Fertility for many women is a mixed blessing, points out Associate Professor Marlene Goldman, SD’84. For many of their reproductive years, women want to avoid pregnancy. But women who want to have children need to keep their fertility intact. "A woman’s reproductive life lasts about 40 years, but most women have their children in the space of only four years," notes Goldman, a member of the School’s epidemiology department faculty.

With this paradox in mind, Goldman recognized several years ago there was a dearth of research on the risk factors for infertility at a time when it seemed to be a growing problem. More women were seeking medical care for the condition as treatments were aggressively marketed. In addition, some studies showed that the prevalence of infertility was climbing as women postponed attempting to have children until their late 30s or early 40s. So starting in the early 1990s and working in collaboration with several other researchers at the School and Harvard Medical School, Goldman began a pathbreaking series of U.S.-based epidemiologic studies aimed at sorting out some of the risk factors for infertility.

The picture that has emerged from the findings of Goldman and others is a rather complicated one. She and her collaborators have found some telling associations between weight and infertility. Alcohol and caffeine consumption patterns also have been found to play a role. Recent research on fibroids and infertility is suggestive, but it is unclear whether fibroids actively prevent pregnancy or are the result of another factor that is also related to infertility. Janet Daling, the distinguished University of Washington epidemiologist who has published extensively on infertility, credits Goldman’s work with making "a real contribution to the causes of infertility and the types of infertility that exist."

In her work Goldman has depended on data collected by Daniel Cramer, a Harvard Medical School associate professor of obstetrics and gynecology, and by the School-based Nurses’ Health Study II, a cohort of 11,600 younger nurses that has been studied since 1989 (the first Nurses’ Health Study started in 1976). Given the many studies connecting exercise and diet to health, it might seem obvious to ask questions about how these kinds of lifestyle factors might affect a woman’s reproductive health. But Goldman says it was obvious only in hindsight: "At the time we started them, studies like this hadn’t been done before. Very little was known about what caused infertility."

In one key study published in Epidemiology in March 1994, Goldman and her collaborators looked at how body weight influenced conception. Going into the project, Goldman and her colleagues knew that athletic women with atypically low body fat often have irregular menstrual cycles, but no one had asked directly how weight might influence infertility. Using data from the largest case-control study on infertility, Goldman and her colleagues showed that infertility was, indeed, associated with both below- and above-normal weight. Consistent with previous research about athletes and irregular menstrual cycles, the paper reported that women who were underweight had a 60 percent greater chance of infertility compared to women in the normal weight range. But the greater risk turned out to be on the overweight end of the spectrum: obese women were three times more likely to be infertile than women in the normal weight range, and even moderately overweight women had an increased risk of infertility. Similar results were found in a second study using Nurses’ Health Study II data. "We were certainly surprised that the risks rose as quickly as they did at moderate levels of overweight," says Janet Rich-Edwards, the study’s lead author. Goldman and her collaborators had more surprises when they looked at alcohol and caffeine consumption; both moderate and heavy amounts of either added some infertility risk, albeit fairly slight.

Fibroids are benign tumors of the smooth muscle lining in the uterus that clinicians long suspected contributed to infertility. Lynn Marshall, a former graduate student at the School now working in Oregon, says Goldman-led research showed that infertile women do, in fact, have a higher chance of developing fibroids than other women. Early menses and taking oral contraceptives at a young age were also linked to fibroids. Marshall says the oral contraceptive finding was a first: "It’s important because the number of women beginning to use contraceptives at a young age is increasing." Yet according to Goldman, whether fibroids cause infertility remains an open question. While observational epidemiologic research has definitely found an association between fibroids and infertility, it hasn’t proven a definite cause-and-effect relationship (which is, of course, a limitation of all observational research).

For almost 20 years now, Goldman has been part of the health research world focused on identifying risk factors for all kinds of diseases and health conditions, not just infertility. The findings have proliferated. The meaning for health has been profound. Yet Goldman has some misgivings: "I sometimes feel that all that’s being accomplished is to confuse the public." To bring some order to the health information onslaught, Goldman decided several years ago to write and edit a comprehensive textbook about women’s health; Women and Health is scheduled to be published this fall by Academic Press. Goldman did a lot of work on the book as a 1998—99 Bunting Institute Fellow. "Her book is 100 chapters on the state of the art in women’s health research," says Rita Nakashima Brock, director of the prestigious fellowship program based at Radcliffe. By producing this book, says Brock, Goldman is "doing something that no one else is doing in the world."

-- Judy Silber