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.

Between 1958 and 1962, physicians Olive W. Smith, George V. Smith, and Robert W. Kistner performed experiments that demonstrated the effects of the drugs MER-25 and clomiphene citrate on the female human body. MER-25 and clomiphene citrate are drugs that affect estrogen production in women. At the time of the experiment, researchers did not know which organ or organs the drugs affected, the ovaries and/or the anterior pituitary gland. To determine that, the physicians reviewed nine of their own previous studies in women in which they measured the urinary output of hormones after the administration of either drug. Based on their examination the researchers concluded that MER-25 appeared to influence the anterior pituitary gland in the brain to produce a response in the ovaries and that clomiphene citrate appeared to act on the ovaries. Their results provided early evidence about the mechanisms of both drugs. Later, clomiphene citrate became a common fertility drug.