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I hesitate to tackle this one, but it's a good example of a larger issue: Are medical studies asking the right questions?

Estrogen replacement therapy was first available in 1942. By now its effects should be obvious, yet it continues to be controversial. Is the problem a lack of sufficient information, or is there something inherently unresolvable at the heart of the estrogen story?

Ask Dr. Bob Dr. Robert Burton, who is a neurologist and novelist, answers health questions every Monday in Salon Health & Body. Please e-mail your queries to him at AskDrBob@ salon.com.

I've done my reading and talked to the experts, yet remain confused and uncertain. My politically incorrect, shoot-from-the-hip conclusion is that more studies aren't going to solve the problem. The controversy is here to stay because the problem is in the nature of medical studies in general. Questions for which there are few confounding factors and absolute, objective measures are relatively simple to answer. But once there are multiple interacting variables or the effects being measured are not entirely objective, all bets are off.

Let's take a look at HRT and see what is and isn't possible to understand. Estrogen helps prevent osteoporosis. We know this because we have a specific measure of bone density and can compare post-menopausal women who take and don't take HRT. We can argue about measurements of bone density, but these are minor quibbles that can be resolved.

Similarly, we know that estrogen reduces the incidence of cardiovascular disease. Using objective tools such as EKGs, cardiac enzymes and MRI scans, we can objectively determine the incidence of heart attacks and strokes.

But what about HRT and breast cancer? Breast tissue contains estrogen receptors; estrogen stimulates cell growth. Most breast-cancer cells (perhaps two-thirds) are estrogen-receptor positive (respond to estrogen). There is a statistically increased incidence of breast cancer in patients on HRT. Tamoxifen, which blocks the effects of estrogen on breast tissue, is a major advance in chemoprevention of breast cancer, though not without significant side effects, including an increased incidence of endometrial cancer.

So isn't estrogen bad for women at risk of, or who've had, breast cancer? It's not that simple. High-dose estrogen (stilbestrol) was once a treatment for metastatic breast cancer, with large tumors undergoing dramatic, though temporary, reduction when exposed to estrogen. Several recent studies have shown that women taking HRT when their breast cancer was diagnosed had a better prognosis than those not on HRT. (Many doctors in the U.K. now feel that HRT is to be recommended for patients with a history of breast cancer.)

My first impulse is to wonder if some studies are better than others, or whether some overarching study might be able to answer the question. But I stop myself. The problem may lie elsewhere, in hidden possibilities and the unpredictability of interacting influences.

Though we are great at planning and calculating, we all recognize the profound role of random or inconsequential events -- the missed planes, serendipitous meetings and odd mistakes -- in shaping our lives. Such events, though we try to control them, also shape the outcome of medical studies.

A weather forecaster understands this dilemma, shrugging when we ask if it's going to rain tomorrow. "Maybe. I'd say an 80 percent chance." Because we can cover our bases by carrying an umbrella and a sun hat, we do not fret over the limitations of the weather report. Not so with medical studies. Too much is at stake and we need to feel in control of our health, so we act as though medical problems have more definite solutions than weather predictions.

(If you think that, with a proper design, all medical questions can be answered, consider the field of nutrition. Every week there's a new study with different recommendations. I confess that it's beyond me how to determine what is the optimal combination of vitamins, minerals, herbal supplements and fat and fiber content. It would be like predicting world weather for the next millennium.)

Which leaves women with this impossible question: If you are at risk for breast cancer, would you prefer to have a statistically greater chance of developing the disease or possibly a better prognosis if you already have it? Are the two statements in any way comparable or is this apples versus bananas? And how would we know?

Next page | We need a new way of asking medical questions and we need a new way of reporting results