Metformin hydrochloride, hereafter metformin, is a medication that doctors prescribe to treat type 2 diabetes, a condition where the body fails to respond effectively to the hormone insulin, leading to high blood sugar levels. In 1922, Emil Werner and James Bell, chemists working at Trinity College in Dublin, Ireland, were among the first to synthesize a compound with metformin’s modern chemical formula, namely dimethylbiguanide. At first, physicians didn’t recognize the compound’s ability to lower high blood sugar levels. However, the drug found other uses: physicians prescribed it to treat malaria and flu in the 1940s. Metformin as a treatment for diabetes became popular in the 1990s. In addition to type 2 diabetes, physicians also prescribe metformin to those with polycystic ovary syndrome, or PCOS, as some of its symptoms are similar to those of diabetes. Treating PCOS helps to reduce infertility caused by irregular or no ovulation. Metformin’s wide range of uses has helped hundreds of millions of people across the globe in managing diabetes, but also in treating PCOS and malaria.

In 1935, US-based physicians Irving Freiler Stein and Michael Leo Leventhal published “Amenorrhea Associated with Bilateral Polycystic Ovaries,” hereafter “Amenorrhea,” in the American Journal of Obstetrics and Gynecology based on their clinical experience with seven female patients. In their article, Stein and Leventhal report finding a correlation between a lack of menstruation for a prolonged period, or amenorrhea, in the women and the presence of bilateral polycystic ovaries, in which cysts form in both ovaries. Stein and Leventhal theorize that such cysts form due to hormonal imbalances, which makes their presence indicative of an endocrine, or hormonal, disorder. That explanation contested a widely held belief at the time that inflammation caused amenorrhea. “Amenorrhea” was one of the first publications to propose a hormonal explanation for bilateral polycystic ovaries and to describe the cluster of symptoms that became the basis for diagnosing what later became known as polycystic ovarian syndrome, or PCOS, an endocrine disorder that affects five to eleven percent of women globally per year.