Then a major observational study gave the estrogen theory some real traction. For 15 years, the Harvard Nurses Health Study had been tracking the diets, health habits and disease rates of more than 120,000 nurses. When researchers pored over the mountains of data produced by that study, they found a startling statistic: women who took estrogen had a 40% lower rate of heart disease than women who didn't. And women who continued taking estrogen were less likely to suffer a heart attack than women who took it for awhile and then stopped.
You can imagine the research papers and the headlines that resulted. There calls among researchers and doctors alike to start prescribing estrogen to all post-menopausal women who had risk factors for heart disease. More cautious researchers called for a controlled clinical trial before estrogen was given out like heart-healthy candy, and were criticized for it. How could they, in good conscience, deny this obvious wonder drug to millions of women while waiting for long clinical trials to play out?
A pharmaceutical company, Wyeth-Ayerst, eventually funded the clinical trials - hoping, of course, that estrogen would be shown to prevent heart disease. More than 16,000 women were randomized and enrolled in the study. For five years, half received estrogen and half received a placebo.
The results were hardly what Wyeth-Ayerst had expected: The women taking estrogen developed heart disease at a higher rate - 30% higher, in fact. They were also more likely to suffer a stroke . another cardiovascular disease. Later clinical trials confirmed the bad news.
The experts were flabbergasted. The statistical correlation in the Harvard Nurses Study couldn't have been more convincing: women who took estrogen were far less likely to have a heart attack. And it couldn't have been fluke - there were too many subjects involved.
So what happened? Nobody can say for sure, but some researchers at the time offered an explanation that makes perfect sense: the women in the Harvard study who took estrogen were more concerned about their health. That's why they took a hormone replacement in the first place.
In other words, estrogen didn't create healthy nurses, but health-conscious nurses did take estrogen. Meanwhile, the health-conscious nurses were less likely to develop heart disease . for any number of reasons.