Nurses’ Health Study (original cohort)

The Nurses’ Health Study was established by Dr. Frank Speizer in 1976 with funding from the National Institutes of Health. The primary motivation in starting the NHS was to investigate the potential long term consequences of the use of oral contraceptives, a potent drug that was being prescribed to hundreds of millions of normal women.

Registered nurses were selected to be followed prospectively. We anticipated because of their nursing education, they would be able to respond with a high degree of accuracy to brief, technically-worded questionnaires and would be motivated to participate in a long term study.

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

Approximately 122,000 nurses out of the 170,000 mailed responded. 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 we recognized that diet and nutrition would play important roles in the development chronic diseases, in 1980, the first food frequency questionnaire was collected. Subsequent diet questionnaires were collected in 1984, 1986 and every four years since.

At the request of some of the nurses and with the addition of investigators to the research team interested in quality of life issues, question related to quality-of-life were added in 1992 and repeated every four years.

Because certain aspects of diet cannot be measured by questionnaire, particularly minerals that become incorporated in food from the soil in which it is grown, the nurses submitted 68,000 sets of toenail samples between the 1982 and 1984 questionnaires.

Similarly, to identify potential biomarkers, such as hormone levels and genetic markers, 33,000 blood samples were collected in 1989-90 followed by second samples from 18,700 of these participants in 2000-01. These samples are stored and used in case/control analyses.

As of this writing, response rates to our questionnaires are at 90% for each two-year cycle.

Nurses’ Health Study II

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

This younger generation 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 risk of breast cancer provided a particularly strong justification for investment in this large cohort. Further, we planned to collect detailed information on type of oral contraceptive used, which was not obtained in the Nurses’ Health Study.

The initial target population was women between the ages of 25 and 42 years in 1989; the upper age was to correspond with the lowest age group in the Nurses’ Health Study. The original goal was to enroll 125,000 women. Our strategy was to do a single mailing inviting women to enroll and then only enroll the most enthusiastic potential participants who would complete a single questionnaire after one request, thus identifying those who would be most likely to continue participation during the follow-up period.

We anticipated that follow-up in this population might be complicated and difficult because it represented the time of life where names might change because of marriage, professional changes would be frequent, and women would have complicated, busy lives because of child-bearing.

We contacted state nursing boards in states with large populations and in states whose nursing boards were able to provide information on gender and date of birth or age. The following states were included in the initial mailing: California, Connecticut, Indiana, Iowa, Kentucky, Massachusetts, Michigan, Missouri, New York, North Carolina, Ohio, Pennsylvania, South Carolina and Texas. The overall response rate to the baseline mailing was approximately 24% (123,000 of 517,000.) After exclusions for incomplete forms and women who did not meet study criteria, a total of 116,686 women remained in Nurses’ Health Study II.

Developing the baseline questionnaire, we relied heavily on our experience from the Nurses’ Health Study. We conducted a number of small pilot studies to optimize the wording for the complex questions on lifetime oral contraceptive use, particularly to make them suitable for an optically scannable format. We also sent draft versions of the questionnaire to leading colleagues in the field of breast cancer research and incorporated their feedback into the final version. A color booklet containing pictures of all oral contraceptive preparations ever sold in the United States was developed and mailed to participants with the baseline questionnaire.

Every two years, cohort members receive a follow-up questionnaire with questions about diseases and health-related topics including smoking, hormone use, pregnancy history, menopausal status. In 1991, the first food-frequency questionnaire was collected and subsequent food-frequency questionnaires are administered at four-year intervals. A two-page quality-of-life supplement was included in the first mailing of the 1993 and 1997 questionnaires.

Blood and urine samples from approximately 30,000 nurses were collected in the late 1990′s.

As of this writing, response rates to NHS II questionnaires are at 90% for each two-year cycle.

Nurses’ Health Study III

In 2010, Drs. Walter Willett, Janet Rich-Edwards, Stacey Missmer, and Jorge Chavarro started Nurses’ Health Study 3 in collaboration with investigators at the Channing Laboratory and the Harvard School of Public Health. For the first time ever, the study is entirely web-based. Participants include female LPN/LVNs and RNs, and it’s also open to nurses in Canada. NHS3 aims to be more representative of nurses’ diverse backgrounds.  It will closely look at health issues related to lifestyle, fertility/pregnancy, environment, and nursing exposures.  Join now at www.nhs3.org


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