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.

Eugen Steinach researched sex hormones and their effects on mammals in the late nineteenth and early twentieth centuries in Europe. He experimented on rats by removing their testicles and implanting them elsewhere in their bodies, and he found that the testes interstitial cells produce male sex hormones. He developed the Steinach Rejuvenation Procedure, which he claimed could rejuvenate men by increasing their production of sex hormones. Steinach’s work on female sex hormones and on ovarian extracts led to the development of the first standardized injectable estrogen. Steinach’s research on reproductive hormones helped researchers explain the roles of sex hormones and develop hormone drugs.

In the early twentieth century US, Jean Paul Pratt and Edgar Allen conducted clinical experiments on women who had abnormal menstrual cycles. During the clinical tests, researchers injected the hormone estrogen into their patients to alleviate their menstrual ailments, which ranged from irregular cycles to natural menopause. The hormone estrogen plays a prominent role in the menstrual cycle by signaling the tissue lining the uterus (endometrium) to thicken in preparation for possible pregnancy. In their clinical tests, Pratt and Allen showed that injecting estrogen into female human subjects restored their normal menstrual cycle, removed symptoms such as hot flashes, and caused uterine tissue to grow. The clinical tests conducted by Pratt and Allen provided experimental evidence and justification for the injection of isolated estrogen in women to alleviate, for a short amount of time, different menstrual problems, and it contributed to later hormone therapy research.

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.