In 2002, the Writing Group for the Women's Health Initiative Investigators published the article Risks and Benefits of Estrogen Plus Progestin in Healthy, Postmenopausal Women: Principal Results from the Women's Health Initiative Randomized Controlled Trial in The Journal of the American Medical Association. In the article, the authors report on the Women's Health Initiative, which was a study initiated by the National Institutes of Health to determine the effects of hormone therapy in postmenopausal women, or women whose menstrual cycles have stopped, from the ages of fifty to seventy-nine. The researchers attempted to determine if a link existed between a common type of hormone therapy, a combination of estrogen and progestin, and prevalent diseases in postmenopausal women, including cardiovascular disease and cancer. As reported by the authors in their article, the researchers discontinued the study after five years when they found that there were many risks associated with the use of estrogen plus progestin hormone therapy, including increased risks of breast cancer and heart diseases.

In the early 1920s, researchers Edgar Allen and Edward Adelbert Doisy conducted an experiment that demonstrated that ovarian follicles, which produce eggs in mammals, also contain and produce what they called the primary ovarian hormone, later renamed estrogen. In their experiment, Doisy and Allen extracted estrogen from the ovarian follicles of hogs and proved that they had isolated estrogen by using a measurement later renamed the Allen-Doisy test. Allen and Doisy’s 1923 experiment to isolate estrogen showed it was made within the ovaries and also established a method for isolating the sex hormone. That method provided a basis for future research on hormones. Later researchers showed that estrogen functions in the menstrual cycles of primates by signaling for the tissue lining the uterus (endometrium) to thicken in preparation for possible implantation of a fertilized egg.