Finding out if hormone therapy is right for you

When results of the Women’s Health Initiative, that famous study that made us all throw away our hormones, were released, we physicians uttered a collective “Huh?”

We thought that hormone replacement therapy during menopause helped protect women from getting heart disease, because when we looked at large studies following women taking HRT, that was what they showed.

But the WHI was the gold standard kind of study – a placebo controlled, randomized, double-blind study (half the women took placebo pills, who took what was the luck of the draw and no one knew who was taking what) – and it said different. Not only did HRT with estrogen plus progesterone not protect against heart disease, it made things worse in the heart department, it increased the risks of stroke and blood clots and it increased the risk of breast cancer slightly (which we already knew). It helped the bones stay strong, but that benefit didn’t outweigh all those risks.

Up until that point, we had been looking at studies following women who were on HRT and comparing them to a similar group who weren’t. Those studies seemed to show that women on HRT had fewer heart attacks and strokes. But maybe the groups weren’t as similar as we thought. Maybe the women on HRT were healthier; maybe doctors were reluctant to start women with chronic diseases or family risk factors on hormones? That’s called selection bias.

But a lot of us had some strong reservations about the WHI. The average age of women in the study was 63 – hardly the time when most of us would be starting our hormones. And it only looked at one hormone preparation – Premarin with or without a synthetic progesterone. Would the results have been the same if another estrogen were used? There are certainly lots to choose from. What role did the progesterone play?

Now we have two substudies from the WHI looking at women who have had hysterectomies and were therefore taking Premarin alone. (The progesterone is added to prevent cancer of the lining of the uterus.) Close to 11,000 women made up this group. Half got Premarin, the other half got the look alike placebo pill. In the first study, the researchers looked at the end points of heart attacks and cardiac death. In the second, they looked at breast cancer.

And here’s what they found: Taking estrogen alone did not increase a woman’s chance of having a heart attack or a cardiac death. Nor did it increase her risk of breast cancer. These are not the results we heard from the initial WHI reports, which came out with a flurry of publicity when the study was stopped early because the risks of HRT outweighed the benefits.

Of even more interest is that in the group of women ages 50 to 59 – just the age that women might be taking estrogen to ward off the symptoms of menopause – there was a trend towards a protective effect against heart attacks and cardiac deaths. That’s what we thought our observational studies were telling us.

There are lots of possibilities here when we contemplate the “why” of these results. Perhaps the progesterone, not the estrogen, is the culprit. Perhaps starting hormones at age 50 affects a woman’s body differently than starting them at age 65. There is a study under way that is looking at the effects of HRT started in more appropriately aged women, but those results won’t be out until the end of the decade.

Meanwhile, it is not unreasonable for us to remain a bit skeptical about hormone replacement therapy as the next best thing since sliced bread. Nor is it unreasonable to use it for what we know it’s good for while the researchers sort this all out. We know that HRT is the most effective therapy for menopausal symptoms that can be truly debilitating for some women. This is a complicated topic, and each woman has her own unique history. For now, the best thing to do is to talk it over with your health-care provider.