The Pill That Changed Everything and the Women It Didn't Protect

Few medical innovations have shaped modern life as profoundly as the combination birth control pill. Since its FDA approval in 1960, it has given millions of people the ability to choose if and when they want to become pregnant. But the story of how the pill works, and how it came to be, demands a more complete telling.

Because while the pill marked a breakthrough in reproductive autonomy, its invention was built, quite literally, on the backs of marginalized women.

How the Pill Outsmarts the Menstrual Cycle

The combination birth control pill is a master of biological misdirection. At first glance, it mimics the body’s natural hormones: estrogen and progesterone. But beneath the surface, it rewires the entire reproductive rhythm.

Each month, in a typical cycle, the brain and ovaries engage in a finely tuned conversation. The hypothalamus, located deep in the brain, releases pulses of gonadotropin-releasing hormone (GnRH), which act like signals over a loudspeaker. These pulses instruct the pituitary gland to release two key hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH encourages ovarian follicles to grow and mature. As estrogen levels rise in response, LH surges, triggering ovulation: the release of a single egg from the ovary.

The pill intentionally disrupts this chain reaction. When taken daily, it floods the body with steady levels of synthetic estrogen and progestin. This artificial hormone environment shuts down the pulsatile signaling from the brain. It is like putting the hypothalamus and pituitary on mute.

With FSH suppressed, ovarian follicles don’t develop. With LH suppressed, there is no mid-cycle surge, and no egg is released. The ovary stays quiet. No ovulation means no pregnancy.

But the pill doesn’t stop at ovulation. It works on multiple fronts. The synthetic progestin causes the cervical mucus to become thicker and more viscous, transforming it from a welcoming fluid into a physical barrier that traps sperm before they can reach the uterus. Meanwhile, the endometrial lining, the soft tissue that would normally thicken to receive a fertilized egg, remains thin and inhospitable.

These changes are reversible. When the pill is stopped, the body’s natural cycle typically resumes. But as long as the daily hormonal signal continues, the pill keeps the reproductive system in a controlled, quieted state.

In short, the combination pill uses the body’s own hormonal blueprint, then subtly rewrites it. Not by overpowering the system, but by whispering a new set of instructions just loud enough to override the originals.

How the Pill Was Made

The origin story of the pill begins not in a lab, but in the wild. In the 1940s, chemist Russell Marker discovered that a particular Mexican yam, the Dioscorea Mexicana, contained diosgenin, a compound that could be chemically converted into progesterone. It was a plant with pharmaceutical potential hidden in its roots.

With diosgenin in hand, labs could mass-produce synthetic hormones for the first time. This breakthrough launched a race to develop an oral contraceptive that could reliably suppress ovulation without requiring surgery or long-term hospitalization.

The effort brought together unlikely collaborators. Gregory Pincus, a reproductive biologist known for his work on in vitro fertilization, Dr. John Rock, a Catholic obstetrician-gynecologist who believed in the moral necessity of family planning, formed the scientific core, and Margaret Sanger, the birth control activist who founded Planned Parenthood provided the vision and the funding.

Together, they developed early prototypes of a hormonal contraceptive pill. In animal studies, repeated injections of progesterone had reliably halted ovulation. The next step was to find out if it would work in women.

The Puerto Rico Pill Trials

Initial testing began in 1954 at the Worcester State Mental Hospital in Massachusetts. Sixteen women, all psychiatric patients, were given early versions of the pill containing extremely high doses of progesterone. Their ovaries and uteruses were surgically examined afterward to determine if ovulation had been blocked. With such high doses of progesterone, it is no surprise, that it worked. Today, such methods would be considered extremely unethical. But at the time, they were just the beginning...

With their success in the State Mental Hospital, research moved to Puerto Rico. There, laws were more permissive, birth rates were high, and researchers faced fewer legal and regulatory barriers. But these advantages came at a moral cost.

In 1955, the first study recruited 20 female medical students at the University of Puerto Rico. More than half dropped out due to side effects like nausea, dizziness, and headaches. To minimize the risk of pregnancy during trials. Small amounts of synthetic estrogen, were added to the progesterone only pill, giving birth to the combination birth control pill. From here research moved to Rio Piedras, Puerto Rico. 265 women from the community were enrolled to test the prototype combination pill, marketed as Enovid. It was 100 percent effective at preventing pregnancy when taken correctly, but 22 percent of participants withdrew due to side effects, which remained severe throughout the trials.

Complaints were dismissed. Follow-ups were rare. Most troubling, the participants were never fully informed of the risks. The study design prioritized scientific proof over individual safety. The researchers chose Puerto Rico not just for legal ease but for the assumption that poor, nonwhite women would be more "available" and "naive" for experimentation.

What Changed and What Hasn’t

When Enovid was finally approved by the FDA in 1960, it delivered hormone levels far higher than necessary: 10,000 micrograms of progestin and 150 micrograms of estrogen per dose. Today’s combination pills contain much lower amounts, typically 100 to 150 micrograms of progestin and 20 to 35 micrograms of ethinyl estradiol.

Lower doses have improved side effects, but hormonal contraception still carries risks. It can increase the likelihood of blood clots, stroke, or hypertension in some users, particularly smokers or those with underlying conditions. At the same time, the pill has proven benefits. It reduces menstrual pain and heavy bleeding, improves symptoms of endometriosis and polycystic ovary syndrome (PCOS), and decreases the risk of certain reproductive cancers.

The pill also paved the way for an entire ecosystem of hormonal birth control methods: intrauterine devices, vaginal rings, implants, and injectables. Each owes its existence to that original formulation. It was the first time medicine offered a systemic, non-surgical way for women to control if and when they became pregnant.

It was revolutionary. But some revolutions come with consequences.

Looking Ahead

The combination pill transformed the landscape of reproductive health. It gave millions of people the ability to shape their lives with more autonomy. But its development rested on a foundation of inequality.

The women who participated in early trials, many poor, many brown, many silenced, did not receive the same freedom the pill would later provide to others. Their pain was minimized. Their agency was denied. And their role in one of the most consequential medical advances of the 20th century is too often erased.

Reproductive research today must do more than innovate. It must reckon. Informed consent, participant protection, and health equity are not side notes to scientific progress. They are its foundation.

As historian Gabriela Soto Laveaga reminds us, "Our obligation as regular citizens is to be informed, to know the history, and to ask the questions. If we have a baseline of knowledge, it’s easier to contend, not forget, make it public, and acknowledge when mistakes have been made."

And if you work in the sciences, it is not enough to know this history you have to carry it forward. Innovation cannot come at the expense of the vulnerable. We owe it to those women, and to future generations, to do better. The future of science must be built not just on discovery, but on dignity.

Scientific progress is only truly meaningful when everyone has the dignity to benefit from it, not just the power to survive it.