The Hormone Conundrum
An abrupt end to a major menopause study leaves women as confused as ever
Not surprisingly, estrogen use skyrocketed through the 1970s, until researchers documented that women taking estrogen had four or more times the risk of developing endometrial cancer compared with those who did not use the drug. Estrogen use plummeted until doctors began prescribing another hormone, progestin, to be taken in combination with estrogen. The idea was to mimic women's natural hormonal cycles and eliminate the endometrial cancer risk. By 1999, an estimated 15 million women had prescriptions for hormones.
The WHI study changed all that. Today, according to Wyeth, the company that makes the two bestselling hormone pills, about 8.5 million women use some type of hormone therapy. The vast majority take estrogen, not estrogen plus progestin, and nearly half use Wyeth's Premarin. Clearly, the results of the estrogen-only trial are exceedingly relevant.
The problem is that nobody knows what the results are yet. So stopping the estrogen study is causing a firestorm among researchers. The WHI's Data Safety and Monitoring Board, a group of outside experts in the safety of clinical trials, advised stopping the earlier trial because the data clearly showed the drugs were causing more harm than benefit to women. The safety "boundary" was crossed when a steep increase in invasive breast cancers became evident within five years. "For the estrogen and progestin trial, we basically laid out everything for the world," says Marcia Stefanick, professor of medicine at Stanford University, a lead WHI investigator. But she questions whether the same consensus existed for stopping the estrogen study last week.
The WHI's Alving concedes it did not. No safety boundary was crossed, she says, and indeed the board was divided over stopping the trial. Some members favored sending a letter to the participants describing the stroke risk and allowing the women to decide for themselves whether to continue. That's the route Sharon Lubbers, 60, of Portland, Ore., would have preferred: "Here you are, participating with a long-term commitment. You've invested seven years. I think it would have been better if we had been notified of the results and given the option to continue." She joined the study because she wants her two daughters and six granddaughters to have more information than she had, and she's disappointed it has ended early. "Are they really going to get all the answers they need?" she wonders.
Alving and other officials say yes and that another year of follow-up would not have changed their conclusions. "If you're driving a car and you come to a cliff, do you keep driving and go over the edge?" Alving asks. "This trial was clearly headed to a boundary."
Jacques Rossouw, WHI's project officer, believes strokes were the critical issue. "Stroke is extremely serious. This was a trial to show benefit, and benefit was predicated on a reduction in heart attack. If there is none, and with an increased risk of stroke, then it's important." Though no firm statistics are yet available on the number or the severity of unexpected strokes, WHI officials say there were about as many as in the earlier trial--or eight extra strokes per 10,000 women. That translates to about 6,800 excess strokes per year.
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