sciencebriefs
13:00in productionCh. 1 · A hormone that blocks ovulation/ 13:00 · ceiling 15 min
Medicine

Combined oral contraceptive pill

1961

Gregory Pincus and John Rock turned a 1950s hypothesis about progesterone into the first oral contraceptive, tested on women in Puerto Rico whose reported side effects were overridden on the way to FDA approval in 1960.

Backed by funding that Margaret Sanger and Katharine McCormick secured for his laboratory, Gregory Pincus worked with Min Chueh Chang to confirm that progesterone could suppress ovulation, then partnered with physician John Rock to test the approach first on infertility patients in Massachusetts and then, at larger scale, on women at birth control clinics in Puerto Rico from 1955. Despite a trial supervisor's report that the drug, sold as Enovid, caused side effects serious enough to be unacceptable, Pincus and Rock pressed ahead, and the Food and Drug Administration approved it for contraceptive use in May 1960. The pill went on to be used by well over 100 million women worldwide, cited widely as a catalyst for broader social change, even as its cardiovascular and cancer risks, weighed against its near-complete effectiveness at preventing pregnancy, remain part of how it is prescribed today.

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Chapters & takeaways6
  1. 0:08
    A hormone that blocks ovulation

    Pincus and Min Chueh Chang confirmed that progesterone could prevent ovulation, the biological basis for a contraceptive pill.

  2. 2:10
    Funding from outside the lab

    Margaret Sanger and Katharine McCormick supplied the introductions and money, including a fiftyfold funding increase from McCormick, that let Pincus scale up the research.

  3. 4:20
    From infertility patients to a mass trial

    John Rock first tested progesterone on infertility patients in Massachusetts before the trial expanded to birth control clinics in Puerto Rico.

  4. 6:30
    A warning that was overruled

    A Puerto Rico trial supervisor reported the drug caused too many side effects to be acceptable even as it fully prevented pregnancy, a concern Pincus and Rock did not accept.

  5. 8:40
    Approval, and a rapid global reach

    The FDA approved the pill in May 1960, and it went on to be used by over 100 million women worldwide.

  6. 10:50
    Why the trial history belongs in the story

    Worth an hour because the pill's enormous social impact and the ethically uncomfortable circumstances of its testing are both part of the same history.

Worth your time?

Yes. Study the whole thing.

4/ 5
What works
  • the concreteness of tracing the money, Sanger's introduction and McCormick's fiftyfold funding increase, behind a discovery usually credited to science alone
  • the direct inclusion of Rice-Wray's side-effect report rather than smoothing over the controversy
  • the effectiveness numbers, set against the risk figures, given plainly rather than rounded to a single reassuring line
What does not
  • it does not resolve how informed the Puerto Rican trial participants actually were about the risks
  • it does not detail the later reformulations that reduced the hormone doses and side effects present in the original Enovid
Study it if
  • readers who know the pill mainly as a symbol of the sexual revolution
  • anyone interested in how contraceptive trials of the 1950s were actually conducted
  • readers who want effectiveness numbers alongside the history
Skip it if
  • readers wanting a purely celebratory account with the trial concerns left out
  • anyone after the detailed endocrinology of the menstrual cycle
The written brief3 min read

A hormone that blocks ovulation

The scientific basis for an oral contraceptive rested on a specific hormonal claim: that progesterone, a hormone the body produces after ovulation, could be given artificially to suppress ovulation before it happened, preventing pregnancy by stopping an egg from being released at all. Gregory Pincus, a biologist who had co-founded the Worcester Foundation for Experimental Biology in Massachusetts, worked with Min Chueh Chang to confirm this effect, establishing progesterone’s ability to block ovulation as the working principle behind what would become the pill. Turning that principle into a usable medicine still required a form of the hormone that worked reliably when taken by mouth and a way to test it safely in people.

Funding from outside the lab

Pincus’s research reached the scale it needed largely because of funding secured from outside conventional scientific channels. Margaret Sanger, the birth control advocate, met Pincus in 1951 and arranged initial support through the Planned Parenthood Federation of America, then introduced him in 1952 to Katharine McCormick, a wealthy suffragist and biologist who, from 1953, increased her funding of the project roughly fiftyfold over what it had previously received. That money let Pincus expand from laboratory work into human trials, beginning with physician John Rock’s tests of progesterone and, later, several progestin compounds on infertility patients in the Boston area in 1953 and 1954.

From infertility patients to a mass trial

The trial then moved to a larger and more vulnerable population: from 1955, Pincus and Rock tested the compound, marketed as Enovid, on women attending birth control clinics in Puerto Rico, a location chosen partly because an established network of roughly 67 clinics already served low-income women there and local conditions around contraceptive testing were less restrictive than on the mainland United States. The Puerto Rico trials, along with subsequent testing in Haiti, Mexico and Los Angeles, provided the data on effectiveness and side effects that would eventually support a case for regulatory approval, gathered from a population with markedly less social and economic power than the Massachusetts patients Rock had studied first.

A warning that was overruled

Edris Rice-Wray, who supervised the Puerto Rico trial, reported that Enovid gave complete protection against pregnancy but caused side effects serious enough, in her judgment, to make it unacceptable for general use. Pincus and Rock disagreed, drawing on comparisons with placebo groups and their experience with patients in Massachusetts, and did not treat her assessment as a reason to halt or substantially redesign the trial. That disagreement, over how much discomfort and risk was an acceptable price for effective contraception, and over how much weight a field researcher’s direct concerns should carry against the judgment of the scientists running the wider programme, was not resolved before the drug moved toward approval.

Approval, and a rapid global reach

The Food and Drug Administration approved Enovid for contraceptive use in May 1960, making it the first oral contraceptive available in the United States. Used correctly, combined oral contraceptive pills of this kind fail to prevent pregnancy in roughly three cases per thousand each year, though typical, less than perfect use raises that failure rate closer to nine per hundred; both figures represented a substantial improvement in reliability over the contraceptive methods most widely available before it. Uptake was rapid and lasting: the pill is now used by well over 100 million women worldwide, remains on the World Health Organization’s list of essential medicines, and is widely credited as a catalyst for broader changes in sexual behaviour and women’s participation in education and work.

Why the trial history belongs in the story

This history is worth understanding as a single, unresolved whole rather than splitting the science from its costs: the same programme that gave millions of women reliable control over pregnancy also ran its largest trial on women with comparatively little power to refuse or fully weigh the risks, and overrode a direct warning about side effects from the researcher closest to the patients. None of that erases the pill’s real and lasting effect on women’s lives, documented in its continued use by over 100 million people and its place among the world’s essential medicines, but it does mean the achievement and the ethical discomfort belong in the same account rather than in separate ones.

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