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"Pincus Pills." Probably no single name will be forever linked with the pills, as is Jenner's with vaccination. The search for medically useful knowledge nowadays goes along parallel lines at many places, often with a team working at each center. But Physiologist Gregory Pincus of the Worcester Foundation for Experimental Biology and Gynecologist John Rock of Harvard University rate high among the pioneers of oral contraception. It was at Harvard, too, that Dr. Fuller Albright noted in the mid-1940s that an excess of estrogen* in the bloodstream soon after the end of menstruation somehow prevented ovulation. A few years later, Pincus and Rock were working together to find a way of helping subfertile women ovulate, and thus conceive. They first had to regularize the woman's cycle, and they hit upon a synthetic progestin chemically akin to another female sex hormone, progesterone. The progestin, taken for 20 days in mid-menstrual cycle, suppressed ovulation by simulating pregnancy. Taken off the medicine, the women had a more normal cycle, with surer ovulation. After Pincus and Rock had produced a gratifying number of conceptions, a new idea struck them: Why not use the progestin deliberately to suppress ovulation every monthin other words, as a contraceptive?
At first the drug worked well. Several days after a woman stopped taking it, she had what seemed like a normal but mild menstrual period. There were few side effects. But as the drug was further purified, Dr. Rock began to hear patients complain of too much "breakthrough bleeding" in mid-cycle. Analysis showed that the purified drug contained no detectable estrogen. Apparently estrogen, even in the most minute quantity, prevented some side effects, including unwanted bleeding. So when Chicago's G. D. Searle & Co., which had worked closely with Pincus and Rock, began making "the Pincus pills" as Enovid in 1957, the formulation contained 66 parts progestin to one part estrogen. The progestin dose has been reduced by as much as 90% in Searle's newest pills, Ovulen, but the combination principle is the same.
Other hormone investigators took a different direction, concentrating on the rediscovered, though still not fully understood, powers of estrogen. From the fifth to the 20th day of a normal woman's cycle, her estrogen level is fairly steady, except for a dip at the time of ovulation. If they could prevent this dip, the researchers reasoned, they could prevent ovulation. They felt it would be more natural to do this by providing nothing but added estrogen until the 20th day, and then giving progestin only briefly. San Antonio Researcher Dr. Joseph W. Goldzieher worked with Syntex Laboratories to develop the resulting "sequentials." Beginning with Day 5, the woman takes a white estrogen pill for 15 days, then a distinctively colored