In the United States, most people are assigned both a biological sex and gender at birth based on their chromosomes and reproductive organs. However, there is an important distinction between biological sex and gender. Biological sex, such as male, female, or intersex, commonly refers to physical characteristics. Gender refers to the socially constructed roles, behaviors, and actions people take on, usually in relation to expectations of masculinity or femininity. As of 2022, there is disagreement over the relation between sex and gender. People’s biological sex and gender greatly influence the way they understand themselves, as well as how others treat them and how they interact with society. Moreover, some people’s gender differs from what they were assigned at birth, and they face discrimination, harassment, and violence. Evolving understandings of gender and sex in the US have created more ways for people to live and express their gender identities.

In the mid-1960s, psychologist John Money encouraged the gender reassignment of David Reimer, who was born a biological male but suffered irreparable damage to his penis as an infant. Born in 1965 as Bruce Reimer, his penis was irreparably damaged during infancy due to a failed circumcision. After encouragement from Money, Reimer’s parents decided to raise Reimer as a girl. Reimer underwent surgery as an infant to construct rudimentary female genitals, and was given female hormones during puberty. During childhood, Reimer was never told he was biologically male and regularly visited Money, who tracked the progress of his gender reassignment. Reimer unknowingly acted as an experimental subject in Money’s controversial investigation, which he called the John/Joan case. The case provided results that were used to justify thousands of sex reassignment surgeries for cases of children with reproductive abnormalities. Despite his upbringing, Reimer rejected the female identity as a young teenager and began living as a male. He suffered severe depression throughout his life, which culminated in his suicide at thirty-eight years old. Reimer, and his public statements about the trauma of his transition, brought attention to gender identity and called into question the sex reassignment of infants and children.

In the book Your Baby’s Sex: Now You Can Choose, David Michael Rorvik and Landrum Brewer Shettles describe methods that couples can use prior to and during conception that will increase the chances of producing a child of their desired sex. Rorvik, a science writer, and Shettles, an obstetrics and gynecology researcher and physician, co-wrote the book. Shettles developed the methods detailed in the book during the 1960s. Although the authors claim a high success rate, some researchers have contested the validity of the methods proposed in Your Baby’s Sex: Now You Can Choose. Despite contradicting evidence for the effectiveness of the methods, the book itself has remained popular throughout its forty consecutive years in print. Since its original publication, Your Baby’s Sex: Now You Can Choose has reached a large audience, with over 1.5 million copies of the book sold worldwide, while adding to the controversy about the ethics of sex selection research.

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.

Hermaphrodites and the Medical Invention of Sex, by historian of science Alice Domurat Dreger, was published in 1998 by Harvard University Press. In the book, Dreger describes how many doctors and scientists treated human hermaphrodites from the late nineteenth century to the early twentieth century. She states that during this time period, many physicians and scientists struggled to determine the nature sex, and to support a classification of sex as male or female, many physicians and scientists resorted to viewing a person's gonads for identification of his or her sex. At the time that this book was published, Dreger was a faculty associate at the Center for Ethics and Humanities in the Life Sciences at the College of Medicine, University of Michigan, Michigan.