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: Nth 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. © 1999 Wiley‐Liss, Inc.

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.

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% O2 only L showed a significant increase. During exercise in air, arterial PCO2 was 8 Torr lower in L than in N (P < 0.001), yet PO2 was the same such that, at maximal O2 uptake, alveolar-arterial PO2 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 PCO2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial PO2 despite 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.

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.

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 crosssectional 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 Ϸ71% that of the women from Chicago. In conception cycles, progesterone levels in Bolivian women during the periovulatory period were Ϸ63%, and during the peri-implantation period were Ϸ50%, 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.I n an evaluation of demographic data from populations worldwide, Bongaarts (1) concluded that, except in cases of famine, nutritional factors play a relatively minor role in determining human fecundity (capacity to conceive) or fertility (number of live births). Despite characteristically marginal nutritional status and the demands of arduous activities, women in less developed countries often average seven to eight pregnancies, some having 12 or more during a lifetime. Differences among populations, or reductions from a theoretical maximum, appear fully attributable to a limited set of behavioral and physiological proximate fertility determinants apparently little affected by nutritional factors. If neither fecundity nor fertility is thus significantly influenced, neither is fecundability (the monthly probability of conception). Yet clinical studies of women from the United States indicate a sensitivity of ovarian function to both relatively low energy intake and͞or high energy expenditure. The most extreme response, failure to ovulate, may occur in the face of only moderate energetic stress (2-4) and, of course, reduces fecundity and fecundability to 0. Short of anovulation, milder disruptions of ovarian function may also reduce fecundability. Why should o...