Epidemiological transitions, reproductive health, and the Flexible Response Model

Economics and Human Biology 1 (2003) 223–242

Epidemiological transitions, reproductive health, and the Flexible Response Model Virginia J. Vitzthum a,1 , Hilde Spielvogel b,∗ a

National Science Foundation, 4201 Wilson Blvd. (995.15), Arlington, VA 22230, USA b Instituto Boliviano de Biolog´ıa de Altura, Casilla 641, La Paz, Bolivia

Received 17 March 2003; received in revised form 17 March 2003; accepted 17 March 2003

Abstract In concert with improving standards of living since the mid-19th century, chronic and noninfectious 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 Provinc´ıa 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. © 2003 Elsevier Science B.V. All rights reserved. JEL classification: I1 Keywords: Reproductive health; Women’s health; Bolivia

1. Introduction Epidemiologic Transition Theory as formulated by Omran (1971, 1983) is based on the observation that coincident with generally rising standards of living in western Europe since the mid-19th century, chronic and non-infectious diseases replaced infectious diseases as the major causes of morbidity and mortality. This connection between infectious diseases ∗ Corresponding author. Tel.: +591-2-279-3734; fax: +591-2-279-3734. E-mail addresses: [email protected] (V.J. Vitzthum), [email protected] (H. Spielvogel). 1 Tel.: +1-703-292-7318; fax: +1-703-292-9068.

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and socio-economic conditions has long been at the foundation of efforts to improve health through economic development in less developed countries. Analogous to this approach, those individuals and organizations concerned principally with reproductive health have called for economic development, among other strategies, as a means to achieve their goals. There is compelling evidence that various features of developed economies—safe sewage disposal and clean water supplies, access to health care, increased food security and quality, lower illiteracy rate and greater economic independence of women—can all contribute to a general improvement in women’s reproductive health. Globally, two of the greatest threats to the reproductive health of adult women are the mortality and morbidity associated with pregnancy and delivery, and cancers of the breast and reproductive system. The prevalence of these causes of death appear to accord with the lineal progression of mortality stages suggested by Omran: the highest maternal mortality is found in the poorest countries, the highest rates of breast cancer in the more developed countries. Thus, it might be anticipated that as economic conditions improve, maternal mortality will decrease. Likewise, it may be expected that breast cancer would not rise in the absence of significant economic development. A closer scrutiny of the evidence, however, finds a much more complicated pattern. In more developed countries, incidence of breast cancer has risen far higher than can be explained by better screening, longer life-span, or improving economic standards. In many less developed countries, the risk of maternal mortality remains egregiously high despite better economic indicators. Disproportionate to any economic gains that may have occurred, chronic and non-infectious diseases are a rapidly growing liability even as infectious diseases remain a major obstacle to health (Osmani and Sen, 2003). We begin with a brief review of the literature on epidemiological transition and reproductive health followed by an examination of contemporary patterns and etiologies of maternal mortality and breast cancer. The evidence suggests that a linear progressive model does not adequately describe these patterns of morbidity or mortality. Instead, we propose incorporating an evolutionary perspective into understanding variations in women’s reproductive functioning and health. The Flexible Response Model, rooted in life history theory and evolutionary biology, was developed to explain the evolution and current functioning of the human reproductive system (Vitzthum, 1990, 1997, 2001a,b). The Flexible Response Model is briefly described and then tested against data from Project Reproduction and Ecology in Provinc´ıa Aroma (REPA), a longitudinal study of Bolivian women. We conclude by discussing how these findings can contribute to improving women’s reproductive health.

2. Epidemiological transitions Omran (1971) formulated a descriptive framework, “the epidemiologic transition”, to refer to an historical shift in the principal determinants of human mortality. Based on demographic trends in western Europe, he conceived of three periods: (1) the age of pestilence and famine, during which high mortality levels result primarily from infectious diseases and malnutrition; (2) the age of receding pandemics, during which falling mortality levels are attributable to significant reductions in infectious diseases accompanied by slowly rising

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rates of degenerative diseases; and (3) the age of degenerative and man-made diseases, distinguished by low levels of infectious disease and low mortality until aged. The broad strokes and limited geographic focus of this framework naturally elicited many critiques and addenda. From a prehistoric perspective, it is evident that the transition described by Omran is but one of several. Prior to the invention of agriculture, some 10,000 years ago, low-density foraging (gathering and hunting) bands of humans could not have supported the bulk of infectious diseases common to clustered sedentary populations, particularly those with domesticated animals (Burnet, 1962; Ewald, 1994). Livingstone’s (1958) reconstruction of the rise of malaria and sickle cell anemia coincident with increased mosquito breeding sites in the standing water that accompanies agriculture exemplifies this first epidemiological transition. However, many thousands of years remained before the conditions of sufficient population density, urbanization, social stratification, unequal control of resources, and travel much beyond one’s birthplace would herald an age of pestilence and famine, a second epidemiological shift. Contemporary mortality trends have prompted the conception of two more epidemiological stages subsequent to those offered by Omran: the age of delayed degenerative diseases, in which life expectancy increases but morbidity and mental illness also increase (Olshansky and Ault, 1986); and the age of emergent and re-emergent infections (Olshansky et al., 1997; Small-Raynor and Phillips, 1999). However, transitions may not proceed either sequentially or similarly among different populations or across all strata of a socio-economically heterogeneous population (Small-Raynor and Phillips, 1999; Waters, 2001). Questions have also been raised about the utility of all-cause mortality levels or any single cause of mortality as markers of “epidemiological” transitions (Fathalla, 1992; Mackenbach, 1994). Thus, intending to encapsulate the cultural, social, and behavioral determinants of well-being, some prefer the concept of “health transition” (Caldwell et al., 1990). Whatever its limitations, the construct of epidemiological (or health) transitions and their causes are a prominent framework in demography and public health (Barros et al., 2001; Caldwell et al., 1990; Jamison et al., 1993). Especially in international development efforts, transition theory has guided the approaches of some “health for all” policies (WHO, 1998). In the classical model (derived from western Europe), Omran (1971, 1983) attributed the transition to a rising standard of living brought about by social progress. Hence, economic development, in addition to widespread immunization and sanitation programs, has been seen as key to bringing poorer countries through the epidemiological transition. Relatively little thought was given to the trade-offs in well-being that might be incurred, to what factors other than socio-economic conditions might be important, or to the unique health needs of women.

3. Reproductive health: more than mom Broad familiarity with the concept of reproductive health is but a decade old, having been proposed by Fathalla (1992) as “A condition in which the reproductive process is accomplished in a state of complete physical, mental and social well-being and is not merely the absence of disease or disorders of the reproductive process.” While men’s reproductive

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health is implicitly included, it is the reproductive health of women that has received the greatest attention. This emphasis is perhaps not unreasonable given that pregnancy, but one aspect of the reproductive process, is associated with at least 500,000 female deaths per year, and pregnancy-related morbidity is estimated to affect 5 million additional women annually. The focus on women’s reproductive function, if not on women themselves, began and rapidly escalated in the 1960s with an urgent call for slower population growth (Ehrlich, 1968). Between 1930 and 1960 the world had grown from 2 to 3 billion people; by 1975 it had reached 4 billion. The neo-Malthusian perspective argued that natural checks on human growth had been undermined by modern medical and social progress, and certain ecological disaster could only be averted by drastic measures. “Population control” acquired a pejorative reputation, however, and hence “family planning” became the watchword of the 1970s and thereafter, virtually all efforts being directed towards women. Safe Motherhood/Maternal-Child-Health programs expanded during the 1980s, though by the end of the decade more than one author had questioned whether sufficient attention had been paid to the maternal aspects of the program (AbouZahr and Wardlaw, 2001; Freedman and Maine, 1993; Maine and Rosenfield, 1999). International efforts were coordinated in part by the United Nations’ International Conferences on Population and Development (ICPD) in 1974 in Bucharest, Romania; in 1984 in Mexico City; and in 1994 in Cairo, Egypt. The Bucharest meeting witnessed little advancement in population policy. The proposal by less developed countries and communist-bloc countries of a “new international economic order” (from which slower growth rates would purportedly emerge) squared-off against the interest of industrialized nations to reduce global population growth through direct fertility-reducing interventions. Mexico City (1984) witnessed a reversal of ideological stances. Many less developed countries had begun family planning programs in recognition of the negative economic consequences of a burgeoning population, but the Reagan administration issued the “Mexico City gag rule” prohibiting the use of USAID (United States Agency for International Development) funds for any program that provided or referred for abortion. The Cairo meeting (1994) was the watershed that brought reproductive health into the international arena of population debates. The unprecedented attendance by large numbers of women, most representing women’s non-governmental organizations, shifted discussions from principally governmental concerns with fertility targets to those of women, their health, and the health of their families. Noted one journalist: “Where else has the fundamental condition of all women, whatever their status or the state of their personal freedom, been so intensely debated, or seen to be so relevant to the next century?” In the Cairo Program of Action, women’s rights to economic and social equity were recognized to be integral to the achievement of health for all women, and family planning was seen as but one part of a comprehensive array of reproductive health services. Yet, distinguishing reproductive health from the spheres of maternal and women’s health is conceptually and practically difficult (Freedman and Maine, 1993; Kane, 2000; Koblinsky et al., 1993). Fathalla’s (1992) formulation of reproductive health encompassed “the reproductive process . . . carried to a successful outcome through infant and child survival, growth, and healthy development.” That is, infant, child and maternal health were subsumed within reproductive health. The Cairo 1994 ICPD definition is broader yet:

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“Reproductive health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity, in all matters relating to the reproductive system and to its functions and processes. Reproductive health therefore implies that people are able to have a satisfying and safe sex life, and that they have the capability to reproduce and the freedom to decide if, when and how to do so . . . . It also includes sexual health . . . and not merely counseling and care related to reproduction and sexually transmitted diseases” (United Nations, 1994, paragraph 7.2). While potentially all encompassing, the Cairo Program of Action further specified that the principal foci were a safe and satisfying sex life with the capacity to reproduce and the freedom to make reproductive decisions including access to lawful fertility regulation methods and health services for pregnancy and childbirth, emphases close to those proposed by Fathalla. Subsequently, several authors have broadened reproductive health to the full potential of the Cairo definition and even further (Freedman and Maine, 1993; Kane, 2000). Yet, it is clear that very few countries have the resources to implement such a comprehensive program, and priorities must be set. Two particularly compelling challenges to women’s reproductive health are deaths associated with pregnancy and birth, and breast cancer. 3.1. Maternal mortality Among health indicators, there is no greater disparity between more and less developed countries than those reflecting maternal mortality. The estimated number of maternal deaths worldwide in 1995 is 515,000 of which 99% occurred in less developed countries. The maternal mortality ratio (number of mothers’ deaths/100,000 live births) is estimated at 11 in North America but rises to 1000 in the least developed countries. The lifetime risk, a measure of the probabilities of pregnancy and death from maternal causes, is 1 in 11 in eastern Africa compared to only 1 in 5000 in southern Europe. Among women aged 15–44 years, maternal causes are the leading contributors (14.5%) to the global disability adjusted life years (DALYs).2 Unipolar major depression (13.7%) is second; all other categories of diseases and injuries each contribute <6% of the total. In other words, every minute of every day a woman dies as a result of complications during pregnancy and childbirth. Particularly tragic is that the overwhelming majority of these deaths are avoidable. Maternal death is defined as that occurring while pregnant or within 42 days of the end of pregnancy from any cause related to or aggravated by the pregnancy or its management. Indirect obstetric deaths (20% of global total) result from previously existing diseases or from diseases arising during pregnancy that were aggravated by the physiological effects of pregnancy (e.g. malaria, anemia, HIV/AIDS). Leading causes of direct obstetric deaths are hemorrhage (25% of global total), sepsis (15%), unsafe abortion (13%), hypertensive disorders (i.e. those characterized by high blood pressure (12%), and obstructed labor (8%). The medical technology to prevent these deaths is well established and a high Gross National 2 DALY is a measure of the years of life lost to premature death and years of life lived with disability; developed by WHO, the World Bank and the Harvard School of Public Health to characterize global levels of mortality and morbidity.

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Product is not prerequisite to the implementation of successful maternal health programs as evinced by interventions in Sri Lanka, Cuba, China, and Malaysia. Yet, little if any progress has been made in reducing global levels of maternal mortality since the 1987 inauguration of the United Nations’ Safe Motherhood Initiative. Social and cultural barriers have proven to be impediments perhaps greater than technological or economic barriers. Inequity in women’s status negatively impacts the allocation of resources to women’s health regardless of the level of economic development, hobbles women’s access to and management of resources, and imperils the fundamental right to regulate one’s own reproductive function. Imbedded within nearly every statement or program addressing maternal mortality is the recognition that the prevention of unwanted pregnancies is one major path to its reduction (hence the Vatican’s opposition at the Cairo 1994 ICPD to “Safe Motherhood,” “reproductive health,” “reproductive rights,” and “unsafe abortion” as well as “family planning”). Annually, more than 60,000 maternal deaths from unsafe abortion (and a far greater morbidity toll) would be averted by access to safe effective contraception. Moreover, the lifetime risk of maternal mortality (reflecting the probabilities of pregnancy and dying from pregnancy) from all-causes could be drastically reduced, even in the face of no change in unconscionably high maternal mortality ratios, by fulfilling the unmet need for contraception. Of women who have expressed a desire to stop bearing children, only 25–60% (varying among less developed countries) are using contraception, leaving as many as 100 million women worldwide at risk of unwanted pregnancy. The many causes of the unmet need reflect the familiar cultural, social, and economic constraints that impact women’s reproductive health negatively in general. However, even if effective hormonal contraception is available and initiated, there are high rates of discontinuance in many developing countries (Vitzthum and Ringheim, 2000), potentially leading to unwanted pregnancies and unsafe abortion. Among the reasons given for suspension, women across a wide range of cultural, economic, and political conditions often report concerns with side-effects (Fig. 1). Yet, among contraceptive specialists, discontinuance has been explained most often as a lack of knowledge on the part of poorly educated women, itself the result of low economic development. The usual intervention is to increase the information provided at clinics and to counsel women that the side-effects are manageable, or even imagined. The discordance between women’s reasons and professionals’ explanations suggests the principal cause of high rates of discontinuance has yet to be recognized. This point is further explored below. 3.2. Breast cancer The number of women diagnosed with breast cancer in 2002 is estimated at 1.2 million. It is the most common cause of cancer (excluding non-melanoma skin cancers) and the second leading cause of cancer deaths (after lung cancer) among women, accounting for 13.5% of women’s cancer disability adjusted life years and more than half of the reproductive-cancer DALYs (1990 estimates). The incidence rate is about three times greater in more developed countries than less developed countries (63 versus 23 per 100,000 women, age-standardized rates); the mortality rate is twice as high (19 versus 9 per 100,000 women, age-standardized rates) reflecting the superior care in more developed countries.

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Fig. 1. Percentage of women in selected Latin American countries who discontinued oral contraceptives within 12 months of starting, and those reporting “side-effects/health concerns” as the primary reason for doing so. Source: Vitzthum and Ringheim (2000).

Worldwide, age-standardized breast cancer rates have increased by 26% since 1980; 40% of new cases occur in developing countries. While some of the increase is reasonably attributable to improved diagnosis and longer life-span, the appearance of cancer at younger ages, particularly more virulent forms, suggests that this may not be the entire explanation. Yet, despite the substantial mortality and even greater morbidity attributable to breast cancer, the disease receives relatively scant attention in international forums on women’s health. This failure is a combined legacy of the tendency to regard women principally as mothers, disregarding them once the reproductive years have passed, and the erroneous notion that breast cancer is a disease of the aged. In fact, breast cancer is the leading cause of death for women 40–55 years old in the United States. “Lifestyle factors” are held to be the principal determinants of breast cancer, though disappointingly little is understood of its etiology (cause or origin). Cross-national and migrant studies suggest that dietary factors may be significant but case-control studies have not confirmed this hypothesis consistently (Jamison et al., 1993). In 1971, Fatalla proposed that cancers of the reproductive system result from the “incessant ovulation” associated with modern reproductive patterns, specifically: a longer reproductive life-span, a longer lag from menarche to first birth, fewer births, and less breastfeeding. Eaton et al. (1994) compared the reproductive patterns of foraging peoples, living a life style resembling that of pre-agriculture humans, with those of contemporary US women and concluded that over the course of a life time the latter would average three times more ovarian cycles (160 versus 450). Several epidemiological studies have found an association between risk of breast cancer and biological and behavioral factors that increase the number of cycles, also lending support to Fatalla’s hypothesis of the impact of prolific cycling.

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4. An epidemiological transition in reproductive health? Maternal mortality and breast cancer are not only two of the greater challenges to women’s health, but at first inspection their distribution would appear to exemplify Omran’s formulation of the epidemiological transition from an age dominated by infectious diseases and malnutrition to one dominated by degenerative diseases. Omran (1971, 1983) specifically noted that maternal mortality is disproportionately lowered by the epidemiological transition. Yet, the major declines in maternal mortality ratios occurred in more developed countries much more recently than the general mortality declines of 19th century Europe that are the foundation of Omran’s framework (Loudon, 2000). Moreover, the maternal mortality ratio declines are principally attributable to advances in medical practices and technology, and more recently to the legal status of abortion, than to socio-economic progress. Maternal mortality ratios remained high in industrialized countries (e.g. 300/100,000 in Sweden) until the mid-1930s when sulfonamides, effective against the Streptococcus strains that caused sepsis, were introduced. Subsequent advances included penicillin, blood transfusions, and better obstetric training and practices. The rate of decline was similar in all more developed countries and reached approximately similar levels (about 60/100,000 live births) by 1960 (Loudon, 2000). In the US, subsequent to the pivotal legalization of abortion in Roe versus Wade (Supreme Court decision in 1974), mortality attributable to induced abortion declined by 89% in the 7-year period from 1975 to 1982 (Rosenberg and Rosenthal, 1987). In the absence of these obstetric advancements, low maternal mortality ratio is not automatically conferred with relatively high economic status as evidenced by a study of the Faith Assembly, a US religious group that rejects all biomedicine including midwives, relying instead upon prayer (Kaunitz et al., 1984). Though middle-class (well-nourished, employed, white) the maternal mortality ratio in this group was 872/100,000 (due to hemorrhage and sepsis) compared with 9/100,000 in the state of Indiana at the time. Nor, as demonstrated by the efforts in less developed countries noted earlier, is a high level of economic development necessary to successful maternal health programs. In fact, maternal mortality ratio even declined in the 1930s during the great depression in the US (Loudon, 2000). Based on an extensive historical analysis of maternal mortality, Loudon (2000) concluded, “High and low rates of maternal mortality have never corresponded to changes in economic conditions.” It is less clear whether or not breast cancer rates are necessarily associated with economic conditions. While the highest rates of breast cancer are found in more developed countries, rates are increasing in less developed countries even without significant economic change. This pattern has been attributed to a small upper and middle-class increasingly experiencing the diseases of modernization even as the majority of the population suffers from “pre-transition” maladies. Inherent within this explanation is the unexplored assumption that breast cancer is a “degenerative or man-made disease” that inevitably accompanies the adoption of a modern life style and the reduction of death due to infectious disease. While not dismissing the possible effects of diet and other lifestyle factors, the prolific ovarian cycling hypothesis places reproductive patterns rather than age per se at the heart of breast cancer etiology. For women in some more developed countries, certain features

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of contemporary reproductive patterns (e.g. late age at marriage) appear to have begun long before the economic and mortality shifts of the 19th century, while others appear to reasonably correspond to 19th and 20th century changes in the standard of living (e.g. the secular trend in decreasing age at puberty), and still others are very recent (e.g. the widespread adoption of contraception). Hence, economic conditions are but one of several factors that may modify cycling frequency and thereby, the risk of breast cancer. The evidence discussed above suggests that “epidemiologic transition theory” is neither a useful framework for describing the variation either over time or among countries in two principal aspects of women’s reproductive health, nor a productive approach for understanding the role that economic factors play in those patterns. Rising economic indicators have not necessarily promoted lower maternal mortality, and programs to reduce maternal mortality have been successful without economic development. Nor does the level of economic development explain discontinuation rates of hormonal contraception, one of the most successful strategies for reducing the lifetime risk of maternal mortality. Globally, the incidences of cancers of the breast and of the reproductive track have risen far higher than can be explained by a rising standard of living. Global and historical experiences suggest that lowering maternal mortality requires, regardless of economic conditions, specific programs targeting obstetric practices. Lifetime risk of maternal mortality is also achieved through preventing unwanted pregnancies. However, women need to be offered acceptable as well as efficacious hormonal contraceptives. Moreover, fertility reduction can lead to increased cycling frequency and possibly increased risk of breast cancer regardless of economic status. Thus, might it be the case that economics have little to do with reproductive health, at least with respect to maternal mortality and breast cancer? To address this question, we propose first viewing reproductive functioning from an evolutionary perspective.

5. Bringing evolutionary biology to women’s health To gain better insight into the determinants of women’s health, we propose incorporating the theory and evidence from evolutionary biology into studies of the relationship between economics and human health, particularly women’s reproductive health. This approach has come to be known as evolutionary medicine (Trevathan et al., 1999), and has proved useful in understanding the complex relationships between the human organism and its varied environments that result in illness. It is a fundamental ecological principal that organisms must partition energy to growth, maintenance/survival, and reproduction over the course of a life-span. The myriad ways in which this goal is addressed are referred to as life history strategies, the varying success of which is dictated by the process of natural selection. Successful strategies are those that contribute proportionally more offspring to the next generation relative to other strategies, during the span of the organism’s life (lifetime reproductive success). The Flexible Response Model (Vitzthum, 1990, 1997, 2001a,b) integrates what is currently known of human variation, developmental biology, and life history theory to explain the evolution of human reproductive strategies and contemporary variation in women’s reproductive functioning. Briefly, organisms may have a short or extended developmental

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period, but reproduction is usually not undertaken during this life stage. Adulthood is typically defined by reproductive effort, which may be undertaken in a single burst or parceled over time, and can involve considerable risk to survival. Because of this risk, and the risk of current reproductive investment precluding future reproduction even if surviving, in the context of a current opportunity to reproduce an organism must “decide” whether to do so. If current effort does not risk future opportunities, attempting reproduction is always advantageous. If risk is incurred, three probabilities underlie the decision to reproduce: (1) the probability of successful reproduction (conception and live birth) under the current set of conditions, (2) the probability of conditions changing for better or worse within some finite period of time, (3) the probability of a change in reproductive capacity. Thus, for example, under short-term sub-optimal conditions it is better (i.e. increases lifetime reproductive success) to delay reproductive effort. However, if relatively poor conditions persist then delaying incurs the risk of never investing, ultimately the poorest strategy. Therefore, if the probability of successful reproduction under these sub-optimal conditions is greater than zero, it is better to adjust functioning and attempt to reproduce than to forego reproductive effort entirely.3 An organism’s physiological recognition and evaluation of environmental cues is dependent, in part, upon conditions experienced during the developmental period. The relative optimality of current ecological conditions is not measured against some imaginable standard of ideal conditions, but rather against the best conditions that typically obtain in the local context of that organism. It is essential to comprehend that the fitness of a phenotype4 is not inherent but varies according to the environment within which selection among phenotypes is occurring. The failure to recognize this principal has led some (Ellison, 2001) to argue that natural selection always favors reduced reproductive effort in the face of less than ideal conditions. In addition to theoretical arguments for the converse, the empirical evidence discussed below suggests otherwise. According to the Flexible Response Model, natural selection favors a reproductive system that responds flexibly to current ecological circumstances, predicated upon developmental experiences. In humans, it is now well established that many aspects of adult morphology and function reflect exposure to varying conditions experienced during a characteristically lengthy development. The Flexible Response Model also implies that selection favors a phenotype that adjusts to a persistent sub-optimal context. Again, there are many examples of such “acclimatization” in humans, which returns an organism to homeostasis (a state of normal functioning) in the presence of an ongoing stressor. The Flexible Response Model 3 The Flexible Response Model can be likened to a poker game with a finite number of hands. If the dealer calls a game you do not like, you bow out and wait till the next dealer’s call, hoping it will be better (zero-investment delayers). You have lost an opportunity to win, but you still have your stake for the next game. But if the next call is equally or more distasteful, your gambit was wasted; if you never play, in the reproductive game you lose. Clearly, it’s worth the ante to get in the game. Yet, if you bet your entire stake (obligates) and lose, you can’t play the next hand. Over the long haul, the one who plays the game, but adjusts her bets to the cards, is the winner. In the language of life history theory, such variability in reproductive investment is termed “bet-hedging,” a buffer in the face of environmental variation (Seger and Brockmann, 1987; Chisholm, 1993). 4 Fitness is a measure of the relative advantage of one phenotype over another; phenotype is the observable outcome (e.g. stature, hormone level, life history strategy) of the interaction between an organism’s genes (genotype) and its environment.

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predicts that: (1) there is substantial inter-individual and inter-populational non-pathological variation in reproductive functioning, and (2) this variation reflects both short-term (acute) and long-term (chronic) conditions. The next section discusses research findings that support the Flexible Response Model, followed by a consideration of the implications of the model for improving women’s reproductive health and understanding the biological mechanisms that link economics and women’s health.

6. Natural variation in women’s reproductive function At the heart of an evolutionary analysis of any aspect of biology is the recognition that variation, a result of the interaction of genetic and environmental variation, is inevitable and potentially adaptive. With regard to women’s reproductive functioning, there has been remarkably little appreciation of this characteristic of all organisms. To better understand the extent and causes of this variation, Project Reproduction and Ecology in Provinc´ıa Aroma— a multidisciplinary, longitudinal study of reproductive functioning and health—was undertaken among rural Aymara families indigenous to the Bolivian altiplano. Preliminary studies began in 1989, followed by more than 2 years of continuous fieldwork from 1995 to 1997 and additional data collection through 1999. Participants (n = 316 women of reproductive age) were recruited from 30 agro-pastoral communities located about half-way between La Paz and Oruro (Fig. 2). Comparative data were also collected from urban samples of better-off and poorer women of reproductive age residing in La Paz (n = 61).

Fig. 2. Map of Bolivia. URL: http://www.lib.utexas.edu/maps/cia02/bolivia sm02.gif.

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6.1. Inter- and intra-populational variation in menses duration Perhaps the most salient evidence of an adult women’s reproductive status is menstrual bleeding. This discharge of the vascularized5 uterine wall, regulated by reproductive steroids, occurs in the absence of conception and/or implantation during the current ovarian cycle. Project REPA collected data on ovarian functioning from 191 rural Aymara women (93 lactating/menstruating; 98 non-lactating/menstruating) including menses duration, one measure of the magnitude of uterine vascularization. As predicted by the Flexible Response Model, an analysis (Vitzthum et al., 2001) of published comparable data on menses duration found substantial natural variation in ovarian function among populations. The range is nearly two-fold, from 3.5 days in Bolivian Aymara women to 6 days in US women. Very little is known, however, of the reasons for this variation. The Flexible Response Model proposes that current ecological conditions (including those that influence a women’s nutritional status) affect the magnitude of uterine wall development, estimated to require about 10% additional energy expenditure, and therefore predicts that a woman’s menses length will be positively correlated with her current fatness level. Frisch (Frisch and McArthur, 1974; Frisch, 2002) is well known for suggesting the existence of a fatness threshold below which ovulation would not occur. Her recognition of the influence of nutritional status on reproduction in humans helped lay the foundation for understanding human fertility patterns in an evolutionary context. However, the Flexible Response Model differs from the Critical Fat Hypothesis developed by Frisch, in that no species-specific fatness threshold is predicted. Rather, the relationship between nutritional status and ovarian function is hypothesized to be dependent upon the individual’s own developmental experiences in the context of her specific environment and population. To test the hypothesis that menses length and nutritional status are correlated among rural Bolivian Aymara women, anthropometric indicators were collected by the same observer (VJV) according to standard procedures (Lohman et al., 1988). Compared to lactating women, non-lactating women were significantly older, had earlier first births, were taller, weighed more, had larger skin circumferences, and larger skinfold measurements (Table 1), therefore analyses were conducted separately on these two samples (Miller et al., 2002). For each sample of women, principal components analysis extracted two anthropometric factors, the first reflecting body fat levels based on skinfolds and weight, and the second a proxy for the fluid retention associated with the luteal (post-ovulatory) phase of the menstrual cycle (Table 2). In both lactating and non-lactating samples, there are no significant correlations between menses duration and age, years of education, age at menarche, age at first birth, number of births, days postpartum, cycle length, or the water-retention-factor. However, as predicted by the Flexible Response Model, linear regression of menses length on the fatness-factor was significant in lactating women (r = 0.324, r 2 = 0.105, P = 0.005, one-sided); those with fatness scores > median fatness have significantly longer menses (mean = 3.81 days, median = 4 days) than those with fatness scores < median fatness (mean = 3.34 days, median = 3 days). The difference between these two groups in mean menses length is 0.47

5

Containing recently formed blood vessels.

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Table 1 Anthropometrics in menstruating/lactating and menstruating/non-lactating rural Aymara women

Height (cm) Weight (kg) Arm Circumference (cm) Calf circumference (cm) Thigh circumference (cm) Subscapular skinfold (mm) Suprailiac skinfold (mm) Triceps skinfold (mm) Biceps skinfold (mm) Calf skinfold (mm) Thigh skinfold (mm) Hemoglobin (g/dl)

Menstruating/lactating (n = 70)

Menstruating/non-lactating (n = 74)

Mean

S.D.

Mean

S.D.

148.7 51.6 25.3 31.0 49.5 14.2 16.3 13.1 5.3 10.4 16.6 15.29

4.2 6.5 2.2 2.0 3.5 5.3 7.5 3.8 1.7 2.5 4.9 1.65

150.8 54.5 26.6 32.0 51.1 16.5 20.6 17.2 6.9 13.7 19.6 15.47

4.6 6.6 2.2 1.8 3.5 5.8 9.5 9.5 2.7 5.3 5.7 1.97

days, approximately 13% of the sample mean menses length. No significant relationship between fatness level and menses duration was found, however, in non-lactating women (Miller et al., 2002). 6.2. Intra-populational variation in rates of anovulation and progesterone levels To test hypotheses of the Flexible Response Model regarding the effects of acute and chronic stress on reproductive function, saliva samples were collected from poorer and Table 2 Factors extracted by principal components analyses Component Menstruating/lactating 1a

Component matrix Subscapular SF Suprailiac SF Triceps SF Biceps SF Calf SF Thigh SF Weight Hemoglobin

0.912 0.884 0.854 0.840 0.811 0.848 0.810 0.156

Initial eigenvalues % of variance

5.105 63.814

Total variance

77.303

a b

Fatness. Water.

2b 0.136 −8.479E−02 0.187 −0.224 −0.193 −6.995E−02 7.489E−02 0.959 1.079 13.489

Menstruating/non-lactating 1a 0.825 0.895 0.651 0.888 0.702 0.853 0.845 0.218 4.678 58.475 70.811

2b 4.146E−02 9.788E−02 −0.136 −4.123E−02 −0.152 −6.966E−02 −4.760E−02 0.962 0.987 12.336

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better-off La Paz women, and later assayed for progesterone. The better-off women were all professionals and/or university students. The majority of the poorer women supported their households through manual labor including clearing large stones or laying cobbles for road building, hauling crops and other products for market, hand laundry and housecleaning. Those without any current monetary income (only working in the household) typically also engaged in manual labor including hauling water and fuel, and occasionally traded manual labor for food. It may be assumed that the majority of these women were raised in conditions roughly similar to those of their adult economic status. Hence, poorer women probably experienced relatively poorer conditions during their childhood. In addition, these data were collected during the Bolivian winter months, a period when some of the very poorest urban dwellers can experience a temporary loss of food supplies from relatives on farms. In contrast, the better-off women did not suffer the acute stress of seasonal variation in food supply. Coinciding with mid-follicular (days 7–9) and mid-luteal (days 21–23) phases, standard anthropometric indicators (Lohman et al., 1988) were collected by a single observer (HS). For comparison, a sample of Chicago women attempting to conceive provided daily salivary samples which were subsequently assayed for progesterone in the same laboratory according to identical protocols (Lu et al., 1999). The Flexible Response Model predicts that individuals experiencing acute stress should have a higher rate of anovulation6 than those not under stress. Thus, Chicago women and the better-off Bolivian women, none of whom were experiencing energy constraints at the time of data collection, should have comparable rates of anovulation. In contrast, the poorer Bolivian women, some of whom may have been experiencing seasonal food shortages, are expected to have a relatively higher rate of anovulation than either of the former two samples. As predicted, anovulatory rates did not differ (χ 2 = 0.104, two-sided P = 0.747) between Chicago women (9%) and better-off (12%) La Paz women but were significantly higher (χ 2 = 10.97, P = 0.001) in poorer (55%) than better-off La Paz women (Vitzthum et al., 2002). Rather than pathological, the reduction in fecundity evidenced by the high rate of anovulation in the poorer women is more appropriately viewed as an adaptive response to short-term (acute) resource limitations. The Flexible Response Model also predicts that, reflecting adaptation to long-term conditions, reproductive steroid levels in ovulatory cycles should be lower in women who experienced relatively greater stress during the developmental period of their lives. Chicago women, better-off Bolivian women, and poorer Bolivian women probably fall along a gradient from better to worse childhood conditions. As predicted, in samples comprising only ovulatory cycles, mean-peak-P varied significantly (Fig. 3), being greatest for Chicago women (330 pmol/l) and lowest in the poorer La Paz women (208 pmol/l), better-off La Paz women falling midway (232 pmol/l) (Vitzthum et al., 2002). To test whether the effects of chronic childhood conditions explain variation among women as well as among populations, an individual-level measure of childhood conditions is needed. There is ample evidence that chronic nutritional deprivation during the growth

6

Defined as the proportion of cycles having mean-peak-P (an estimate of the average of the observed progesterone during the mid-luteal phase) <110 pmol/l.

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Fig. 3. Progesterone levels (y-axis, units are pmol/l) in Chicago and Bolivia samples. Profiles for individual cycles are aligned on the first day of the subsequent cycle (day 0) and reverse numbered (x-axis). Source: Vitzthum et al. (2002).

period results in relatively shorter adult stature (Bogin, 1999; Komlos and Baten, 1998). Therefore, progesterone levels in ovulatory cycles should be positively correlated with body-size. To test this hypothesis, principal components analyses were used to reduce the progesterone indices to a single factor (“P-level”) representing variation in overall

Fig. 4. Correlation of body-size (x-axis, a principal component score derived from individual anthropometrics) and P-level (y-axis, a principal component score derived from individual progesterone levels). Note: filled circles pertain to poorer Bolivian women, open circles to better-off Bolivian women.

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progesterone level and accounting for 73% of the total variance in progesterone. From the anthropometric evidence, two factors having eigenvalues >1.0 were extracted. The first (“body-fatness”), accounting for 60% of the total variance, loaded heavily on all skinfolds as well as weight and thus represented variation in overall body-fatness, a reflection of current ecological conditions. The second factor (“body-size”), accounting for 16% of the total variance, loaded principally on height and represented variation in overall body-size, that is chronic conditions during development. As predicted, P-level and body-size were significantly positively correlated (r = 0.40, P = 0.005; Fig. 4) (Vitzthum et al., 2002).

7. Conclusion As predicted by the Flexible Response Model, analyses of the Bolivian data from Project Reproduction and Ecology in Provinc´ıa Aroma demonstrate that (1) the probability of ovulation corresponds to acute energy stress, (2) menses duration correlates with fatness level, and (3) progesterone levels correlate with overall body-size (a reflection of chronic environmental conditions during childhood). Compared globally, these Bolivian women have shorter menses duration and lower progesterone levels than women in more developed countries. These findings, in agreement with other studies (Bassol et al., 1984; Fotherby et al., 1980), suggest that hormonal contraceptive dosages designed for women in industrialized countries may be excessively high for those in developing countries. Women with naturally lower progesterone levels, as is seen in these Bolivian women, may experience intolerable levels of side-effects that lead to discontinuation and, potentially, unplanned pregnancy, abortion, and an increased lifetime risk of maternal mortality. We have often heard Bolivian women and health workers express concern about negative experiences with hormonal contraceptives. Contrary to arguments that non-compliance is more a matter of education and economics than biology, these data succinctly support the reports of these women that negative side-effects of hormonal contraceptives are a real problem. The findings from Project REPA are also relevant to understanding the etiology of breast cancer. Substantial data suggests that increased levels of ovarian steroids are a risk factor for cancers of the breast and reproductive tract. In addition to the changes in reproductive patterns that increase menstrual cycle frequency, conditions experienced during childhood may be an important factor responsible for elevating reproductive steroids. The greater dietary quality and quantity available in more developed countries may not only be responsible for greater height and weight in children in more developed countries compared to those in less developed countries, but may also underlie relatively higher steroid levels. The secular trend of increasing height in more developed countries over the last century is well documented and principally attributed to improved diet and reductions in infectious disease (Bogin, 1999; Komlos and Cuff, 1998). These Bolivian data suggest that an increase in height (and overall body-size) is associated with an increase in adult reproductive steroids. This relationship can explain, in part, the observation that second generation migrants to the US from populations characterized by relatively low reproductive steroids and shorter stature are found to have both relatively increased stature and elevated reproductive steroids.

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Also consistent with our findings, epidemiological studies have observed a strong positive association between body-size, particularly height, and risk of breast cancer (Friedenreich, 2001; Ziegler et al., 1996). Also pertinent is the observation that ovarian steroid levels are substantially higher in US women than in other populations, that the US women fall towards the high end of the range of observed menses durations, and that the US has among the highest breast cancer rates. Bolivian women have low ovarian steroid levels and short menses duration, and women in the high Andes have among the lowest age-adjusted risk of breast cancer worldwide (PAHO, 1999). These associations suggest that targeting women with larger body-size, longer menses, and higher reproductive steroids for monitoring could become part of effective breast cancer early detection screening programs. It also suggests that population-level average increases in these variables may portend later increases in breast cancer rates. 7.1. Biological mechanisms linking economics and women’s health The incorporation of an evolutionary perspective adds a new dimension to current thinking on how economic conditions can influence human biology. There is abundant evidence of the numerous behavioral, technological, cultural, and social mechanisms that link economic conditions to human health. But it has generally been assumed that the basic biological functioning of humans does not vary much in the absence of pathology. As a result, the human organism is metaphorically perceived as a machine requiring only the proper care to function well or a tabula rasa upon which the environment (physical, social, cultural and economic) leaves its mark. Instead, evolutionary theory, and the Flexible Response Model specifically, argues that organisms are adapted (in the genetic sense) to their environmental conditions, the result of natural selection acting over many generations, and continue to adapt (i.e. acclimatize or adjust) to those conditions throughout their lifetime. This is not to suggest that either the genetic or non-genetic adaptations are perfect in any sense. Nor does an adaptive mechanism necessarily lead to a healthy organism. It is the recognition of this principal that can lead us to understand how the potential benefits of excellent dietary intake in youth, leading to increased body-size, can also be the cause of breast cancer in later life. Thus, to begin to discern the varied ways in which economic conditions can impact human health necessitates attending to the varying life histories of individuals and evolutionary histories of populations. In addition to being of theoretical interest, understanding the causes of variation in reproductive health is critical to the implementation of sound policies, particularly in the face of a still expanding global population, limited resources and “donor fatigue”. In more developed countries, contraceptive dosages have been carefully developed to meet the needs of clients, modern obstetric practices are widespread, and medical facilities provide detection and treatment of breast cancer. In less developed countries, available hormonal contraceptives may have excessively high dosages, and modern medical facilities for obstetrics and breast cancer care are limited. Increases in the standard of living will not necessarily alleviate these disparities. Rapid urbanization and industrialization in less developed countries, generally viewed as signs of economic improvement, have not been generally accompanied by an equally paced

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development of modern health measures, creating a rise in chronic/non-infectious diseases in the face of still high infectious disease rates. Current socio-economic trends appear likely to exacerbate this double burden of disease, in turn further negatively affecting economic development, environmental quality, and human well-being. In many settings, women bear the largest part of this burden, being subject both to the morbidity and mortality associated with their reproductive roles as well as those afflictions common to all but without the social standing and/or economic independence necessary to attend to their own health. The totality of evidence supports the importance of socio-economic development in improving women’s reproductive health. The evidence also implies that this development is not enough.

Acknowledgements While no agency, organization or other persons are responsible for our views, we nonetheless appreciate the helpful commentary of the reviewers and editor, and thank the organizers (John Komlos and Jorg Baten) and participants of the First International Conference on Economics and Human Biology (University of Tuebingen, Germany, 10–13 July 2002). The Instituto Boliviano de Biolog´ıa de Altura (La Paz, Bolivia) generously furnished logistical support for our investigations (funded by the US National Science Foundation and the University of California). Above all, our unwavering gratitude goes to the women who participated in these studies; their efforts will hopefully take us one step closer to reproductive health for all.

References AbouZahr, C., Wardlaw, T., 2001. Maternal mortality at the end of a decade: signs of progress? Bull. World Health Org. 79, 561–568. Barros, F., Victora, C., Vaughan, J., Tomasi, E., Horta, B., Cesar, J., Menezes, A., Halpern, R., Post, C., Garcia, M., 2001. The epidemiological transition in maternal and child health in a Brazilian City, 1982–1993: a comparison of two population-based cohorts. Paediatric Perinatal Epidemiol. 15, 4–11. Bassol, S., Garza-Flores, J., Cravioto, M.C., et al., 1984. Ovarian function following a single administration of DMPA at different doses. Fertil. Steril. 42, 216–222. Bogin, B.A., 1999. Patterns of Human Growth, second ed. Cambridge University Press, Cambridge. Burnet, F., 1962. Natural History of Infectious Disease. Cambridge University Press, Cambridge. Caldwell, J., Findley, S., Caldwell, P., Santow, G., Cosford, W., Braid, J., Broers-Freeman, D., 1990. What We Know About the Health Transition: The Cultural, Social and Behavioral Determinants of Health. Australian National University, Canberra. Eaton, S.B., M.C., P., R.V., S., Lee N.C., Trussell, J., Hatcher, R.A., Wood, J.W., Worthman, C.M., Jones, N.G., Konner, M.J, et al., 1994. Women’s reproductive cancers in evolutionary context. Quart. Rev. Biol. 69, 353–367. Ehrlich, P., 1968. The Population Bomb. Buccaneer Books, Cutchogue, New York. Ewald, P., 1994. Evolution of Infectious Disease. Oxford University Press, New York. Fathalla, M.F., 1992. Reproductive health: a global overview. Early Hum. Dev. 29, 35–42. Fotherby, K., Koetsawang, S., Mathrubutham, M., 1980. Pharmacokinetic study of different doses of Depo Provera. Contraception 22, 527–538. Freedman, L.P., Maine, D., 1993. Women’s mortality: a legacy of neglect. In: Gay, J. (Ed.), The Health of Women: A Global Perspective. Westview, Boulder, pp. 147–170. Friedenreich, C.M., 2001. Review of anthropometric factors and breast cancer risk. Eur. J. Cancer Prev. 10, 15–32.

V.J. Vitzthum, H. Spielvogel / Economics and Human Biology 1 (2003) 223–242

241

Frisch, R.E., 2002. Female Fertility and the Body-Fat Connection. University of Chicago Press, Chicago. Frisch, R.E., McArthur, J.W., 1974. Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science 185, 949–951. Jamison, D.T., Mosley, W.H., Measham, A.R., Bobadilla, J.L., 1993. Disease Control Priorities in Developing Countries. Oxford University Press, Oxford. Kane, P., 2000. Reproductive health needs worldwide: constraints to fertility control. Reprod. Fertil. Dev. 12, 435–442. Kaunitz, A., Spence, C., Danielson, T., Rochat, R., Grimes, A., 1984. Perinatal and maternal mortality in a religious group avoiding obstetric care. Am. J. Obst. Gynecol. 150, 826–832. Koblinsky, M., Campbell, O.M.R., Harlow, S.D., 1993. Mother and more: a broader perspective on women’s health. In: Gay, J. (Ed.), The Health of Women: A Global Perspective. Westview, Boulder, pp. 33–62. Komlos, J., Baten, J., 1998. In: Proceedings of the Conference on the Biological Standard of Living in Comparative Perspective. Munich, 18–13 January 1997, Franz Steiner Verlag, Stuttgart. Komlos, J., Cuff, T., 1998. Classics of Anthropometric History: A Selected Anthology. Scripta Mercaturae, St. Katharinen, Germany. Livingstone, F.B., 1958. Anthropological implications of sickle cell distribution in West Africa. Am. Anthropol. 60, 533–562. Lohman, T.G., Roche, A.F., Martorell, R., 1988. Anthropometric Standardization Reference Manual. Human Kinetics Books, Champaign, IL. Loudon, I., 2000. Maternal mortality in the past and its relevance to developing countries today. Am. J. Clin. Nutr. 72 (Suppl.), 241S–246S. Lu, Y.-C., Bentley, G.R., Gann, P.H., et al., 1999. Salivary estradiol and progesterone levels in conception and non-conception cycles in women. Evaluation of a new assay for salivary estradiol. Fertil. Steril. 71, 863–868. Mackenbach, J., 1994. The epidemiologic transition theory. J. Epidemiol. Community Health 48, 329–332. Maine, D., Rosenfield, A., 1999. The Safe Motherhood Initiative: why has it stalled? Am. J. Public Health 89, 480–482. Miller, A., Spielvogel, H., Vitzthum, V.J., 2002. Does menses duration in rural Aymara women covary with nutritional status? In: Paper Presented at the Human Biology Association. Buffalo, NY. Olshansky, S., Ault, A., 1986. The fourth stage of the epidemiologic transition: the age of delayed degenerative diseases. Milbank Memorial Fund Quart. 64, 355–391. Olshansky, S., Carnes, B., Rogers, R., Smith, L., 1997. Infectious diseases—new and ancient threats to world health. Popul. Bull. 52. Omran, A.R., 1971. The epidemiologic transition: a theory of the epidemiology of population change. Milbank Memorial Fund Quart. 49, 509–538. Omran, A.R., 1983. The epidemiologic transition theory: a preliminary update. J. Trop. Pediatrics 29, 305–316. Osmani, S., Sen, A., 2003. The hidden penalties of gender inequality: fetal origins of ill-health. Econ. Hum. Biol. 1, 105–122. Pan American Health Organization, 1999. Health Statistics from the Americas. Mortality Since 1960. Pan American Health Organization, Washington, DC, 1991. Rosenberg, M., Rosenthal, S., 1987. Reproductive mortality in the United States: recent trends and methodological considerations. Am. J. Public Health 77, 833–886. Small-Raynor, M., Phillips, D., 1999. Late stages of epidemiological transition: health status in the developed world. Health Place 5, 209–222. Trevathan, W.R., Smith, E., Mckenna, J.J., 1999. Evolutionary Medicine. Oxford University Press, New York. United Nations, 1994. Programme of Action of the United Nations International Conference on Population and Development, Cairo. URL: http://www.iisd.ca/linkages/Cairo/program/p00000.html. Vitzthum, V.J., 1990. An Adaptational Model of Ovarian Function. Population Studies Center, University of Michigan, Ann Arbor. Vitzthum, V.J., 1997. Flexibility and paradox: the nature of adaptation in human reproduction. In: Morbeck, M.E., Zihlman, A. (Eds.), The Evolving Female: A Life History Perspective. Princeton University Press, Princeton, pp. 242–258. Vitzthum, V.J., 2001a. Why not so great is still good enough: Flexible responsiveness in human reproductive functioning. In: Ellison, P.T. (Ed.), Reproductive Ecology and Human Evolution. Aldine de Gruyter, New York, pp. 179–202.

242

V.J. Vitzthum, H. Spielvogel / Economics and Human Biology 1 (2003) 223–242

Vitzthum, V.J., 2001b. The home team advantage: reproduction in women indigenous to high altitude. J. Exp. Biol. 204, 3141–3150. Vitzthum, V.J., Ringheim, K., 2000. Using evolutionary biology to build a better hormonal contraceptive. In: Paper Presented at the Society for Applied Anthropology. San Francisco, CA. Vitzthum, V.J., Spielvogel, H., Caceres, E., Miller, A., 2001. Vaginal bleeding patterns among rural highland Bolivian women: relationship to fecundity and fetal loss. Contraception 64, 319–325. Vitzthum, V.J., Bentley, G.R., Spielvogel, H., Caceres, E., Thornburg, J., Jones, L., Shore, S., Hodges, K.R., Chatterton, R.T., 2002. Salivary progesterone levels and rate of ovulation are significantly lower in poorer than in better-off urban-dwelling Bolivian women. Hum. Reprod. 17, 1906–1913. Waters, W.F., 2001. Globalization, socioeconomic restructuring, and community health. J. Community Health 26, 79–92. World Health Organization (WHO), 1998. Health for All in the 21st Century. URL: http://www.who.int/ archives/hfa/. Ziegler, R.G., Hoover, R.N., Nomura, A.M., et al., 1996. Relative weight, weight change, height, and breast cancer risk in Asian–American women. J. Natl. Cancer Inst. 88, 650–660.