The Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) are among the largest prospective investigations into the risk factors for major chronic diseases in women.

Former Secretary of the U.S. Department of Health and Human Services Donna Shalala called NHS "one of the most significant studies ever conducted on the health of women."

In addition to reading about the history of the studies below, watch a series of short videos about the studies on the Nurses’ Health Study 3 YouTube page.

Nurses' Health Study: Original cohort

The Nurses' Health Study (NHS) was established by Dr. Frank Speizer in 1976 with continuous funding from the National Institutes of Health since that time. The primary motivation for the study was to investigate the potential long-term consequences of oral contraceptives, which were being prescribed to hundreds of millions of women.

Why nurses?

Nurses were selected as the study population because of their knowledge about health and their ability to provide complete and accurate information regarding various diseases, due to their nursing education.

NHS founders anticipated and found that nurses were able to respond with a high degree of accuracy to brief, technically worded questionnaires. They were relatively easy to follow over time and were motivated to participate in a long-term study. The cohort was limited to married women due to the sensitivity of questions about contraceptive use at that time.

Establishing the cohort

Married registered nurses, aged 30 to 55 in 1976, who lived in the 11 most populous states, and whose nursing boards agreed to supply NHS with their members' names and addresses, were eligible to be enrolled in the cohort if they responded to the NHS baseline questionnaire. The original states were California, Connecticut, Florida, Maryland, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, and Texas.

The names and addresses of 238,026 nurses who fulfilled the eligibility criteria were obtained in 1972 from the American Nurses' Association, with approval from the state boards of nursing. Unique identification numbers were immediately assigned to each nurse to ensure strict confidentiality. The NHS cohort was then established by a series of three mailings of the baseline questionnaire. The first mailing to all 238,026 nurses occurred in June 1976, with the final mailing to non-respondents in December 1976. Overall, 121,700 women returned a completed questionnaire. After excluding 65,613 questionnaires that could not be delivered, the response rate was approximately 71% (121,700 of 172,413).

Research focus over time

The original focus of the study was on contraceptive methods, smoking, cancer, and heart disease, but has expanded over time to include research on many other lifestyle factors, behaviors, personal characteristics, and more than 30 diseases.

Every two years, cohort members receive a follow-up questionnaire with questions about diseases and health-related topics, including smoking, hormone use, and menopausal status.

Because the investigators recognized that diet and nutrition likely played an important role in the development of chronic diseases, a food-frequency questionnaire for collecting dietary information was added in 1980 and continues to be mailed at four-year intervals. Also, a quality-of-life supplement was first included with the questionnaire in 1992 and is re-administered at regular intervals.

Numerous supplemental questionnaires have been sent to selected participants to provide additional data for specific research questions and to better describe and define reported diseases.

A response rate of at least 90% has been achieved in most follow-up cycles of questionnaires.

From questionnaires to biological samples

Because certain aspects of diet cannot be measured by questionnaires, for example, minerals from the soil where food was grown, 63,000 nurses submitted toenail samples between the 1982 and 1984 questionnaires.

Blood samples were collected from nearly 33,000 participants in 1989-90 to identify potential biomarkers such as hormone levels and genetic markers, followed by a second blood and urine sample from more than 18,700 of the same participants in 2000-02. These samples are stored and used to study the relationship between various biologic markers and disease risk. DNA was collected from cheek cells from an additional 33,000 women in 2001-2004.

Nurses' Health Study II

The Nurses' Health Study II (NHS II) was established by Dr. Walter Willett and colleagues in 1989 with funding from the National Institutes of Health to study oral contraceptives, diet, and lifestyle risk factors in a population younger than the original NHS cohort.

Why a new cohort of nurses?

This younger generation of nurses included women who started using oral contraceptives during adolescence and were thus maximally exposed during their early reproductive life. Several case-control studies suggesting such exposures might be associated with substantial increases in breast cancer risk provided a particularly strong justification for investment in this large cohort. Researchers also planned to collect detailed information on the types of oral contraceptives used, which was not obtained in the Nurses' Health Study.

In addition, NHS II obtained information on physical activity and diet in adolescence and early adult life.  

Establishing the cohort

The target population for NHS II was women between 25 and 42 years old in 1989; the upper age corresponded with the lowest age group in the Nurses' Health Study at that time. The NHS II enrollment strategy consisted of a single mailing. Only the potential participants who completed a questionnaire after one request were enrolled, thus identifying the most enthusiastic nurses who would be most likely to continue participating throughout the study.

Investigators contacted state nursing boards that were able to provide information on gender and date of birth or age, and that were in states with large populations. The states in the mailing included: California, Connecticut, Indiana, Iowa, Kentucky, Massachusetts, Michigan, Missouri, New York, North Carolina, Ohio, Pennsylvania, South Carolina, and Texas.

The original goal was to enroll 125,000 women. From the 517,000 baseline questionnaires mailed, the overall response rate was approximately 24% (123,000 of 517,000). After exclusions for incomplete forms and ineligibility, a total of 116,430 women remained in NHS II cohort.

Research focus

Every two years, cohort members receive a follow-up questionnaire with questions about diseases and health-related topics, including smoking, hormone use, pregnancy history, and menopausal status. Response rates to NHS II questionnaires are 85-90% for each two-year cycle.

In 1991, the first food-frequency questionnaire was collected, and continues to be administered at four-year intervals. Items on quality of life were first included on the 1993 questionnaire and continue to be administered every four years.

From questionnaires to biological samples

Blood and urine samples from approximately 30,000 nurses, many of whom were premenopausal, were collected in 1996-1999. Over 18,500 of these women gave two blood samples and one urine sample timed within the menstrual cycle. This collection is very unique, allowing our researchers to study how premenopausal hormone levels influence disease risk. A second blood and urine sample from approximately 16,500 of the same participants was obtained in 2010-2012, when most of the women were postmenopausal. DNA from cheek cells was collected in 2006 from another 30,000 women.

Nurses' Health Study 3

In 2010, Drs. Jorge Chavarro, Walter Willett, Janet Rich-Edwards, and Stacey Missmer launched the Nurses' Health Study 3 (NHS 3) in collaboration with investigators at the Channing Division of Network Medicine at Brigham and Women's Hospital, Harvard Medical School, and the Harvard T.H. Chan School of Public Health. It is the first of the Nurses' Health Studies to be entirely web-based and includes different types of health workers, as well as both men and women.

NHS3 participants

Participants include LPN/LVNs and RNs ages 19-46. An important goal for NHS 3 is to include nurses from more diverse ethnic backgrounds than in the prior Nurses' Health Studies. NHS3 is also open to nurses in Canada and, for the first time, includes male nurses. Enrollment is still open; for more information, including how to join, visit www.nhs3.org.

Research focus

NHS 3 is examining how dietary patterns, lifestyle, environment, and nursing occupational exposures impact men's and women's health. The study is also looking closely at women's health issues related to new hormone preparations and fertility/pregnancy, and includes a greater focus on adolescent diet and breast cancer risk.

Nurses already enrolled in the Nurses' Health Studies have been invaluable in recruiting new participants. Your passionate commitment and strong support are enormously appreciated. Tell a nurse about NHS3.