Hormone Replacement Therapy (HRT)
May Still Pan Out

Hormone replacement therapy shouldn't be ruled out, despite the highly publicized shutdown of the Women's Health Initiative study in 2002, when health risks associated with the treatment were discovered.

So say the authors of a new review, published in the May 28, 2004 issue of Science. "The Women's Health Initiative [WHI] was good for what it was," said senior review author Judith L. Turgeon, a professor of internal medicine at the University of California, Davis, School of Medicine, who agreed the WHI was rightly halted when the health risks were discovered.

"But it used only one hormone formulation," she stressed. The trial studied a daily pill combination of 0.625 milligrams of estrogen and 2.5 milligrams of medroxyprogesterone. That formulation is very common in the United States.

But it's too early to forget about hormone replacement therapy altogether, said Turgeon, since a more precisely targeted form of therapy might prove safe for long-term use some day. That's because hormones affect many tissues in the body and affect them differently, she explained.

"All estrogens and progestins are not equal," Turgeon said. There are different forms produced by the body; the human ovary produces several types, including estrone and estradiol.

Hormones are not received the same way in different cells either, she said. And different methods of delivery, such as patch versus pill, can affect the body differently. In the WHI study, the women took the hormone combination in pill form, which meant it was processed through the liver, where some proteins that are connected to heart disease are then produced. A patch does not affect the liver.

"That is the core idea, that you can't indict all estrogen or hormone therapy on the basis of one [formulation studied]," Turgeon said. "By saying that we are going to eliminate all hormone therapy because the type of estrogen and progestin that they used in the WHI had adverse responses is not a good basis for rejecting all estrogen and progestins."

In the WHI, researchers found women on the combination pill had a slightly higher risk of heart attack, strokes and blood clots than women taking a placebo. The therapy was found to protect against bone fractures and colon cancer.

Turgeon takes issue with some factors that weren't well-publicized about the WHI study: The average age of the women was 63, and most had never had hormone therapy. Considering the average age of menopause is 51, the women were without hormones for 10 years or so, she said.

A high percentage of the subjects were also overweight or obese, and the more fat tissue, the more circulating estrogen a woman has. So that could have affected the trial's outcome, too, she added.

Custom-designed therapy might provide a better alternative, Turgeon said. "In the pharmaceutical business, they are capitalizing on the idea that you tweak a molecule just a little and the receptor [in the cell] is going to see it differently."

Eventually, she said, it might be possible for a woman to take a cocktail of different tweaked hormones to achieve a multitude of health effects, Turgeon said.

Another expert in the field praises the review. "I think it's outstanding; it's elegant and points up the major issue, that the sex hormones, both estrogen and progesterone, are tissue-specific in their actions," said Dr. Andrea Dunaif, the Charles F. Kettering Professor of Medicine at The Feinberg School of Medicine at Northwestern University.

"There are several type of hormone receptors," she said, "and there are different factors within each tissue in the body that determine how these hormones act."

In the future, she predicted, pharmaceutical companies will come up with more drugs known as selective estrogen receptor modulators (SERMS).

"SERMS are compounds that act as an estrogen in some tissue and block it in other tissues and have a neutral effect in others," Dunaif explained. Raloxifene (Evista) is used to increase bone density, for instance, without affecting other parts of the body.

For hormone-replacement purposes, Dunaif said, an ideal would be a SERM that blocks estrogen in the breast, for instance, and does not stimulate uterine growth, so risk of breast and uterine cancer would not increase. She predicted the next five years will bring such developments.

"For now, we have to be very cautious about all estrogen use until we have more data," Dunaif said. "We shouldn't be using any estrogen to prevent heart disease."

By Kathleen Doheny, HealthDay Reporter

More information

To learn more about hormone replacement therapy, visit the National Institutes of Health and the National Cancer Institute.

SOURCES: Judith L. Turgeon, Ph.D., professor, internal medicine, University of California, Davis School of Medicine; Andrea Dunaif, M.D., Charles F. Kettering Professor of Medicine and chief, Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago; May 28, 2004, Science

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