A Small Step for Womankind?

When it comes to hormone replacement, the bad news is good news.

Conservative columnist Charles Krauthammer makes a living being contrarian. Still, there's a definite (if ill- defined) boundary between contrarian-ism for profit and sheer fatheadedness, and in his July 15 Seattle Times column, Krauthammer swerved dangerously over the center line.

The subject of Krauthammer's column was the abrupt termination of the Women's Health Initiative (WHI) trial study of the risks and benefits of hormone replacement therapy (HRT) for menopausal women. The double-blind trial involving 16,000 women, some taking a combination of estrogen and progestin, the rest a placebo, showed a small but distinct risk of invasive breast cancer for women taking the hormone treatment.

From this Krauthammer concludes that whatever scientists tell you today, they'll tell you the opposite tomorrow, and points out that in Sleeper, when Woody Allen awakens in 2173, Science has discovered that cigarettes and hot fudge are good for you.

Aside from the insensitivity of comparing real-world life-and-death risk to a cinematic joke, Krauthammer's column—and much of the straight news coverage—entirely fails to grasp the real significance of the study's termination. This was not a case of science contradicting itself, but of genuine knowledge replacing a rickety consensus borne of isolated observations, ill-judged extrapolation, and lust for profit.

"Before this study was undertaken, there had been several observational studies suggesting that hormone replacement was beneficial in preventing calcium loss in older women," says UW epidemiologist Shirley Beresford, who was intimately involved in the selection of the participants in the WHI trial in this area. But observational studies aren't the same thing as a trial.

By the time the trial began, prescription of replacement hormones had extended far beyond prevention of osteoporosis; many, if not most, women taking the prescription drug Prempro were doing so because it often relieves the physical discomforts attendant upon menopause, not because of its putative long-term benefits. They were encouraged to continue taking it by vigorous advertising and promotion by the drug's maker, Wyeth Pharmaceuticals.

It was precisely to ascertain the wisdom of such widespread use that the WHI trial was undertaken. Other "observational" studies suggested that the combined progestin-estrogen formula in Prempro might reduce slightly women's risk of heart disease, and that it seemed to have no impact one way or the other on incidence of cancer of the uterus but might raise the risk of breast cancer. Beginning nearly eight years ago, scientists at 40 medical centers across the country began recruiting women willing to take part in an experiment to turn observations into facts.

In a way the trial was not classically double-blind but triple-blind, because clinical information about participants' health history was handled by a completely separate agency, the Data Safety and Monitoring Board. The function of this body was to collect all disease and mortality data about trial participants and turn it into something called the Global Risk Index (GRI). Only if that index hit a preset "redline" showing that study participants were suffering significantly greater ill health than their "control" companions would the black box containing the bulk data be opened.

The GRI redlined early this spring, after women in the study had been taking hormone replacement drugs an average of five and a half years. When their specific health histories were compared, the result was clear: Among 10,000 women taking the drug for just one year, eight more would be expected to develop invasive breast cancer than those receiving a placebo, with seven more suffering a heart attack, eight more a stroke, and 18 incidences of blood clots. On the positive side, the trial indicated six fewer colorectal cancers among those receiving the drug as well as five fewer hip fractures.

Does this mean the study was a failure? On the contrary, it was such a success that it could be concluded three years early. Instead of vague hopes and fears, women and their physicians now know what risks as well as benefits they face from hormone replacement and can make informed choices based on their own desires and clinical needs, not hearsay, infomercial, and clinical fashion. Krauthammer to the contrary, this is science at its best.

People who are no longer satisfied with having their health advice predigested by the media can consult several Web resources maintained by bodies governmental and private with no commercial or ideological ax to grind. The reports of the Women's Health Initiative on HRT and its other continuing programs can be accessed at www.whi.org. The Web site of the U.S. Preventative Services Task Force (www.ahcpr.gov/clinic/uspstfix.htm) offers the most up-to-date consensus judgments on treatment in controversial fields such as breast and colorectal cancer and depression.


Roger Downey's science column appears every other week.

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