Enovid: The First Hormonal Birth Control Pill (1957–1988)

Editor’s note: this article replaces a previous article on Enovid published 20 January 2009.

In 1960, the US-based pharmaceutical lab G.D. Searle and Company, or Searle, launched Enovid, one of the first oral birth control pills, following approval by the US Food and Drug Administration, or FDA. Prior to Enovid, there were no oral birth control options for women. Women were reliant on male condoms, homemade concoctions, and other contraceptive methods as barriers to provide them with protection against pregnancy. Women’s rights activists like Margaret Sanger aimed to address that gap by supporting the creation a birth control pill. Sanger collaborated with researchers to formulate a hormonal pill that gives women the ability to protect themselves against getting pregnant. Although some steps in the path to creating the pill were unethical by today’s standards, they did result in the creation of an oral birth control pill. Enovid offered a new method of family planning that gave women the ability to control pregnancy and served as a precursor to additional birth control pills, which over 150 million women use worldwide annually.

1. Motivations for Creating Enovid
2. Development of the Pill
3. The Start of Clinical Trials
4. Enovid on the Market
5. Birth Control After Enovid

Motivations for Creating Enovid

A variety of factors led to the creation of Enovid. During the Great Depression, which lasted from 1929 to 1941, poverty and starvation were widespread problems in the US. Unemployment was the highest it had ever been in US history. Over twelve million people were jobless. During a time of extreme uncertainty and joblessness that plagued millions of families in the US, having smaller families was seen as a strategy to combat poverty, as a smaller family would increase the number of resources available for each child. However, many women were unable to take their own precautions to lower the risk of pregnancy, as laws regarding buying contraceptives varied across states. That incentivized the creation of Enovid to give women control over reproduction.

Prior to Enovid, most previous birth-control methods were difficult to use or male-centered. The late 1920s through the early 1940s were a time when the most common type of family planning method available were male condoms, cervical caps, rubber diaphragms, and homemade concoctions. Male condoms are made from perishable rubber materials. Cervical caps and rubber diaphragms fit in a woman’s cervix. At the time, both options were often expensive and uncomfortable for some women. Intrauterine devices, or IUDs, are a contraception method that scientists developed in the early twentieth century, which doctors insert into the uterus, where IUDs remain for over five years. Women also used Lysol disinfecting douches to spray into their vaginas to kill sperm after intercourse. Brands advertised douches, like other contraceptive methods, during the 1930s through the 1960s, as a female hygiene product instead of a contraceptive for women. However, women used them as contraceptives. The chemicals in the douches were ineffective and mostly harmless, but could cause burns if users did not dilute the solution enough. Contraceptives were often illegal in many states at the time, so women had no option to control their pregnancy unless the product was a menstrual or hygiene product. Some of those contraceptive methods failed to provide women with preventive measures for pregnancy because they were ineffective and posed unforeseen risks, which demonstrated the need for women to have safer, women-centered options for birth control.

Another factor shaping discussions about birth control at the time was the eugenics movement, which encouraged reproduction by particular individuals and discouraged reproduction by others and which was gaining popularity and support in the early to mid-twentieth century. That movement became another motivation to develop a feasible birth control option. Eugenicists supported the development of an oral birth control pill as a method to control who can reproduce and how. Sanger, in addition to being a women’s rights and birth control activist, was also a supporter of the eugenics movement. She aided in the creation and legalization of birth control for women through lobbying, protests, and publishing projects. Sanger used both the eugenics movement and her feminist activism to advocate for birth control methods and make them available to women of all socioeconomic statuses. The eugenics movement’s concern about the reproduction of the unfit and Sanger's advocacy for women-centered contraceptives motivated the creation of Enovid as both a means for some women to be able to prevent their own pregnancy, but also as a way to limit reproduction amongst the poor, disabled, and those incarcerated.

Development of the Pill

In the 1950s, Gregory Pincus, a researcher who conducted studies on fertility and hormones, met with Sanger about the development of a birth control pill, then sought to collaborate with other scientists who studied estrogen and progesterone to develop it. Estrogen and progesterone are hormones produced by the ovaries that regulate the female reproductive system and early pregnancy. Pincus’s studies on impregnation in rabbits in 1934 led to his investigation of hormone regulation relating to pregnancy and ovulation. In 1951, Pincus and Min-Chueh Chang, a researcher who studied animal physiology and artificial insemination at Cambridge University in Cambridge, United Kingdom, began studying progesterone as a possible contraceptive hormone in a birth control pill. That experiment confirmed that repeated injections of progesterone prevented ovulation from occurring in the tested animals, thus demonstrating its contraceptive-like effects.

During that time, other researchers were creating synthetic progesterone, which made the compound more accessible. In 1951, Carl Djerassi, a researcher who studied hormones and steroids in Mexico City, Mexico, developed a synthetic hormone called norethindrone, which was a strong progestin, or a synthetic form of progesterone. Researchers knew that orally taking more natural progesterone weakened its activity in the body, so they worked on creating synthetic forms. Norethindrone stops ovulation from occurring and changes the cervical lining. Following that invention, in 1953, a researcher named Frank Colton, who studied biochemical structures and usages of steroids, created the hormone norethynodrel at Searle. Norethynodrel, like norethindrone, offers a potent and lab-replicable hormone that is more effective at preventing pregnancy than natural progesterone. Norethynodrel differs from norethindrone in that the double bond placement in the structure also has more applications, such as providing relief for acne. Following the inventions of norethynodrel and norethindrone, Pincus and Chang began experiments using those hormones individually. For their birth control pill, Pincus, however, decided to use norethynodrel in the formulation of Enovid.

The Start of Clinical Trials

Pincus reached out to John Charles Rock, an obstetrician and gynecologist in Boston, Massachusetts, about collaborating to conduct trials of the new birth control pill, starting in 1953. Pinus and Rock began their trials with Rock’s patients at the Free Hospital for Women in Boston. Their first study enrolled twenty-seven patients for a three-month trial. The pills only contained high levels of progesterone, around 250 to 300 mg, and each patient received three weeks of pills. The study grew to include sixty patients from the Free Hospital for Women and other clinics within its first year. The women took their own temperatures, vaginal smears, and collect urine for analysis. Half of the women eventually dropped out of the study due to the study’s demands or harmful side effects. Searle and Katharine McCormick, a nurse and Sanger’s friend, funded the trials and research.

Pincus continued trials at Worcester State Hospital, a mental health facility in Worcester, Massachusetts, for both men and women in 1954. Mental asylum trials at the time did not require the collection of permissions or consent from patients. McCormick, a women’s rights activist who collaborated with Sanger and funded much of the research process, offered money to renovate the hospital to the directing physician, Bardwell Flower, in exchange for the ability to conduct the study there. The study enrolled sixteen women and sixteen men, all of whom the institution deemed psychotic. The participants did not know they were in a study, did not receive any disclosures of side effects or risks, did not give informed consent, and received various doses of estrogen and progesterone unknowingly. Also, in 1954, Pincus began trials with a new group of artificially created progestin, much stronger than natural progesterone. The two drugs were norethindrone, which Syntex created, and norethynodrel, which Searle created. Pincus and Rock proceeded with using the Searle drug. Searle sent the drug in unlabeled containers. In 1955, Rock reported to Searle that progestin delayed ovulation, which meant it stopped the release of hormones that signaled the ovaries to release eggs. Researchers dropped the male side of the study due to inconsistent results.

Following the Worcester study, Edris Rice-Wray, the medical director of Puerto Rico’s Family Planning Association, aided in conducting birth control trials with Pincus in Puerto Rico, starting in 1956. Previously, Pincus travelled to Puerto Rico in 1954 and saw legal birth control clinics in operation. Pincus reported his findings to McCormick and, with her funding, and Rice-Wray, started trials. Rice-Wray and her team recruited 100 women to test the new pill and had 125 control patients. The women in the study only knew they were taking a new contraceptive that prevents pregnancy, but had little to no knowledge that the drug was experimental or of the possible side effects associated with high levels of progestins and estrogen. Researchers told the women in the control group they were enrolled in a survey to study family size. The team used Searle’s compound, norethynodrel, and gave participants a bottle of twenty days of pills and instructions to take one pill a day and wait five days before starting a new bottle of pills. Instructions were difficult to relay, however, and many mistakes occurred. Many women dropped out due to intense side effects or social pressures. During those early stages of development, Enovid had extremely high doses of only progestin, which can cause side effects such as heart attacks, blood clots, double vision, and many other severe conditions. When Puerto Rican women reported feeling side effects, the scientist disregarded their claims and continued to provide women with the drug and collect data. Of the original 225 women, thirty-eight of the women in the study experienced negative reactions such as nausea and random spotting of blood despite not having a period. During the continuation of the study, twenty-five women withdrew specifically due to the side effects they experienced.

At the end of 1956, Rice-Wray and Pinus presented the data from the Puerto Rican trials to Searle and continued additional trials before submission to the FDA. Pincus reported that seventeen women of the original 221 from the trial experienced pregnancy due to improper use of the drug, rather than a failure of the drug itself. Searle had already patented norethynodrel by that time and trademarked the name Enovid for the birth control drug. In 1957, Pincus ran a series of experiments to observe whether side effects from Enovid were mental. He created three groups. The first group learned about the drug and its side effects. Researchers gave the second group a placebo and informed them about the side effects. Researchers gave the third group the drug and did not inform them about the side effects. The second group experienced side effects, and the third group experienced very few side effects. Pincus reported that the results showed that the drug itself did not cause many of the side effects. At the conclusion of the study in 1957, there were no reported pregnancies in 1,297 menstrual cycles in 130 women.

Pincus connected with Clarence Gamble, a doctor who graduated from Harvard University Medical School in Boston, Massachusetts, and agreed to fund a second trial in Puerto Rico. Gamble hired people to recruit women through various methods, such as going door to door in a crowded and poor area of Puerto Rico, offering birth control options for women who were previously refused sterilization at hospitals. Pincus also began trials in Haiti. Then, around midway through the experiments in Puerto Rico and Haiti, Pincus and Chang found that the hormone sample had been accidentally mixed with a synthetic estrogen at an unknown time. The combination has been proven to have fewer side effects and work more effectively. According to Erin Blakemore, a journalist based in Boulder, Colorado, and the Planned Parenthood Foundation, the Enovid trials do not adhere to the ethics and safety research standards as of 2025. Blakemore regarded the experiment as unethical due to the lack of informed consent provided, along with the neglect shown towards completing autopsies of two participants who died during the trial. Despite the trials being conducted unethically, the data from those trials confirmed that Enovid functions as a treatment for reproductive disorders and as a contraceptive, leading to it gaining FDA approval and entering the market.

Enovid on the Market

In 1957, the FDA approved Enovid, the brand name for the birth control pill, for infertility and irregular period treatments only. Also in 1957, Enovid was sold as Enavid in England. Then, in July of 1959, Searle filed for Enovid to be marketed for contraceptive purposes as well. However, at the time, the sale of contraception remained illegal in many states until the Supreme Court case Griswold v. Connecticut (1965) legalized its sale to married women throughout the country. In the summer of 1960, Enovid received approval from the Food and Drug Administration to be marketed as the first oral birth control pill. By 1965, over five million women in the US used Enovid. In the US, the pill was initially prescribed only to married women, as sales to unmarried women were illegal in many states. However, in 1972, the Supreme Court decided to legalize the sale of contraceptives to unmarried women as well in the court case Eisenstadt v. Baird (1972).

After the launch of Enovid in 1960, Pincus, with Searle, developed another version of Enovid called Enovid-E in 1964 that contained lower hormone levels, was cheaper, and reduced the amount of side effects in users. The alternative pill also came at a lower cost to consumers and offered those sensitive to the original hormone mix a chance to use a pill with a lower dosage. In 1967, Time magazine featured the pill as a means for liberating and changing family planning and sex in the US. Enovid and Enovid-E were gaining traction in the US and started to face more publicity as well as scrutiny by scientists.

Searle also went on to launch Enovid in the UK as well, under the name Conovid in the early 1960s. Conovid has half as many milligrams of hormones as Enovid did. Although Searle did not require approval from the British market, the British Family Planning Association performed tests on the drug. During that time, that association was responsible for teaching healthcare providers about birth control and scrutinizing any birth control options prior to them being on the market. However, after cases of severe blood clots that led to the death of one person in Britain and two Americans, along with some birth defects, the European market removed Conovid by the end of the 1960s.

From the 1960s through the 1970s, Searle began facing many lawsuits over Enovid. Users accused Searle of the pill causing blood clots, thrombosis, and other side effects in users. A lawsuit filed in 1975 focused on two women in Los Angeles, California, in 1961, who were taking Enovid and died from pulmonary embolisms, which are blood clots in parts of the body such as the lungs. By 1963, researchers such as Laurence Pilgeram, who studied biochemistry at the University of Minnesota in Minneapolis, Minnesota, found that Enovid caused changes in clotting factors that prevented blood clots, and recommended that Searle take Enovid off the market until further research occurred. Other researchers found concurring results with Pilgeram's, finding that Enovid users were nine times more likely to have blood clot disorders. However, Enovid remained on the market until the FDA discontinued its use in the US in 1988.

Birth Control After Enovid

Since the discontinuation of Enovid, many labs have created new versions of the pill, such as Brevicon and Ocella, which are combination drugs with estrogen and progestin, and which are still available to women in the US as of 2025. Those birth control pills contain a lowered hormone mixture of more potent progesterone and estrogen. Lowering the amount of estrogen and progesterone lessens the intensity of the side effects experienced by high-level progesterone birth control pills such as Enovid. Birth control pill options as of 2025 still carry side effects similar to Enovid, such as irregular bleeding, weight gain, migraines, mood changes, and more. According to a study by the United Nations, over 150 million women worldwide used birth control pills in 2019.

While the road to the development of Enovid involved practices that most would consider unethical according to medical standards as of 2025, Enovid was one of the first effective method of birth control that gave women the right to control their bodies and have a choice in pregnancy for the first time. Despite Enovid’s discontinuation, researchers have been able to build on the original birth control pill formula to develop safer oral birth control options that millions of women worldwide continue to use.

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