oxygen content (CaO 2 ), haemoglobin mass (Hbmass), blood volume (BV) and blood gas concentrations were measured before descent (Bolivians only), together with aerobic fitness (via Yo-YoIR1), near sea-level, after ascent and during 13 days at 3600 m. Results At baseline, haemoglobin concentration [Hb] and Hbmass were higher in Bolivians (mean±SD; 18.2±1.0 g/dL, 12.8±0.8 g/kg) than Australians (15.0±0.9 g/dL, 11.6±0.7 g/kg; both p≤0.001). Near sea-level, [Hb] of Bolivians decreased to 16.6±0.9 g/dL, but normalised upon return to 3600 m; Hbmass was constant regardless of altitude. In Australians, [Hb] increased after 12 days at 3600 m to 17.3±1.0 g/dL; Hbmass increased by 3.0±2.7% (p≤0.01). BV decreased in both teams at altitude by ∼400 mL. Arterial partial pressure for oxygen (PaO 2 ), Hb-sO 2 and CaO 2 of both teams decreased within 2 h of arrival at 3600 m (p≤0.001) but increased over the following days, with CaO 2 overcompensated in Australians (+1.7±1.2 mL/100 mL; p≤0.001). Yo-YoIR1 was lower on the 3rd versus 10th day at altitude and was significantly related to CaO 2 . Conclusions The marked drop in PaO 2 and CaO 2 observed after ascent does not support the ‘fly-in, fly-out’ approach for soccer teams to play immediately after arrival at altitude. Although short-term acclimatisation was sufficient for Australians to stabilise their CaO 2 (mostly due to loss of plasma volume), 12 days appears insufficient to reach chronic levels of adaption.

The aim of this work was to evaluate the effects of high altitude and low socioeconomic status (SES) on aerobic and anaerobic power in 11-yr-old Bolivian girls. At both high (3,600 m) and low (420 m) altitudes, low-SES groups of girls were compared to similarly aged, high-SES girls. At low altitude, low-SES girls were also compared with younger high-SES girls with the same anthropometric characteristics. Anthropometric data were similar between high-SES and low-SES girls at both altitudes, but low-SES girls showed a 9-mo growth delay. Maximal O2 uptake was significantly lower for low-SES girls at both altitudes. Values did not differ when expressed relative to body weight at high altitude for high-SES vs. low-SES girls (37.6 +/- 1.2 vs. 39.3 +/- 1.0 ml.min-1.kg body wt-1), but a difference persisted at low altitude between high- and low-SES girls (37.5 +/- 1.0 vs. 34.7 +/- 0.7 ml.min-1.kg body wt-1). Anaerobic power (Pmax, force-velocity test; Pwing, Wingate test) was reduced for low-SES girls at both altitudes, whatever the mode of expression. For a given SES, the relative anaerobic performances were lower at low altitude. At low altitude, low-SES girls developed lower anaerobic power than did younger high-SES girls with similar anthropometric characteristics. In conclusion, at both altitudes, the reduction of anaerobic performances observed in girls of low SES could not be totally explained by anthropometric factors. Structural and/or functional muscle alterations are suggested. Moreover, at low altitude, tropical and other factors may have contributed to differences in performance between low- and high-SES girls.

The effects of coca chewing on prolonged submaximal exercise responses were investigated in chronic coca chewers and compared with a group of nonchewers. At rest, coca chewing during a 1-h period was followed by a significant increase in blood glucose, free fatty acid, and norepinephrine concentrations and a significant reduction in insulin plasma level. During prolonged (1-h) submaximal (65-70% peak O2 uptake) exercise, chewers displayed a significantly greater adrenergic activation (as evidenced by a higher level of plasma epinephrine) and an increased use of fat (as evidenced by a lower respiratory exchange ratio). The gradual increase in oxygen uptake (O2 drift) commonly observed during prolonged exercise was blunted in coca chewers. This blunting in O2 drift is not related to coca-induced changes in ventilatory or lactate responses to exercise but could possible be related to an enhanced glucose utilization by chewers during the late phase of exercise. The present results provide experimental evidence of the physiological effects of coca chewing that could explain the better ability of coca users to sustain strenuous work for an extended period of time.

Maximal O2 uptake (VO2max) was determined on a bicycle ergometer in chronic hypoxia (CH) and during acute exposure to normoxia (AN) in 50 healthy young men who were born and had lived at 3,600 m altitude (La Paz, Bolivia). VO2max was significantly improved (approximately 8%) by AN. However, the difference in VO2max measured in CH and AN (delta VO2max) was lower than that reported in sea-level natives (SN) who exercised in chronic normoxia and acute hypoxia. It is shown that high-altitude natives (HN) and SN have a similar VO2max in normoxia, but highlanders can attain a greater VO2max when O2 availability is reduced by altitude exposure. In addition, in HN, the higher the subject's VO2max in hypoxia, the smaller his delta VO2max. These results contrast with the data obtained in 14 lowlanders acclimatized to high altitude who showed that their delta VO2max was positively related to their VO2max in hypoxia, as previously reported in SN who exercised in acute hypoxia (A. J. Young, A. Cymerman, and R. L. Burse. Eur. J. Appl. Physiol. Occup. Physiol. 54: 12–15, 1985). Furthermore, arterial O2 saturation of HN behaved differently from acclimatized lowland natives, inasmuch as it fell less during exercise both in CH and AN. HN with high aerobic capacity display a lower exercise ventilation and a reduced arterial saturation, which could explain their inability to improve VO2max with normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

The aerobic capacity of 268 subjects (158 males and 110 females) was evaluated in La Paz, Bolivia situated at 3,750 m. The sample included 1) 39 high altitude rural natives (all male); 2) 67 high altitude urban natives (32 male, 35 female); 3) 69 Bolivians of foreign ancestry acclimatized to high altitude since birth (37 male, 32 female); 4) 50 Bolivians of foreign ancestry acclimatized to high altitude during growth (25 male, 25 female); and 5) 42 non-Bolivians of either European or North American ancestry acclimatized to high altitude during adulthood (25 male, 18 female). Data analyses indicate that 1) high altitude urban natives, acclimatized to high altitude since birth or during growth, attained higher aerobic capacity than subjects acclimatized to high altitude during adulthood; 2) age at arrival to high altitude is inversely related to maximum oxygen consumption (VO2 max) expressed in terms L/min or ml/min/kg of lean body mass, but not in terms of ml/min/kg of body weight; 3) among subjects acclimatized to high altitude during growth, approximately 25% of the variability in aerobic capacity can be explained by developmental factors; 4) as inferred from evaluations of skin color reflectance and sibling similarities, approximately 20 to 25% of the variability in aerobic capacity at high altitude can be explained by genetic factors; 5) except among the non-Bolivians acclimatized to high altitude during adulthood, the aerobic capacity of individuals with high occupational activity level is equal to the aerobic capacity of high altitude rural natives; and 6) the relationship between occupational activity level and aerobic capacity is much greater among subjects acclimatized to high altitude before the age of 10 years than afterwards. Together these data suggest that the attainment of normal aerobic capacity at high altitude is related to both developmental acclimatization and genetic factors but its expression is highly mediated by environmental factors, such as occupational activity level and body composition.

The leaves of the coca plant (Erythroxylum sp.) have long been chewed by natives of the highland Andes. Folk belief is that the mild stimulant effect is indispensable as an ergogenic aid for strenuous work activities in a high altitude environment. This study explored the exercise responses of 23 nonhabitual coca chewing males who were asked to pedal a bicycle ergometer through a series of submaximal and maximal workloads both with and without coca chewing. The protocol of the exercise test was specifically designed to allow for the determination of work and muscular efficiencies during to submaximal work. The subjects showed no differences between the coca and control work protocols for VO2 max (1/min), VCO2 max (1/min), or maximal work output (watts). Further, there were no differences between coca and control work protocols in oxygen saturation (%), pulmonary ventilation (1/min), or respiratory exchange ratio (VCO2 /VO2 ) at any level of work. Coca chewing caused subjects to have a higher heart rate (bpm) and lower oxygen pulse (ml/beat) for most submaximal workloads and higher ventilatory equivalents (VE/VO2 and VE/VCO2 ) above 50% of VO2 max. Although there was a tendency for higher gross efficiencies (GE) during the coca exercise test at lower relative work levels, between 30-40% of the VO2 max, this difference did not reach significance. Mean net efficiency (NE) was higher (P=0.018) at a relative work level of ∼32% of the VO2 max for exercise with coca (23.2% vs. 20.8%). This difference was not apparent at any other work level. The mean delta efficiency (DE) was significantly lower (P = 0.012) for exercise with coca (26.7%) than for exercise without coca (28.2%). These efficiency differences suggest a muscle metabolic effect for coca chewing at low workloads whereby less oxygen is consumed by the muscle to perform a given work task. Howeve, given the difficulty of interpreting efficiency values, it is not entirely clear if the differences are indicative of a work performance benefit for coca chewing. © 1995 Wiley-Liss, Inc.

The aim of this study was to analyze the effect of altitude and socioeconomic status on the maximal oxygen uptake (VO2max) of prepubertal Bolivian boys. The subjects were 143 prepubertal boys (10 to 11.5 years old) living in La Paz (altitude 3600 m, n = 67) and Santa Cruz de la Sierra (altitude 420m, n = 76). At high altitude, 23 boys were from a high socioeconomic status (HAHSES) and 44 from a low socioeconomic background (HALSES). At low altitude, 29 boys were from a high socioeconomic level (LAHSES) and 47 from a low socioeconomic background (LALSES). Anthropometric characteristics were determined in order to assess the physical growth of the boys. The VO2max was determined from a progressive maximal exercise (direct method). The subjects performed this test using the same cycle ergometer at both high and low altitudes. For the overall anthropometric parameters, there was no significant difference between highland and lowland boys of the same socioeconomic status. However, regardless of altitude, boys from a low socioeconomic background were 2 years behind those from a high socioeconomic background. There was no significant difference for VO2max between boys from high and low socioeconomic backgrounds at HA (HAHSES: 37.2 +/- 5.6; HALSES: 38.9 +/- 6.4 ml.min-1.kg-1 body weight) and at LA (LAHSES: 42.6 +/- 5.4; LALSES: 43.1 +/- 4.9 ml.min-1.kg-1 body weight). The VO2max of highland boys was, on average, 11% lower than that of lowland boys. It appears, therefore, that a difference in socioeconomic status has no effect on the VO2max (ml.min-1.kg-1) of prepubertal children at low altitude as well as the altitude of 3600m.

The aim of this work was to study the effect of hypoxic stress on the physical growth of prepubertal Bolivian boys (10-11.5 years of age) of the same socioeconomic and nutritional conditions. The subjects consisted of 143 boys living in La Paz (altitude 3600 m, n = 67) and Santa Cruz de la Sierra (altitude 420 m, n = 76). Among the boys studied at high altitude, 23 were from a high socioeconomic background (HA1) and 44 from a low socioeconomic background (HA2). The group studied at low altitude consisted of 47 boys from a high socioeconomic background (LA1) and 29 from a low socioeconomic background (LA2). A scientific evaluation of the nutritional status of the boys was realized from specific anthropometric characteristics (height, body weight, upper arm muscle circumference, body fat mass and body mass index) and haematological (haematocrit, haemoglobin, serum iron, serum ferritin, red cell protoporphyrin, transferrin saturation) and biochemical (total serum protein, albumin and prealbumin) parameters. At high as at low altitudes, the biometric characteristics of boys from a low socioeconomic background were significantly lower than those of boys from a high socioeconomic background. The physical growth of HA2 and LA2 boys was delayed by approximately 2 years. All the boys had biochemical and haematological parameters within the normal range. Boys from a low socioeconomic background were considered as marginally undernourished and those from a high socioeconomic background as well-nourished. Within the same socioeconomic class there was no nutritional difference between highland and lowland boys. Similarly, and this is the most important feature of this study, there was no difference for the overall biometric characteristics between highland and lowland boys of the same socioeconomic and nutritional status. Therefore, it appears that when socioeconomic and nutritional conditions are taken into account, there is no effect of hypoxic stress on the physical growth of prepubertal Andean highland boys.

Field tests of running and laboratory tests were performed in La Paz [high altitude (HA), 3700 m] and in Clermont-Ferrand [low altitude (LA), 300 m] to investigate their validity at HA. Prepubertal boys of mean ages 10.6 years (HA1,n = 16; LA1,n = 28) and pubertal boys of 13.7 years (HA2,n = 12; LA2,n = 41) took part in the study. All the boys performed a 30-m sprint (v30m), a 30-s shuttle run (v3os) and a progressive shuttle run test until their maximal aerobic velocity (vmaxsRT). Maximal oxygen consumption was extrapolated from the last test.\(\left( {\dot VO_{2maxSRT} } \right)\). In the laboratory, the boys performed a force-velocity test (Pmax), a Wingate test (PWing) and a graded test to measure maximal oxygen consumption\(\left( {\dot VO_{2maxB} } \right)\); direct method) on a cycle ergometer. At similar ages, there was no significant difference between HA and LA boys forv30m andPmax. Thev30s of HA boys was 3%–4% lower than those of LA boys (P

Life history theory predicts that early pregnancy presents a relatively low cost, uncontested opportunity for a woman to terminate investment in a current reproductive opportunity if a conceptus is of poor quality and/or maternal status or environmental conditions are not propitious for a successful birth. We tested this hypothesis in rural Bolivian women experiencing substantial seasonal variation in workload and food resources. Significant risk factors for early pregnancy loss (EPL) included agropastoralism versus other economic strategies, conception during the most arduous seasons versus other seasons, and increasing maternal age. Anovulation rate (AR) was higher during the most arduous seasons and in older women. Breastfeeding and indicators of social status and living conditions did not significantly influence either risk of EPL or AR. Averaged over the year, anovulation occurred in about 1/4 of the cycles and EPL occurred in about 1/3 of the conceptions. This is the first evidence of seasonality of EPL in a non-industrialized population, and the first to demonstrate a relationship between economic activities and EPL. These findings suggest that both anovulation and EPL are potential mechanisms for modulating reproductive effort; such "failures" may also be nonadaptive consequences of conditions hostile to a successful pregnancy. In either case, variation in EPL risk associated with different subsistence activities can be expected to influence fertility levels and birth seasonality in both contemporary and past human populations. These consequences of variability in the risk of EPL can impact efforts to understand the sources of variation in reproductive success.

The skin reflectance of 556 Andean Indians of Aymara ancestry (305 males, 251 females; 10.0-29.9 yr) residing in La Paz, Bolivia (average altitude of about 3,600 m) is described. Reflectances were measured at three wavelengths (425 nm, 545 nm, and 685 nm) on two different sites, the medial surface of the upper arm and forehead. Males tended to be significantly darker than females on both the upper arm and forehead (P < .05). Female Aymara tended to lighten significantly in skin color with age on both the upper arm and forehead, while males tended to lighten significantly with age only on the upper arm (P < .05). The results of comparisons between three categories based on paternal and maternal surnames (two Aymara surnames, one Aymara and one Spanish surname, and two Spanish surnames) were consistent with the hypothesis that the possession of Spanish surnames is positively related to the degree of European admixture in urban Aymara. However, the extent of admixture within each surname category may differ between rural and urban Aymara, making classification by surnames problematic for rural-urban comparisons.

Clinical studies of women from the United States demonstrate a sensitivity of the ovarian system to energetic stress. Even moderate exercise or caloric restriction can lead to lower progesterone levels and failure to ovulate. Yet women in many nonindustrial populations experience as many as a dozen pregnancies in a lifetime despite poor nutritional resources, heavy workloads, and typical progesterone levels only about two-thirds of those of U.S. women. Previous cross-sectional studies of progesterone may, however, suffer from inadvertent selection bias. In a noncontracepting population, the most fecund women, who might be expected to have the highest progesterone, are more likely to be pregnant or breastfeeding and hence unavailable for a cross-sectional study of the ovarian cycle. The present longitudinal study was designed to ascertain whether lower progesterone also characterizes conception, implantation, and gestation in women from nonindustrialized populations. We compared rural Bolivian Aymara women ( n = 191) to women from Chicago ( n = 29) and found that mean-peak-luteal progesterone in the ovulatory cycles of Bolivian women averaged ≈71% that of the women from Chicago. In conception cycles, progesterone levels in Bolivian women during the periovulatory period were ≈63%, and during the peri-implantation period were ≈50%, those of the U.S. women. These observations argue that lower progesterone levels typically characterize the reproductive process in Bolivian women and perhaps others from nonindustrialized populations. We discuss the possible proximate and evolutionary explanations for this variation and note the implications for developing suitable hormonal contraceptives and elucidating the etiology of cancers of the breast and reproductive tract.

In concert with improving standards of living since the mid-19th century, chronic and non-infectious diseases replaced infectious diseases as the major causes of mortality in more developed countries. Thus, economic development has been seen as one strategy to improve women’s reproductive health. However, rates of two of the major contributors to women’s illness, maternal mortality and breast cancer, do not correspond well with the level of economic development. Drawing upon our longitudinal study of reproductive functioning among rural Bolivians (Project Reproduction and Ecology in Provincia Aroma (REPA)), we propose an evolutionary model to explain variation in certain aspects of women’s reproductive health. Our findings suggest new avenues of inquiry into the determinants of reproductive health and have implications for improving the well-being of women worldwide.

In Bolivia, malnutrition in children is a major health problem that may be caused by inadequate protein, energy, and micronutrient intake; exposure to bacterial and parasitic infections; and life in a multistress environment (high altitude, cold, cosmic radiation, low ambient humidity). However, no data on protein absorption and utilization at high altitude were available. Therefore, we evaluated the effect of altitude on protein metabolism in Bolivian children. We measured protein utilization using leucine labeled with a stable isotope ((13)C) in two groups of healthy prepubertal children matched for age. Group 1 (n = 10) was examined at high altitude (HA) in La Paz (3600 m), and group 2 (n = 10) at low altitude (LA) in Santa Cruz (420 m). The nutritional status did not differ between groups but, as was to be expected, the HA group had higher hemoglobin concentration than the LA group. The children consumed casein that was intrinsically labeled with L-(1-(13)C) leucine and expired (13)CO(2) was analyzed. Samples of expired air were measured by isotope ratio mass spectrometer in Clermont-Ferrand. It was found that cumulative leucine oxidation ((13)CO(2)) at 300 min after ingestion was 19.7 +/- 4.9% at HA and 25.2 +/- 3.2% at LA. These results showed that protein absorption and/or utilization is significantly affected by altitude.

BACKGROUND: Agriculturalists in less-developed countries (LDC) have lower progesterone levels than urban industrialized populations. However, it is unknown if urban LDC populations are also relatively lower. We tested whether urban Bolivia samples—poorer (Bol-p) and better-off (Bol-b)—have lower progesterone than a Chicago (USA) sample, and whether progesterone and rate of ovulation are lower in Bol-p than in Bol-b. METHODS: Serial salivary samples collected from Bolivians, screened according to strict exclusion criteria during two complete menstrual cycles, were radioimmunoassayed for progesterone; anthropometrics were collected at mid-follicular and mid-luteal phases. RESULTS: Progesterone levels are lower in the Bolivia samples, and higher in the Bol-b than Bol-p; ovulation rate is greater in Bol-b than Bol-p. For only ovulatory cycles, mean-follicular-P (pmol/l), mean-luteal-P (pmol/l), and mean-peak-P (pmol/l) are respectively 65, 142 and 208 in Bol-p; 76, 167 and 232 in Bol-b; and 96, 240 and 330 in Chicago. Principal components representing body-size and progesterone level are positively correlated (r = 0.404, P = 0.005). CONCLUSIONS: Progesterone levels appear to be influenced by chronic and acute ecological conditions, evidenced by the association with body-size and the probability of ovulation respectively. These findings have implications for understanding cancer aetiology, developing population-appropriate hormonal contraceptives, and modelling the evolution and functioning of the reproductive system.

Pulmonary gas exchange and acid-base state were compared in nine Danish lowlanders (L) acclimatized to 5,260 m for 9 wk and seven native Bolivian residents (N) of La Paz (altitude 3,600–4,100 m) brought acutely to this altitude. We evaluated normalcy of arterial pH and assessed pulmonary gas exchange and acid-base balance at rest and during peak exercise when breathing room air and 55% O2. Despite 9 wk at 5,260 m and considerable renal bicarbonate excretion (arterial plasma HCO3 − concentration = 15.1 meq/l), resting arterial pH in L was 7.48 ± 0.007 (significantly greater than 7.40). On the other hand, arterial pH in N was only 7.43 ± 0.004 (despite arterial O2 saturation of 77%) after ascent from 3,600–4,100 to 5,260 m in 2 h. Maximal power output was similar in the two groups breathing air, whereas on 55% O2only L showed a significant increase. During exercise in air, arterial Pco 2 was 8 Torr lower in L than in N ( P < 0.001), yet Po 2 was the same such that, at maximal O2 uptake,alveolar-arterial Po 2 difference was lower in N (5.3 ± 1.3 Torr) than in L (10.5 ± 0.8 Torr), P = 0.004. Calculated O2 diffusing capacity was 40% higher in N than in L and, if referenced to maximal hyperoxic work, capacity was 73% greater in N. Buffering of lactic acid was greater in N, with 20% less increase in base deficit per millimole per liter rise in lactate. These data show in L persistent alkalosis even after 9 wk at 5,260 m. In N, the data show 1) insignificant reduction in exercise capacity when breathing air at 5,260 m compared with breathing 55% O2; 2) very little ventilatory response to acute hypoxemia (judged by arterial pH and arterial Pco 2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial Po 2despite lower ventilation; and 4) better buffering of lactic acid. These results support and extend similar observations concerning adaptation in lung function in these and other high-altitude native groups previously performed at much lower altitudes.

Chest depth, chest width, forced vital capacity (FVC), and forced expiratory volume (FEV1) were measured in 170 adult males differing by ancestral (genetic) and developmental exposure to high altitude (HA). A complete migrant study design was used to study HA natives (Aymara/Quechua ancestry, n = 88) and low altitude (LA) natives (European/North American ancestry, n = 82) at both altitude (La Paz, Bolivia, 3,600 m) and near sea level (Santa Cruz, Bolivia, 420 m). HAN and LAN migrant groups were classified as: N(th) generation migrants, born and raised in a non-native environment; child migrants who migrated during the period of growth and maturation (0-18 yrs); and adult migrants who migrated after 18 years of age. Chest depth, FVC, and FEV1 measures were larger with increasing developmental exposure in both HAN migrants at LA and LAN migrants at HA. Developmental responses were similar between HAN and LAN groups. FVC and FEV1 measures were larger in HANs vs LANs born and raised at HA to suggest a genetic effect, but were similar in HANs and LANs born and raised at LA. The similarity of HAN and LAN groups at LA suggests that the genetic potential for larger lung volumes at HA depends upon developmental exposure to HA. Additional data for females (HANs at HA, n = 20, and LAN adult migrants to HA, n = 17) show similar differences as those shown between male HAN and LAN groups. Am. J. Hum. Biol. 11:383-395, 1999. Copyright 1999 Wiley-Liss, Inc.

Fertility appears to be reduced in at least some high altitude populations relative to their counterparts at lower elevations. Inferring from the difficulties with reproduction of newcomers to high altitude and from animal experiments, it has been hypothesized that this apparent reduction is the result of hypoxia acting to reduce fecundity and/or increase fetal loss. In humans, however, several behavioral as well as biological factors may affect fertility levels. These many factors have been organized by demographers into a framework of seven proximate determinants that includes fecundability (the monthly probability of conception) of which successful ovulation is one component. To test whether ovarian function is impaired in women indigenous to high altitude, we measured salivary progesterone (P) in a sample (n = 20) of Quechua women (aged 19-42 years) residing at 3,100 m. It was found that mean luteal P = 179 pmol/L and mean midluteal P = 243 pmol/L, levels that fall about midway in the range of known values for several populations and are higher than some lower altitude populations. These findings suggest that hypoxia does not appear to significantly impair ovarian function in those with lifelong residence at high altitude. There are, however, several factors common to many high altitude populations that may act to reduce fecundability and fertility including intercourse patterns (affected by marriage and migration practices), prolonged lactation, dietary insufficiency, and hard labor.

Arterial oxygen saturation (SaO2) was measured at 3,600–3,850 m by pulse oximetry at rest and during submaximal exercise in three study groups: 1) highland Aymara natives of the Bolivian altiplano (n = 25); 2) lowland European/North American sojourners to the highlands with at least 2 months of acclimatization time to 3,600 m (n = 27); and 3) subjects of European ancestry born and raised at 3,600 m (n = 22). Aymara subjects maintained ∼1 percentage point higher SaO2 during submaximal work up to 70% of their maximal work capacity, and showed a smaller rate of decline in SaO2 with increasing work compared to both European study groups. The higher-exercise SaO2 of Aymara compared to Europeans born and raised at 3,600 m suggests genetic adaptation. The two European study groups, who differed by exposure to high altitude during their growth and development period, did not show any significant difference in either resting or exercise SaO2. This suggests that the developmental mode of adaptation is less important than the genetic mode of adaptation in determining exercise SaO2. A weak correlation was detected (across study groups only) between the residual forced vital capacity (FVC) and the residual SaO2 measured at the highest level of submaximal work output (P = 0.024, R = 0.26). While firm conclusions based on this correlation are problematic, it is suggested that a part of the higher SaO2 observed in Aymara natives is due to a larger lung volume and pulmonary diffusion capacity for oxygen. Results from this study are compared to similar studies conducted with Tibetan natives, and are interpreted in light of recent quantitative genetic analyses conducted in both the Andes and Himalayas. Am J Phys Anthropol 113:169–181, 2000. © 2000 Wiley-Liss, Inc.

The effect of chronic hypoxia on gender differences in physiology and neurochemistry of chemosensory pathways was studied in prepubertal and adult rats living at sea level (SL; Lyon, France) or at high altitude (HA; La Paz, Bolivia, 3,600 m). HA adult rats had higher hematocrit (Ht%), Hb concentration, resting ventilatory rate (Ve100), and higher tyrosine hydroxylase (TH) activity in carotid bodies (CB) than SL animals. At HA and SL, adult females had lower Ht% (46.0 ± 0.8 vs. 50.4 ± 0.6% at HA, P < 0.05 and 43.8 ± 0.9 vs. 47.1 ± 0.8% at SL, P < 0.05) and Hb (16.1 ± 0.3 vs. 17.7 ± 0.2 g/dl at HA, P < 0.05 and 14.5 ± 0.3 vs. 15.6 ± 0.1 g/dl at SL, P < 0.05) than males. Females had higher Ve100 [170 ± 19 vs. 109 ± 7 ml ⋅ min− 1 ⋅ 100 g− 1 at HA, P < 0.05 and 50 ± 3 vs. 40 ± 2 ml ⋅ min− 1 ⋅ 100 g− 1 at SL, not significant (NS)] and lower CB-TH activity (1.40 ± 0.2 vs. 3.87 ± 0.6 pmol/20 min at HA, P < 0.05 and 0.52 ± 0.1 vs. 0.68 ± 0.1 pmol/20 min at SL; NS) than males at HA only. The onset of hypoxic ventilatory response during development was delayed at HA. Prepubertal HA females had higher Ve100 than males (2 wk old, +47%) and higher CB-TH activity (3 wk old, +51%). Medullary noradrenergic groups were sex dimorphic during development at SL. Rats raised at HA had a drop of TH activity between the second and the third postnatal week in all medullary groups. In conclusion, our data support the hypothesis that the CB is the major site for sexual differentiation of the ventilatory control. Ventilatory differences appeared before puberty, and the animals bred at HA had profound alterations in the developmental process of the chemoreflex and its neural pathways. Some of these alterations are under dependence of the sex of the animal, and there is an important interaction between gender and the hypoxic environmental condition during the developmental period.

At the highest altitude, aerobic work is limited by environmental oxygen availability. We therefore reasoned that the hyperpnea associated with endurance training at altitude should provide a strong stimulus for adaptation of the ventilatory muscles. We measured peak inspiratory muscle pressure-flow characteristics (inspiring through graded resistors) and maximum sustainable ventilation capacity in ten permanent residents of La Paz, Bolivia (3600 m) prior to and immediately following 6 weeks of incremental endurance training. Additionally, eight local residents did no training and functioned as controls for the capacity test. While V(O2)max measured in hypoxia increased by 19% (Favier et al., 1995b. J. Appl Physiol. 78, 2286-2293.), none of the tested ventilatory variables showed significant changes. The values for the group mean slopes of maximum inspiratory pressure-flow pairs (- 10.5 vs. - 9.8 cm H2O x sec x L(-1), P=0.301; before versus after training, respectively), maximum inspiratory pressure (112.1+/-8.9 vs. 106.9+/-8.6 cmH2O, P=0.163), peak inspiratory flow (9.8+/-0.41 vs. 10.2+/-0.55 L x sec(-1) P=0.172) and the maximum volitional volume in 12 sec (43.9+/-2.4 vs. 45.6+/-2.4 L in 12 sec, P=0.133) were unchanged with exercise training. Likewise, maximal sustainable minute volume was not different between post-training and control subjects (177.4+/-7.9 vs. 165.4+/-8.4 L x min(-1), P=0.141). These data support the concept that endurance training fails to elicit functional adaptations in ventilatory muscles in humans, even when exercise is done in hypoxia.

In the absence of pulmonary disease, hypoventilation is considered to be the primary cause of Chronic Mountain Sickness, and there is some reason to believe that chronic administration of respiratory analeptics could be useful for treatment of this disease. The present study was intended to define comparatively the influence of two potent ventilatory stimulants, namely a combination of progesterone and estrogen and the pharmacological agent almitrine, on catecholaminergic structures implicated in the chemoreflex pathway and on hypoxia-induced polycythemia. Three groups of young male rats born and living at high altitude (3 600 m) were examined: untreated animals (n = 25), rats given ovarian steroids (progesterone plus 17beta-estradiol, n = 25) or almitrine (n = 25) for 6 weeks until sacrifice. Ovarian steroids or almitrine had pronounced neurochemical effects on the afferent chemoreflex circuitry. Both treatments inhibited norepinephrine (NE) and dopamine (DA) turnover in the carotid body, but central processing of chemosensory inputs differed between the two respiratory drugs. Ovarian steroids inhibited noradrenergic activity in the projection area of the chemosensory nerve fibers within the caudal portion (A2C) of the nucleus tractus solitarius (NTS). In contrast, almitrine stimulated neurochemical activity of other brainstem noradrenergic cell groups involved in cardiorespiratory control, i.e. , the rostral portion (A2R) of the NTS, the nucleus reticularis lateralis (A1), the nucleus olivaris superior (A5) and the locus ceruleus (A6). Although both treatments increased chemoreflex drive and ventilation, only sex hormones decreased erythropoietin (EPO) levels and the degree of polycythemia. These results suggest that stimulation of ventilation through activation of peripheral arterial chemoreceptors activation alone is not sufficient for reducing EPO levels and polycythemia. The better efficiency of female sex hormone treatment as compared to almitrine could be related either to the central effects of progesterone and estrogen and/or to the impact of these hormones on erythropoiesis at the kidney/bone marrow level.

Mechanisms underlying sex-related differences in adaptation to high altitude were investigated by assessing the turnover of dopamine and noradrenaline in structures of the chemoafferent pathway, i.e. carotid body and brainstem noradrenergic cell groups (A1, A5, A6, A2 to which chemosensory fibres project). The influence of gender was assessed in male and female rats reared at an altitude of 3600 m, whereas the influence of endogenous sex hormones was evaluated by castration. Haematocrit, red blood cell count and plasma erythropoietin levels were lower in females than in males (-5%, -15%, -53%, respectively). Dopamine and noradrenaline turnover were higher in female structures (carotid body: +51%; A2: +140%; A1: +54%; A5: +27%). Dopamine and noradrenaline turnover in carotid body and brainstem cell groups were differently affected by castration, i. e. enhanced by orchidectomy (carotid body: +134%; A2: +120%; A1: +69%; A5: +67%) but inhibited by ovariectomy (carotid body: -33%; A2: -92%). Orchidectomy elicited a reduction in haematocrit (-10%), haemoglobin concentration (-8%) and red blood cell count (-24%), whereas haematological status remained unaltered after ovariectomy. Therefore, both gender and endogenous sex steroids may control catecholamine activity differently in structures involved in the chemoafferent pathway, thus providing a neurochemical basis for sex-related differences in adaptation to hypoxia.

In sea-level natives, exposure to hypoxia for a few weeks is characterized by an increased dependence on blood glucose and a decreased reliance on lactate for energy metabolism during exercise. These metabolic adjustments have been attributed to behavioral changes in the sympathoadrenergic and pancreatic systems. The aim of this study was to test the hypothesis of a reduced sympathoadrenergic activation and subsequent metabolic changes when high-altitude natives are acutely exposed to normoxia. Young Andean natives performed incremental exercise to exhaustion during hypoxia (arterial PO2 55.1 +/- 1.1 Torr) or during acute normoxia (arterial PO2 78.7 +/- 1.7 Torr). As a whole, oxygen uptake was increased in normoxia compared with hypoxia during graded exercise. This finding is not related to a decrease in anaerobic metabolism but rather is interpreted as a consequence of a shift in substrate utilization during exercise (increased contribution of fat as assessed by a reduction in the respiratory exchange ratio). These metabolic changes are not accompanied by modifications of glucoregulatory hormones (catecholamines, insulin, and glucagon). In particular, the exercise-induced catecholamine secretion was similar in chronic hypoxia and acute normoxia. As a consequence, blood lactate accumulation during incremental exercise was similar in both conditions. It is concluded that high-altitude natives do not display any sign of a greater sympathoadrenergic activation during chronic hypoxia and that the exercise-induced hormonal changes remained unaffected by acute inhalation of a normoxic gas mixture.

We have previously observed that 11-year-old children of low socio-economic status (LSES) showed a delayed physical growth of approximately 2 years and developed lower normalized short-term power output than children of high socio-economic status (HSES) of the same age. In contrast, maximal oxygen uptake\((\dot VO_{2max} )\) per unit of fat free mass was no different in either group. The aim of this study was to evaluate the effect of anthropometric characteristics between HSES and LSES prepubertal children in aerobic and anaerobic performance. To compare children of the same body dimensions, 11-year-old boys (n = 30) and girls (n = 31) of LSES and 9-year-old boys (n = 21) and girls (n = 27) of HSES were studied. Anthropometric measurements,\(\dot VO_{2max} \) (direct test), maximal anaerobic power (Pmax, force-velocity test) and mean anaerobic power (\(\bar P\), Wingate test) were determined. In these children having the same body dimensions: mean\(\dot VO_{2max} \) were the same in LSES and HSES children [1.2 (SD 0.2)1-min−1];Pmax and\(\bar P\) were lower in LSES subjects [154.0 (SD 33.2) vs 174.6 (SD 38.4) W and 116.3 (SD 23.3) vs 128.2 (SD 28.0) W, respectively]; the linear relationships between\(\dot VO_{2max} \) and fat free mass were the same in LSES and HSES boys but, in the girls, the LSES group had lower values. For anaerobic performance, the relationships were significantly different: the slopes were the same but LSES values for the both sexes were lower. These results would suggest that factors other than differences in body dimensions alone were responsible for the lower performance of LSES girls and boys. Cultural factors and motor learning, structural and functional alterations of muscle induced by marginal malnutrition have been discussed.

Kayser, Bengt, Roland Favier, Guido Ferretti, Dominique Desplanches, Hilde Spielvogel, Harry Koubi, Brigitte Sempore, and Hans Hoppeler. Lactate and epinephrine during exercise in altitude natives. J. Appl. Physiol. 81(6): 2488–2494, 1996.—We tested the hypothesis that the reported low blood lactate accumulation ([La]) during exercise in altitude-native humans is refractory to hypoxia-normoxia transitions by investigating whether acute changes in inspired O2 fraction ([Formula: see text]) affect the [La] vs. power output (W˙) relationship or, alternatively, as reported for lowlanders, whether changes in [La] vs. W˙ on changes in[Formula: see text] are related to changes in blood epinephrine concentration ([Epi]). Altitude natives [ n = 8, age 24 ± 1 (SE) yr, body mass 62 ± 3 kg, height 167 ± 2 cm] in La Paz, Bolivia (3,600 m) performed incremental exercise with two legs and one leg in chronic hypoxia and acute normoxia (AN). Submaximal one- and two-leg O2 uptake (V˙o 2) vs.W˙ relationships were not altered by[Formula: see text]. AN increased two-leg peak V˙o 2 by 10% and peakW˙ by 7%. AN paradoxically decreased one-leg peak V˙o 2 by 7%, whereas peak W˙ remained the same. The [La] vs. W˙ relationships were similar to those reported in unacclimatized lowlanders. There was a shift to the right on AN, and maximum [La] was reduced by 7 and 8% for one- and two-leg exercises, respectively. [Epi] and [La] were tightly related (mean r = 0.81) independently of[Formula: see text]. Thus normoxia attenuated the increment in both [La] and [Epi] as a function of W˙, whereas the correlation between [La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitude natives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes in[Formula: see text] on [La] during exercise.