Modeling women's health with nonhuman primates and other animals.

Interest in the health problems of women as distinct from those of men is not new (Pinn 2003). The Popular Health Movement of the 1830s and -40s (which targeted health advice to women as the caretakers of their families), the creation of women’s hospitals after the Civil War (which provided a venue for female physicians and nurses to train and practice), and the birth control and maternal and child health movements of the early 1900s all represent major efforts to increase awareness of health concerns specific to women (Weisman 1998). Even so, research investigating diseases and conditions unique to women and evaluating sex differences in the manifestation of common diseases was slow until the very latter part of the 20th century. As late as 1980, for example, the Food and Drug Administration routinely discouraged the inclusion of women in drug trials (Kinney et al. 1981). This exclusionary atmosphere extended also to large clinical trials funded by the National Institutes of Health (NIH), including the Physicians Health Study (Hennekens and Eberlein 1985) and the Multiple Risk Factor Intervention Trial (“MR. FIT” 1982), and is documented in numerous publications (e.g., NIH 1999; Wizemann and Pardue 2000). Change, at least with respect to government policy, began in the mid-1980s with publication of a US Public Health Service Task Force report concluding that women’s health care had been compromised by the failure to conduct research specifically on women’s health issues (USPHS 1985). As a result, the NIH issued a policy encouraging the inclusion of women in research and the assessment of sex differences in research outcomes. However, real transformation of research practices did not begin until an investigation instigated by the Congressional Caucus for Women’s Health revealed poor compliance with the new NIH policy (USGAO 1990). In response to this report and the resulting public and Congressional furor, the NIH established the Office of Research on Women’s Health and initiated a further change in policy that culminated in a new law prescribing the inclusion of women and minorities as subjects in clinical research (PL 103-43 1993). Other NIH actions at this time included the establishment of the Women’s Health Initiative (WHI) in 1991. This 15-yr effort encompasses a controlled clinical trial evaluating effects of hormone replacement therapy, a large observational study assessing predictors of disease, and community-based approaches to developing healthful behavior. The WHI is perhaps the most extensive manifestation of a mandate to address common causes of death, disability, and impaired quality of life in postmenopausal women. Recently, the Institute of Medicine released a report (Exploring the Biological Contributions to Human Health: Does Sex Matter?) that provides an historical perspective on women’s health issues, reviews the current state of science in this area, and makes recommendations for future research (Wizemann and Pardue 2001). Notably, the summary statement calls for increased development and utilization of animal models in the study of sex differences in disease. This recommendation emphasizes nonhuman primates, recognizing that these species probably have the greatest potential for advancing such investigations. In light of this document, it is perhaps appropriate that this issue of ILAR Journal is devoted to the use of animal models in the study of women’s health, and, furthermore, that the major focus is on nonhuman primates. It will be seen from the included articles that these animals, especially monkeys of the genus Macaca, have played a pivotal role in extending understanding of both normal reproductive function and pathobiological processes affecting women. Researchers first made systematic use of macaque monkeys to elucidate the reproductive biology of women. Much of this research was organized around study of the menstrual cycle, a phenomenon shared uniquely by women and the Old World anthropoid primates. The first article in the issue (Kaplan and Manuck 2004) provides a brief summary of this work and then describes a phenomenon (functional hypothalamic anovulation syndrome) in which environmental factors (e.g., psychological “stress,” caloric restriction, and exercise) cause women to transition from normal menJay R. Kaplan, Ph.D., is a Professor in the Departments of Pathology (Comparative Medicine) and Anthropology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.