Interpopulational differences in progesterone levels during conception and implantation in humans

Abstract

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...

Reproduction and Growth

“…In any setting, accurate estimates of fetal loss are diffi cult to obtain, as the greatest risk for loss occurs in early pregnancy before a woman is aware of the conception. Using elevated human chorionic gonadotropin as a marker of implantation, the fetal loss rate in rural Aymara women was 30 %-very similar to the 31 % fetal loss rate reported among U.S. women using similar criteria [ 16 ]. Estimates of fetal loss based on reproductive histories among the Sherpa of Nepal and Tibetan women living at 3,000-4,000 m suggest approximately 10 % loss among recognized pregnancies [ 22 , 23 ], although this fi gure likely refl ects underreporting.…”

“…This continuum likely relates to differences in nutrition and physical demands during childhood development, as it correlates with body size [ 14 , 15 ]. Despite having lower progesterone levels during the fertile period, rural Bolivian women conceived and carried pregnancies to full term [ 16 ]. Early pregnancy loss in rural Bolivian women was associated with higher follicular progesterone and low luteal/ follicular progesterone ratios [ 17 ].…”

A prospective study of early pregnancy loss in humans

“…Data collection was conducted within the framework of Project REPA (Reproduction and Ecology in Provincía Aroma), a multidisciplinary longitudinal study of reproductive functioning and health among rural Aymara families indigenous to the Bolivian altiplano (32). All study protocols were approved by the Institutional Review Board, University of California, Riverside.…”

“…The data collection protocol has been previously described (32). In brief, throughout participation, menstruating women (n ϭ 191) were visited every other day to record menstrual status and collect a 5-mL saliva sample.…”

Impact of gene polymorphisms of gonadotropins and their receptors on human reproductive success

“…Hyperandrogenism, metabolic syndrome, insulin resistance, and anovulation are some of the main clinical aspects of PCOS, which may be the result of endocrine adaptation to ancestral environmental conditions (Corbett & Morin-Papunen 2013, Casarini & Brigante 2014. Several studies searched evolutionary explanations for the origin of PCOS, suggesting that the energy saving resulting from less-ovulatory reproductive systems and insulin resistant phenotypes may be advantageous during seasons of food shortage or high energy demand, when indeed the anovulation risk increases (Vitzthum et al 2004, Vitzthum 2009, Corbett & Morin-Papunen 2013. However, theories supporting natural selection of PCOS phenotypes were downsized in favor of genetic drift; this issue is still debated and needs further investigation (Casarini & Brigante 2014).…”