Postmenopausal hormones up cancer risk

As a cub reporter in the mid-1970s, I did a brief stint writing for the newspaper in Oak Ridge, Tenn. And it was there I first learned about hormone replacement therapy. My editor had assigned me to talk to local women who sought to minimize the unpleasantness associated with menopause by periodically jetting over to Atlanta for estrogen-replacement treatments.

It was a novel therapy that East Tennessee’s medical establishment wouldn’t countenance (and which might even have been illegal at the time . . . I just can’t remember). In any case, I’ve always been surprised that throughout the intervening decades, research had failed to conclusively resolve whether such hormone therapy poses undue risks.

A report in the July 15 Journal of the American Medical Association now weighs in fairly conclusively on one aspect of the risk equation. It finds that “Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.”

That risk was not huge. The new data suggest such hormone supplementation might trigger about one extra ovarian cancer per 8,300 individuals treated. Among Danish women taking the supplements between 1995 and 2005, “hormone use is estimated to have resulted in about 140 additional cases of ovarian cancer,” report Lina Steinrud Mørch of the University of Copenhagen’s Rigshospitalet and her Danish colleagues.

But the new data focus only on ovarian malignancies. In fact, many women fill prescriptions for hormones to garner benefits that go well beyond providing mere comfort. For instance, a dozen years ago, we reported on a New England Journal of Medicine study following 121,700 nurses. Among those who had been at highest risk of heart disease, the treatment reduced their incidence of premature death from cardiovascular disease by 50 percent. That was five times the reduction calculated among estrogen users without heart risks.

The author of a second study described in that Science News report, Kevin Maki of the then Chicago Center for Clinical Research, noted that hormone-replacement therapy can work like a cholesterol-lowering drug in bringing elevated blood lipids under control. Indeed, I quoted him as saying:  “There is a sizable number of women for whom estrogen replacement alone may be sufficient to bring cholesterol levels down to their treatment goal.”

One caveat: The longevity benefit attributable to the therapy appears to fall within a decade — and disappears within five years of stopping the therapy.

Bones can also benefit from peri- and postmenopausal hormone supplementation. “Even a tiny dose of estrogen can boost bone density in elderly women significantly better than no dose at all,” my colleague Nathan Seppa reported in a 2003 story. However, the bone-sparing dose is well below the amount needed to arrest the menopausal symptoms that prompt most women to consider hormone therapy in the first place. (And, I have to wonder, wouldn’t lots of calcium, vitamin D, and weight-bearing exercise accomplish the same bone protection?)

A bigger concern are several potentially lethal side effects to hormone therapy. One study of the supplements’ safety was stopped short after participants seemed to face an increased risk of stroke, Seppa noted in a 2006 story. And hormone therapy appears to elevate risk of breast cancer. However, that risk emerges only after seven to 10 years of this therapy, Seppa reported.

But back to the new paper. Epidemiologists surveyed data covering an eight year period for all Danish women 50 to 79 years old and then tallied incidence of cancer on the basis of whether and what type of hormone therapy each had been taking. The Danes can do this because they have these fabulous health registries that provide copious — and anonymous — data on the entire population. After excluding women who had already experienced hormone-sensitive cancers, the researchers turned up 3,068 new ovarian malignancies.

The incidence of this cancer was highest among women who were taking hormone supplements, somewhat lower among those who had taken those supplements but had recently stopped, and lowest among never users or women who had stopped taking the supplements at least two years earlier. Supplement use elevated ovarian-cancer risk whether women had been prescribed estrogen alone or as part of a combo that included progestins. Whether a woman’s hormones were taken orally, by a drug-laced skin patch or from a vaginal ring also didn’t affect cancer risk much.

Among the Danish women studied, only 37 percent were taking supplemental hormones. And the slight excess in ovarian cancer incidence within this group suggests that only about five percent of the cancers observed during the study may be linked to hormone-replacement therapy.

Although this share may seem low, Mørch and her colleagues note, “ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use hormone therapy.” Indeed, fewer than four in 10 American women with this disease now survives 10 years.