Welcome to the fifth installment of our series chronicling the history of the birth control pill. In the previous installment, Margaret Sanger and Katharine McCormick envisioned and bankrolled the development of the birth control pill. Now it had to be tested in large-scale trials.
John Rock, Gregory Pincus, and Min-Chueh Chang had collaborated in the Pill’s development; now it was time to conduct clinical trials. The first study observed 60 women, some of whom were infertility patients while others were nurses. These small trials involved daily temperature readings, vaginal smears, and urine samples, as well as monthly endometrial biopsies. Although the initial results seemed promising, the sample size was small and few of the subjects complied with the protocol.
The approval of the Pill in 1960 marked a turning point in our history.
More test subjects were needed. At this point, historians’ accounts differ. Elaine Tyler May claims that, unable to locate an acceptable pool of volunteers, the researchers tested the Pill on subjects who could not give their consent, such as psychiatric patients. According to Bernard Asbell, however, Rock was scrupulous when it came to informed consent, despite it not being a legal requirement — or even much of a concept at all at this time in history.
Willing participants notwithstanding, conducting such trials in the United States posed a challenge, due to laws against contraception. So the first large-scale clinical trials were conducted in Puerto Rico in 1956. Puerto Rico was densely populated and there was a high demand for alternatives to permanent sterilization, which was widespread on the island due to funding from a wealthy eugenicist named Clarence Gamble, who advocated sterilization for the world’s poor. The clinical trials in Puerto Rico were conducted by Drs. Edris Rice-Wray and Adaline Sattherthwaite; the brand of birth control pill tested was named Enovid. Volunteers were so easy to come by that some clinics had waiting lists.
Test subjects’ health was meticulously monitored. Side effects included nausea, headaches, and dizziness, reported by 17 percent of volunteers. Rice-Wray considered these side effects to be unacceptable, even though the Pill proved completely effective in preventing pregnancy. Rock and Pincus, however, did not think these symptoms were alarming — Pincus, for his part, claimed that they were psychosomatic. In any case, the side effects may have been responsible for many subjects dropping out of the study, always a problem in clinical trials. According to May, others dropped out of the study under pressure from “priests and disapproving husbands,” and there was some concern that “Nordic whites” were using “the colored races as ‘guinea pigs.’”
In 1956, data on 221 subjects had been collected. The report stated, “Enovid gives one hundred percent protection against pregnancy in 10-milligram doses taken for twenty days each month … However, it causes too many side reactions to be acceptable generally.” Rock wondered if the side effects were actually nocebo effects — a phenomenon in which the expectation to experience side effects makes a subject more likely to notice or experience these side effects. A placebo-controlled trial seemed to confirm this, as 17 percent of subjects in the placebo group reported side effects, compared to the 6 percent of subjects who experienced side effects in an experimental group to whom no warning about side effects was given. It is interesting that being given advance warning of possible side effects correlated with an increased chance of experiencing these side effects, and shows how our expectations can shape our experiences.
Test groups were composed of mothers who were for the most part less than 40 years of age, and those who took the Pill as instructed did not get pregnant. After a propaganda campaign by a Catholic group, 10 percent of subjects dropped out of the study, and all of them became pregnant soon after. These dropouts were tracked, and their subsequent babies were examined to ensure that earlier use of the Pill did not have consequences for offspring. The sex ratio was evenly divided between male and female, and infant health was fine.
All told, the trials spanned three countries with more than 20,000 test subjects. Clinical trials in Puerto Rico and Haiti saw 1.7 pregnancies for every 100 women per year. Another field trial in Mexico City reported a failure rate of 0.6. In 1957, the Pill was approved as a treatment for “various gynecological disorders” (such as infertility and menstrual disorders), after which its developers sought to have it approved as a contraceptive.
The FDA began to investigate the Pill’s safety. While most physicians surveyed found the Pill to be “safe and effective for short-term use in treating gynecological problems,” there were some dissenters, including Dr. Edward Tyler, a researcher and head of the Planned Parenthood Clinic in Los Angeles. He was concerned about the Pill’s safety, as the side effects had been, in his experience, often severe: abnormal bleeding, weight gain, fluid retention, and more. In 1958, an FDA official heard Tyler’s concerns at a meeting. Because Tyler was considered to be a more neutral source than either Rock or Pincus, his concerns were given a lot of weight, and the approval process was slowed.
Eventually, however, in 1960 the Pill was approved as a contraceptive. Due to lingering concerns about the safety of long-term use, prescriptions were limited to two years. But 1960 marked an incredible turning point in our history — able to control their reproductive destinies, people with uteruses could choose their family sizes, choose not to have children at all, and have easier access to higher education and find futures in the labor force. Truly, thank goodness for the Pill!
Stay tuned for the next installment of this series, in which we learn about the people whose invisible labors provided the raw material for hormonal contraceptives. Mexican peasants were integral to the synthesis of progesterone, and some say they were exploited.