The half-century-long, multigenerational study of over 280,000 nurses has helped shape our understanding of how lifestyle factors affect health and disease—and it’s still going strong today.
Every week, new research studies add information to our understanding of how our lifestyle choices—what we eat, what medications we take, and more—influence our health.
Last month, headlines about the detrimental health effects of butter abounded. And the month before that, reporters covered how long-term yogurt consumption may offer some protection against colorectal cancer.
But how do scientists arrive at these findings? Behind those recent headlines, and many others over the years, is the iconic Nurses’ Health Study (NHS)—one of the most ambitious and fruitful investigations of the risk factors that can lead to chronic diseases.
Running for just short of 50 years, the federally funded NHS study has followed three generations of nurses, using repeated assessments and questionnaires to capture how factors such as lifestyle, social relationships, mental health and biology drive overall women’s health.
Data collected by the NHS has led to the publication of over 4,000 peer-reviewed research papers, with new papers still publishing today.
Mass General Brigham researchers, in collaboration with their colleagues at the Harvard T.H. Chan School of Public Health, have played an integral role in the Nurses' Health Study since its inception and continue to do so today.
Heather Eliassen, ScD, is a co-principal investigator of the first and second generations of the NHS. She is professor of nutrition and epidemiology at the Harvard T. H. Chan School of Public Health and the associate director of the Channing Division of Network Medicine at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system.
Her research examines factors that may contribute to risk of breast cancer, including preventive factors, such as medications and lifestyle choices.
“Broadly, the NHS has shown us that there is a lot we can do to reduce our risk of developing chronic diseases,” Eliassen says.
“This information has driven national and international policy, health insurance plans, and clinical recommendations that have played a massive role in improving public health over the last five decades.”
A Brief History of the Nurses Health Study
So how did the NHS start?
In the late 1960s and early 1970s, oral contraceptive pills were gaining popularity, and Frank Speizer, MD, a physician at BWH and professor at the Harvard T. H. Chan School, wanted to understand the long-term health impacts of taking contraceptives.
For inspiration, he looked to the British Doctor study, which mailed questionnaires to doctors to understand the long-term health effects of smoking.
He first decided to send questionnaires about contraceptive use and health to doctors’ wives. But there was a problem.
“Following up [on their initial responses] with another questionnaire, many of the women in the study said, ‘I’ve never seen this questionnaire before,’” said Eliassen. “It turns out the doctors were filling it out on their wives’ behalf.”
It quickly became clear that this study design would not work, so Speizer and colleagues devised another idea—giving the questionnaire to nurses.
With this revised plan and the support of crucial funding from the National Institutes of Health, the Nurses’ Health Study was born. It was to be jointly conducted by three institutions: BWH, Harvard Medical School, and the Harvard T.H. Chan School.
Nurses turned out to be the ideal study population, according to the researchers, and selecting them as participants a primary reason it has been so successful.
The nursing profession was predominately women at the time, and the study participants had in-depth knowledge of diseases and medications, including brands and doses, which allowed them to accurately self-report detailed health information.
The nurses also turned out to be highly motivated and dedicated participants, with follow-up rates on the questionnaires exceeding 90%—a rate unparalleled in studies today.
The study's initial focus helped to answer key questions about oral contraceptives and breast cancer risk, But researchers realized that the NHS had the potential to answer other key questions about health.
“When we follow 100,000 women for multiple decades, it allows us to investigate different diseases that develop in a population over time,” Eliassen explains. “We have been able to study not just risk of cancer, but cardiovascular disease, neurodegenerative disease and psychosocial wellness.”
Forty-Nine Years and Three Generations
The study began in 1976 with a cohort of 121,700 women, and about half of those participants continued contributing information into their late seventies and beyond.
It grew to include a second cohort in 1989, with a focus on early life exposures and potential preventive factors related to cancer development, with participants whose ages now range from 61 to 78.
The third and most recent generation began enrollment in 2010 and is an open cohort, meaning it constantly recruits participants ages 18 to 61 while collecting data.
The studies now total more than 280,000 current participants of vast ages and backgrounds, making it one of the largest investigations into risk factors for major chronic diseases in women.
Over the years, the NHS team has been able to collect more types of biological specimens that can be used to answer a larger breadth of questions.
“Having nurses all around the country allowed us to send them kits with blood collection supplies,” says Eliassen. “In the original cohort, we had almost 33,000 women who collected their own blood samples or had a colleague collect them before shipping them back to us overnight.”
In addition to blood samples, the NHS has collected urine and stool samples in a biobank, which opens doors to a much more in-depth understanding of disease at the biological level—by looking at markers such as hormones, inflammatory proteins, or microbiome species that are related to health and disease.
Researchers can use modern techniques to look at hundreds or thousands of biomarkers at once in order to understand how the entire profile of biological components, like individual instruments in a larger orchestra, contributes to disease.
NHS has also served as a launchpad for other large cohort studies, including the Growing Up Today Study (GUTS), founded in 1996, which follows over 27,000 children of the second generation of NHS' participants who are now adults.
This multigenerational study provides a way to answer many more questions about how a parent’s health and environment influence their children’s health.
NHS Today
As the NHS approaches its 50th year, it continues to push through barriers to improve public health.
“We receive around 100 requests from researchers to use NHS data for collaborative projects every year,” said Jorge Chavarro, MD, ScD, professor of nutrition at the Harvard Chan School, a physician investigator in the Department of Medicine at BWH, and the principal investigator of NHS3.
Through many of those collaborations, the NHS has changed the way we think about how diet contributes to health and disease.
It has been instrumental in informing U.S. Dietary Guidelines and labeling on nutrition facts—including the landmark findings of linking trans fats to heart disease and sugar-sweetened beverages to type II diabetes.
The subsequent ban on trans fats in the U.S. has prevented over 1 million estimated premature deaths.
The NHS continues to guide our understanding of nutrition by identifying foods associated with disease risk or prevention, like a recent Neurology paper linking red meat consumption to dementia and cognitive decline.
The work also extends beyond human diet to environmental health. A recent study published in the American Journal of Clinical Nutrition, which highlighted a dietary pattern associated with both reduced risk of premature death and lower environmental impact, outlined potential ways to adjust the food supply so that it is both more nutritious and more protective of the essential natural resources we rely on.
In addition to diet, the NHS has recently made strides in our understanding of mental health. A recent study in JAMA Network Open found that strong attachment to pets, particularly dogs, is linked to lower anxiety and depression symptoms, especially in women who have a history of childhood abuse.
This work is one example of how a lifestyle intervention—getting a pet—might be beneficial for improving mental health outcomes.
While all these new results have been coming out, the study has also been evolving its methods of data collection.
Chavarro leads the third generation of the study (NHS3), which in contrast to the previous two generations that sent the questionnaires by mail, collects data entirely online.
“That changes how you interact with participants, and how participants experience the study,” says Chavarro. “They are getting emails from us all the time, rather than a questionnaire every so often. This allows us to be more flexible on things that are very important for a small number of people.”
With this increased flexibility, Chavarro has been able to identify specific subgroups of women, like those who are planning to become pregnant, and ask them questions about what is happening during their pregnancy in real time.
“One big emphasis of NHS3 so far has been on reproductive health, and identifying health outcomes and complications related to the preconception period, pregnancy and beyond,” he says.
NHS3 investigators have described how pregnancy intention changes over time and how this influences pregnancy itself. They have also identified how novel factors, such as consumption of energy drinks, impacts the risk of developing pregnancy complications.
My hope is that the study will keep going for a long time and will impact areas of women’s health that haven’t been addressed before. If you have daughters and granddaughters as I do, and you want to hand down a legacy to future generations and this is the way to do it.
NHS Participant and Brigham Legacy Society member
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I was honored to take part in something so much bigger than myself, it’s a good feeling.
NHS2 Participant and Brigham Legacy Society member
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What’s Next for NHS
Since the beginning, NHS has been supported by federal funding, largely from the National Institutes of Health (NIH), specifically the National Cancer Institute (NCI), and more recently the National Heart, Lung and Blood Institute (NHLBI).
But the NCI recently phased out a funding mechanism for epidemiology cohort studies such as the NHS, and federal research grants face growing uncertainty amid shifting administration priorities.
“We are working really hard to keep the science going and broadening our funding portfolio through grants and philanthropy,” says Chavarro. “Fortunately, we are in an environment where we have many extremely talented people who write compelling grants that help us maintain these incredible and precious resources in a very competitive landscape.
"With sustained support, we can build on this legacy of discovery, continue to learn more about the drivers of human health and disease, and find ways to help everyone live healthier lives.”
Research at Mass General Brigham
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