Advice on hormone replacement therapy continues to evolve
By Shari Roan, Los Angeles Times

Hormone therapy has been one of the most confusing issues in women's health over the last decade. Now, a study from the Women's Health Initiative shows the increased risk of stroke found among women who take estrogen-only hormone therapy disappears after they stop the pills but the reduced risk of breast cancer -- believed by some to result from hormone use after natural menopause -- is maintained.

The findings should help women who have had a hysterectomy better weigh their risks and benefits of taking estrogen based on their age and symptoms. Here's the study in the Journal of the American Medical Assn. and the Los AngelesTimes article: "Estrogen-only therapy less risky than first thought."

Experts in women's health and menopause made a number of additional points regarding the new paper. Among them:

-- The new study, which follows women four years after they have stopped therapy, is unusual. Typically, studies examine participants while they undergo treatment with, perhaps, a brief follow-up period.

"It's important to follow women in clinical trials some time after we stop; that goes for benefits and risks. And that hardly ever happens in studies," said Andrea LaCroix, the lead author of Tuesday's paper and an epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle.

Knowing how long a risk or benefit lasts may help doctors figure out how long a medication should be prescribed, said Dr. Graham Colditz, a co-author of an editorial accompanying the JAMA study and an epidemiologist at Washington University School of Medicine in St. Louis.

"Is the risk still there for a day or a year or two years or five years? That is what is being asked here," Colditz said. "This is an additional, important aspect of this study. Seeing the risk [of stroke] go away after cessation of the trial is definitely helpful."

-- Critics of the Women's Health Initiative have long pointed out that the majority of women in the trial were well past menopause -- in their 60s or 70s. Most women take hormones for menopausal symptoms in their early to mid-50s. Tuesday's study confirms that the risks and benefits of estrogen therapy differ between younger and older women.

"We've had a study here where the vast majority of the data has no relevance to how the hormones are used in the real world," Colditz said. "When the results differed from expectation, people started to think, well, if we had all the women in the trial much closer to menopause we might have had a different answer."

-- The findings apply to estrogen only, experts stressed. In fact, a study published last year that followed women who took estrogen and progestin showed those who took hormones had an increased risk of breast cancer during the intervention phase of the study and that the risk remained higher afterward, as did the risk of dying from the disease.

"Closer to menopause is better for taking estrogen alone. But age didn't seem to matter for estrogen plus progestin for cancer risk," said Dr. Rowan T. Chlebowski, a medical oncologist at the Los Angeles Biomedical Research Institute and a co-author of the study. "There was a tendency to say it's all good. Estrogen alone may be good, but this new study doesn't say anything about estrogen and progestin."

Future studies may clarify the risks and benefits of estrogen plus progestin, he said. For example, women who take a combination of estrogen and micronized progesterone (a natural progesterone) may have a lower breast-cancer risk. But that remains unproven.

-- Researchers say the new study doesn't mean that women who don't have a uterus can take estrogen at menopause and continue for the rest of their lives. The study only looks at the risk and benefits after six years of use and about four years of follow-up after the therapy ended.

"Starting to take it in your 50s and then taking if forever -- that is not what this data show," LaCroix said.

-- The study showed that women who took hormones in their 50s had a lower risk of heart attacks and adverse events from chronic disease. That suggests that estrogen may confer some preventive benefits after all. But it's not proof, LaCroix said.

"What will be debated, and legitimately debated, is whether or not any of those reduced risks have prevention implications," she said. "We're not calling for that in the paper. There needs to be better understanding of why the differences in heart disease are there, why there is a lower incidence of breast cancer. Why a medicine can help some women and hurt them later needs to be better understood."

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