Androgen Insensitivity Syndrome (AIS) is a human disorder in which an individual's genetic sex (genotype) differs from that individual's observable secondary sex characteristics (phenotypes). A fetus with AIS is genetically male with a 46,XY genotype. The term 46,XY refers to the chromosomes found in most cells of the fetus. Most cells have a total of 46 autosomes, or non-sex chromosomes, and a pair sex chromosomes, XX for genetic females, or XY for genetic males. Due to a defect on the androgen receptor gene (AR) located on the X chromosome, a fetus with AIS cannot process male sex hormones or androgens. The effect on the fetus is that, compared to genetically male fetuses without AIS, it doesn't develop normal male phenotypes. The resistance to androgens affects all of the fetus's organs during embryonic development and during puberty. Although genetically male, persons with AIS can be socially raised as either female or male (sex-of-rearing) yet identify with a gender discordant with their sex-of rearing. AIS and other states of intersexuality challenge physicians, scientists, and society to evaluate definitions of sex.

Amenorrhea is considered a type of abnormal menstrual bleeding characterized by the unexpected absence of menstrual bleeding, lasting three months or longer. Menstrual bleeding typically happens approximately once a month when blood and endometrial tissue, or tissue lining the inside of the uterus, sheds from the uterus through the vagina. Menstruation is expected to stop with pregnancy, breastfeeding, and menopause, or the natural cessation of the menstrual cycle at an older age. However, women may also experience amenorrhea because of an underlying health condition, including low body weight or polycystic ovarian syndrome, that may complicate fertility and contribute to decreased quality of life. According to the American College of Obstetricians and Gynecologists, one in twenty-five women experience amenorrhea as a menstrual disorder within their lives at times.

Charles Raymond Greene studied hormones and the effects of environmental conditions such as high-altitude on physiology in the twentieth century in the United Kingdom. Green researched frostbite and altitude sickness during his mountaineering expeditions, helping to explain how extreme environmental conditions effect respiration. Greene’s research on hormones led to a collaboration with physician Katarina Dalton that culminated in the development of the theory that progesterone caused premenstrual syndrome, a theory that became the basis for later research on the condition. In his later career Greene formed the Thyroid Club of London that brought together specialists in the emerging field on endocrinology. Greene’s research on progesterone and thyroid helped researchers study how of the endocrine system functions in women’s reproductive health.

Polycystic ovarian syndrome or PCOS is one of the most common reproductive conditions in women, and its symptoms include cystic ovaries, menstrual irregularities, and elevated androgen or male sex hormone levels. During the 1930s, Irving Freiler Stein and Michael Leventhal identified the syndrome and its symptoms. Women who experience symptoms of PCOS may also experience secondary symptoms, including infertility and diabetes. Though estimates vary and the causes of the syndrome are not clear as of 2017, PCOS affects approximately ten percent of women of reproductive age. Women who suspect they have symptoms of PCOS should see a doctor, as early treatment may help prevent long-term implications such as infertility, diabetes, and some types of cancers.

In 1989, physicians Henk Asscheman, Louis J. G. Gooren, and P.L.E. Eklund published the article “Mortality and Morbidity in Transsexual Patients with Cross-Gender Hormone Treatment,” hereafter “Mortality and Morbidity,” in the journal Metabolism. The authors presented clinical data regarding patients with gender dysphoria who were actively undergoing gender-affirming hormone replacement therapy. The data highlighted frequencies of various side effects of the treatment, including high blood pressure, blood clots, mood changes, as well as varying risk percentages of osteoporosis and cardiovascular disease, as those side effects are typically common in conventional hormone replacement therapy. According to “Mortality and Morbidity,” few scientists were studying the long-term effects of estrogen and androgen treatment for transgender people at the time of publication. The retrospective study was one of the first to research the long-term effects of hormone treatments on transgender individuals and found health concerns, such as more frequent blood clots and weight gain, in those undergoing gender-affirming hormone treatment.