The US Food and Drug Administration, or FDA, published the “Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs,” henceforth “Study of Gender Differences,” in July 1993. The document defined acceptable practices for investigators studying new drugs. Prior to 1993, investigators excluded most women from clinical trials because in 1977, the FDA recommended that anyone who could possibly become pregnant be excluded from early phase drug research to minimize risk to a potential fetus. In 1997, the FDA reversed that guidance, advising investigators to include women in early phase drug research, a decision that reflected changing views about a woman’s ability to decide whether to participate in drug trials and furthering research on the effects of drugs on women.

Thalidomide, a drug capable of causing fetal abnormalities (teratogen), has caused greater than ten thousand birth defects worldwide since its introduction to the market as a pharmaceutical agent. Prior to discovering thalidomide's teratogenic effects in the early 1960s, the US Food and Drug Administration (FDA) did not place regulations on drug approval or monitoring as it later did. By 1962, approximately 20,000 patients in the US had taken thalidomide as part of an unregulated clinical trial before any actions were taken to stop thalidomide's distribution. Due to thalidomide's effects on fetuses, both nationally and abroad, the US Congress passed the 1962 Kefauver-Harris Amendments to the 1938 Food, Drug, and Cosmetic Act. These amendments imposed guidelines for the process of drug approval in the US and required that a drug be safe as well as effective before it could be approved and marketed. Thalidomide also influenced the FDA's creation of pregnancy categories; a ranking of drugs based on their effects on reproduction and pregnancy. Thalidomide motivated the laws on regulating and monitoring drugs developed in the US and by the FDA in the twentieth and twenty-first centuries.

In 2006, the United States Food and Drug Administration, or FDA, published the “Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products,” also called the Physician Labeling Rule, to improve the safety and efficacy of prescription drugs and drug products. Within the Physician Labeling Rule, the FDA includes a section titled “Use in Specific Populations” or Section 8, which refers to drugs used by pregnant women, lactating women, and people of reproductive capacity. The FDA stated that the purpose of the Physician Labeling Rule was to make drug labels easier for physicians to understand and use when prescribing drugs to pregnant women. With the Physician Labeling Rule, the FDA improved patient-physician communication and the safety of drug use during pregnancy.

In 2014, the United States Food and Drug Administration published the Pregnancy and Lactation Labeling Rule to amend previous guidelines for the prescription of drugs for pregnant and lactating women. The 2014 Pregnancy and Lactation Labeling Rule was intended to increase the safety and efficacy of prescription drugs by making drug labels easier for physicians to understand and utilize. The Pregnancy and Lactation Labeling Rule restructured drug labels and required that they include narratives describing drug-associated risks to women and fetuses, rather than using complicated letter categories. The Pregnancy and Lactation Labeling Rule changed the framework for drug labeling, making it easier for doctors to prescribe safe and effective drugs to pregnant women, lactating women, and people of reproductive capacity.

The United States Food and Drug Administration, or FDA, published 'General Considerations for the Clinical Evaluation of Drugs,' in September 1977. The document defined acceptable practices for investigators who studied new drugs. Specifically, the document outlined the common clinical trial methods. Clinical trials are studies to test whether a new drug is safe before doctors can prescribe it to patients. Prior to 1977, the Protection of Human Subjects Rule primarily regulated clinical drug trials, but it did not specify who could and could not be included in clinical trials. In the document, the FDA recommended that anyone who could become pregnant be excluded from early-phase clinical trials to minimize risks to a potential fetus. After the FDA published the document, investigators excluded women from clinical trials. The document ultimately prevented women of reproductive capacity from participating in early phase clinical trials, which affected women’s health research.