was not found to affect the incidence of breast cancer. Finally, an increased risk of kidney stones was observed among those taking calcium plus vitamin D. Observational study The Observational study (OS) study recruited eligible postmenopausal women (n = 93676) who were either ineligible or unwilling to participate in the CT portion of the study, for the purpose of obtaining additional risk factor information, identifying risk-related biomarkers, and serving as a comparative observational assessment to the CT interventions. Participants underwent an initial baseline screening, including the collection of physical measurements, blood specimens, an inventory of medications and supplements, and completion of questionnaires pertaining to medical history, family history, reproductive history, lifestyle and behavioral factors, and quality of life. In addition, more specific information was collected with regard to the participant's geographic residence history, passive (i.e., "second-hand") smoking exposure in childhood and adulthood, early life exposures, details of physical activity, weight and weight-cycling history, and occupational exposures. In addition to the baseline data collected, OS participants received annual questionnaire mailings to update selected exposures and outcomes, and were expected to make an additional clinic visit, to include an additional blood collection, about three years post-enrollment. It was planned that participants would be followed for an average of 9 years. The major outcomes of interest for the OS were coronary heart disease, stroke, breast cancer, colorectal cancer, osteoporotic fractures, diabetes, and total mortality. Given the size and diversity of the cohort, taken together with the data and specimen collection being undertaken, it was expected that this cohort could yield insights into a variety of hypotheses, as well as generate new hypotheses with respect to disease etiology in women. OS component findings The WHI OS has and continues to yield many findings and new hypotheses, a small sampling of which are highlighted below: A decrease in invasive and ductal breast cancer incidences with decreasing estrogen/progestin combination therapy usage among the OS cohort, which served to corroborate the controlled HT CT trial findings. Other cancer surveillance studies have noted the same trend. Identification of putative molecular markers which may predispose (and/or aid early detection) certain populations of women to diabetes and breast cancer. Recognition that postmenopausal women are less active than they were during their pre-menopausal years, suggesting a possible benefit for interventions at or around perimenopause. Furthermore, this decrease in activity (e.g., prolonged sedentary activity) can lead to an increased CVD risk. A