30 Years and Counting: The Women's Health Initiative Improves Lives and Grows Researchers
The numbers don’t lie. The Women’s Health Initiative (WHI), of which UB is the Northeast Regional Center, has been producing remarkable work related to post-menopausal women’s health for 30 years.
Some 400 ancillary WHI studies received additional funding over that time. More than 2,350 papers have been published based on WHI studies and findings. This longitudinal study focused on post-menopausal women's health initially enrolled a diverse group of more than 161,000 participants nationwide, including nearly 4,000 women from Western New York, who donated some 5.3 million vials of blood and other biospecimens.
The true significance of the work of WHI, however, isn’t measured in numbers: It’s measured in the ongoing influence on clinical practice, the greater focus on women’s health, and, perhaps as importantly, on the careers of the scientists, researchers and students who have continuously mined WHI data for 30 years to gain new knowledge of what contributes to women’s healthy, long lives.
A landmark study
The U.S. National Institutes of Health (NIH) initiated WHI in 1991 amid growing concerns about the lack of basic research into women’s health and a specific concern about the risks and benefits of using hormone therapy. WHI’s aims from the start were to address postmenopausal women's health issues and offer insights into ways to prevent conditions like heart disease, breast and colorectal cancer, and osteoporosis.
Among the 16 “vanguard clinical centers” across the U.S. commencing the massive undertaking in 1993 was WHI’s University at Buffalo Clinical Center. Housed at UB, the center’s lead investigator was Jean Wactawski-Wende, PhD, now dean of UB’s School of Public Health and Health Professions. With her epidemiological research interests in women's health, Wactawski-Wende has been an active and guiding presence in the WHI’s initial—and continuing—work. She now leads the entire northeast region of WHI.
More than 68,000 post-menopausal women between the ages of 50 and 79 enrolled in WHI’s initial clinical trials:
- Hormone Therapy (HT) Trial, investigating the benefits and risks of combined estrogen and progestin hormone therapy and estrogen alone, compared to placebo, in post-menopausal women.
- Dietary Modification Trial, focused on the effects of a low-fat/high-fiber diet on breast and colorectal cancer and heart disease.
- Calcium and Vitamin D Supplementation Trial, examining the impact of calcium and vitamin D supplementation on the prevention of hip fractures and colorectal cancer.
WHI also ran an observational study tracking the medical histories and health habits of more than 93,000 women, which added (and continues to add) information that complemented the clinical trials.
One of the most significant findings that emerged from the WHI was related to hormone therapy, which sent what can only be described as shock waves through standard clinical practice at the time. The HT trial found that combined estrogen and progestin hormone therapy actually increased the risk of breast cancer, stroke, and blood clots and heart disease, while it decreased the risk of colorectal cancer and hip fractures. The study also showed that the risks outweighed the benefits for many women, leading to a shift in medical recommendations regarding hormone therapy for post-menopausal women. According to a paper based on the HT trial, the U.S. saw 126,000 fewer breast cancer cases as a result of a reduction in the use of HT. Although it revealed fewer risks, the estrogen-alone trial found more strokes in women taking the medication.
As for the dietary modification trial, it did not find a significant reduction in the risk of breast cancer, colorectal cancer, or heart disease with a low-fat diet. The study did provide insights into the complex relationships between diet, lifestyle, and health outcomes.
WHI Researchers
Millen first engaged with WHI when she was a grad student at the University of Wisconsin. Her advisor there was funded to conduct an ancillary WHI study on diet and age-related eye disease, and Millen was involved with the pilot projects, preliminary data collection and at the very beginning of data collection for the study. She has worked intimately in two WHI ancillary studies, the Carotenoids in Age-Related Eye Disease Study (CAREDS), and the Osteoporosis and Periodontal Disease (OsteoPerio) Study.
"[CAREDS and OsteoPerio] have provided me with opportunities to grow as a scientist through mentorship from these studies’ principal investigators, Dr. Julie Mares and Dean Jean Wactawski-Wende. I have had the opportunity to write many papers on my areas of interest, nutrition, and chronic disease of aging (eye disease and periodontal disease). This has led to my growth as a scientist and contributed new information to the literature on the role of diet in both age-related macular degeneration and periodontal disease. These studies also gave me the opportunity to launch my research career, providing me with access to these data to propose, or be included in, NIH-funded research projects. I have also met many other WHI scientist with a research focus on nutrition. Through interactions with them, I have deepened my understanding of the role of nutrition in women’s health and aging. Furthermore, I have also had the opportunity, through annual meetings, scientific interest groups, and committees, to be exposed to other avenues of reach in WHI (health services, genetics, hormones and women’s health) that have expanded my knowledge base.”
Burns started working with WHI when she began her PhD studies in epidemiology at UB. She is using WHI data to complete each aim of her dissertation, "Associations of a TMAO Dietary Pattern to Metabolic and Gut Microbiome Profiles and Vascular Health.” Her study underpinning the dissertation received a highly prestigious F31 grant from the National Heart, Lung, and Blood Institute/NIH. Burns has also been involved in data collection of a WHI ancillary study on the interplay of diet and the gut microbiome related to age-related macular degeneration, the PI of which is her mentor, Amy Millen.
“I appreciate the support and guidance provided by the professors and researchers who are involved with WHI. In addition, I have been able to build connections with researchers that I may not have otherwise connected with through collaboration on WHI projects. In addition to the skills I have gained in analyzing data from a large population-based cohort study, the collaboration and communication skills gained from being a part of a large research group will benefit my future career.”
SPHHP Dean Jean Wactawski-Wende introduced LaMonte to WHI’s collaborative opportunities soon after he joined UB’s faculty. A self-described “break” came when he joined investigators at five sites around the country who planned and implemented the Objective Physical Activity and Cardiovascular Health (OPACH) Study in Older Women, a five-year epidemiologic cohort study funded by the National Heart, Blood, and Lung Institute. He also chairs the WHI Physical Activity Scientific Interest Group and represents the WHI on a national consortium pertaining to heart failure.
"In addition to opportunities nationally, I have had the privilege of working with Jean [Wactawski-Wende] and other UB faculty on the ongoing epidemiologic Osteoporosis and Periodontal Disease (OsteoPerio) Study. We recently completed an in-clinic examination of around 500 women in their 80s and 90s that I took part in, completing some of the measures of physical performance. I cannot begin to express the joy I felt in talking with the ladies, hearing their stories about first enrolling in WHI and then all that has happened over their years of participation and, of course, about their own life experiences. Nothing I do as a scientist or as a university professor affords me such tangible understanding about how our work is perceived and how it affects individual people.”
Ochs-Balcom began to work on the WHI study as a graduate student. Her tenure coincided with the time when the hormone therapy trials were stopped early, so she was able to witness a key historic moment of the study. She became engaged as a research investigator in 2009 when she had the opportunity to use some of the new genetic data being generated from WHI participants. Since then, Ochs-Balcom has been actively working on different studies in the WHI, becoming more involved with WHI investigators across the country. Her research has focused on genetic susceptibility, breast cancer, health disparities, obesity and body composition, and sleep.
“Our current study, funded by the National Cancer Institute, is focused on how hormones and abdominal obesity that develops after menopause are related to each other, and how specific hormones relate to breast cancer risk. We are excited to be studying follicle stimulating hormone, a hormone that surprisingly has not yet been studied in post-menopausal women. The WHI is a wonderful example of a resource that can improve our knowledge of women’s health, with more than 2,300 papers published to date. It is a powerful tool for educating young scientists. I love hearing stories about the dedication of the WHI participants, in particular. I like to say that women are smart—they know our work can improve and protect the health of future generations.”
Ahmed Soliman, PhD candidate in epidemiology When Soliman joined the epidemiology PhD program at UB, he began working with Jean Wactawski-Wende and Michael LaMonte using data from the OsteoPerio study. The OsteoPerio study is an ancillary study to the larger WHI cohort and is located at the WHI clinical center in Buffalo. He is interested in doing research on the relationship between hormone therapy and the oral microbiome, which the data from the OsteoPerio study gave him the opportunity to pursue.
“As I progressed in my PhD study, I decided to use data from the larger WHI cohort for my dissertation with a focus on cardiovascular disease in post-menopausal women. I also presented my research findings in two annual WHI meetings, which gave me the chance to meet other WHI investigators and get exposed to research conducted outside of Buffalo. Although the WHI clinical centers are spread throughout the U.S., getting to work with WHI investigators made me feel part of a closely related network of researchers dedicated to improving women’s health through their work. The WHI provides a wide range of high-quality data that I can use to answer research questions that meet my interests. Moreover, the WHI investigators are world-renowned researchers that provide great mentorship to early career scientists.”
Multiple benefits
Though many of WHI’s findings made—and continue to make—headlines, an arguably as vital aspect of the study takes place behind the scenes, related to the evolution of junior researchers into experienced investigators continuing to add to the body of knowledge about what keeps women healthy.
During WHI’s three-decade existence, numerous young researchers and students at UB and other WHI centers have mined its data in an effort to expand our understanding of post-menopausal women’s health. Some of UB’s most prolific scientists and promising students, several of whom are featured in this article, are continuing to contribute to the body of knowledge encompassed by WHI. With the National Heart, Lung, and Blood Institute/NIH funding WHI through 2027, the landmark study that “had a profound impact on the understanding of post-menopausal women’s health,” says Wactawski-Wende, will remain a wellspring of knowledge creation on healthy aging and an invaluable engine to train and support research careers.
Ongoing work
Happily for women’s health, WHI continues to advance knowledge of what keeps women living long and active lives through both extension and ancillary studies.
WHI’s extension studies collect long-term data from WHI volunteers to complement the original WHI study. The current extension study collects annual health information from WHI volunteers who agree to take part through 2027, with a focus on heart disease, cardiovascular events, aging, cognition and quality of life.
WHI’s ancillary studies are separate research projects that reach out to and enroll WHI volunteers. SPHHP researchers have been key investigators in some of those studies, benefiting from the opportunities to mine the data, work with researchers with wide-ranging expertise and, in the case of early-stage researchers, evolve their careers.
The Long Life Study (LLS) brought in 7,875 people for clinical measurements and sample donations (biospecimens) in 2012-2013, with a follow-up assessment ongoing since 2022. LLS data and specimens are available to any researchers who could make use of its baseline data to conduct studies on various aspects of aging, health, and disease. In fact, according to Wactawski-Wende, sharing data is a hallmark of WHI, which “gave access to the data to researchers from across the country who needed it. Our goal in sharing the data was—and is—to boost the careers of the next generation of our trainees.”
The Objective Physical Activity and Cardiovascular Health Study (OPACH) used wearable devices to measure how physical activity impacts cardiovascular health in older women. Michael LaMonte, PhD, research professor of epidemiology and environmental health, is one of the national investigators on the study, which strove to understand the amount, type, and intensity of physical activity related to healthy cardiovascular aging in older women. A key result was that the U.S. Department of Health and Human Services’ second set of Physical Activity Guidelines for Americans included the study’s data in the scientific evidence report informing the guidelines’ recommendations for older adults.
According to LaMonte, “The main result of interest was our finding of better cardiometabolic risk factors (e.g., blood cholesterol, glucose, inflammation, etc.) and lower mortality risk in women who were active at lower amounts and intensities than had previously been recommended for public health…the current guidelines now include a statement that ‘any movement is better than none and for older adults it appears substantial health benefits might be obtained through movement in light intensity, habitual activities of daily living.’” OPACH2 is underway, continuing to examine the links between activity and heart health in the same women a decade later.
MASS: Muscle and disease in post-menopausal women and Ms. LILAC (Muscle Mass in the Life and Longevity After Cancer [LILAC] Study) are two studies looking at the decline in lean body mass after menopause, seeking to understand which changes in muscle mass are associated with “normal” aging and which are caused by changes related to underlying age-related diseases such as cancer and diabetes. Defining this difference is a key to future interventions for a growing segment of the population. Research Assistant Professor Hailey Banack, PhD, and Wactawski-Wende are the primary investigators of these R01 studies funded by the National Institutes of Health including the National Cancer Institute and the National Institute on Aging.
Role of FSH in Postmenopausal Obesity and Breast Cancer is honing in on the role follicle stimulating hormone (FSH) plays during menopause and how it contributes to development of post-menopausal obesity and breast cancer. It is the largest study of its kind in older women.
“Our hypothesis is that follicle stimulating hormone is driving weight gain, and the weight gain increases the risk of breast cancer,” says Heather Ochs-Balcom, associate professor of epidemiology and environmental health, and a principal investigator on the study with Jennifer W. Bea at the University of Arizona Cancer Center. Wactawski-Wende is a co-investigator. A hormone released by the pituitary gland, FSH plays an important role in female development and reproduction by stimulating growth of the ovarian follicle before ovulation, Ochs-Balcom explains. The project is funded through a five-year R01 grant from the National Cancer Institute/NIH.
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