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Estrogen Mimic May Prove Safer Bone Builder

Molecule avoids downsides of hormone therapy

THURSDAY, Oct. 24, 2002 (HealthDayNews) -- A synthetic version of estrogen may provide all of the bone-preserving benefits of the hormone without any harmful effects on the reproductive system, new research has found.

Treatment with the substance, called estren, increased bone density and bone strength in female mice deprived of estrogen by removal of their ovaries. It was also effective in male rodents lacking testosterone.

Better yet, the compound seems to be invisible to cells in the uterus and breast, where estrogen is known to trigger cancers.

The value of hormone replacement therapy (HRT), often prescribed to combat osteoporosis, has been called into question over recent discoveries that its benefits may outweigh its risks.

Estren isn't a hormone, but its molecular structure is close enough to estrogen's that it fits cellular receptors specific to the sex steroid, says study leader Dr. Stavros Manolagas, director of the Center for Osteoporosis and Metabolic Bone Diseases in Little Rock, Ark.

Manolagas and his colleagues report their findings in tomorrow's issue of Science.

More than 8 million American women suffer from osteoporosis, putting them at significant risk of painful and debilitating fractures. The bone-thinning disease also occurs in about 2 million men, and another 18 million or so people have weakened skeletons that predispose them to osteoporosis.

HRT has been in scientific limbo lately. Researchers last May halted a major government-funded trial of one form of hormone supplements, estrogen and progestin, after determining that its benefits, which included fewer fractures, didn't outweigh the risk of rare but serious side effects, including heart trouble and breast cancers. Another arm of the trial looking at estrogen therapy alone is continuing.

In the latest study, Manolagas' group imbedded slow-release pellets of estren under the skin of female and male mice, then measured several qualities of the animals' bones over time. To simulate the effects of menopause, during which estrogen levels plummet, some of the female rodents had their ovaries removed.

The pellets led to bone formation and strength that was at least as impressive as that of rodents with normal estrogen levels, the researchers say. This effect on the skeleton was identical to that of treatments with a version of testosterone -- another bone-forming hormone -- in male mice missing their testicles.

Estren spurred the formation of bone-building cells called osteoblasts, which estrogen typically does not do, and led to substantially wider bones than in mice given estrogen. The ability of bones in the estren-treated mice to withstand compression was greater than that of the female animals receiving estrogen, and similar to that of male mice that got testosterone.

Estren's transparency to reproductive cells skirts the breast cancer problem, Manolagas says. Whether it might interfere with heart health "is the $6 billion question," he says, adding the researchers have not fully explored the toxicity of the molecule.

Estren, which is still experimental, wouldn't be the only drug designed to mimic the best of estrogen while minimizing its potential side effects. A family of drugs called selective estrogen receptor modulators (SERMs), such as raloxifene, is currently being used to thwart osteoporosis.

Dr. Eric Orwoll, a bone specialist and director of the General Clinical Research Center at Oregon Health Sciences University in Portland, calls the new study "promising in two ways."

First, it helps flesh out the mechanics of sex hormones. And, it provides hope for a new addition to the treatments for osteoporosis, Orwoll says.

However, he adds that it's not entirely clear that estren's effects are so distinct from those of estrogen or SERMs. "What we don't understand is exactly how sex steroids do work in bone. Maybe sex steroids utilize this mechanism as well," he says.

Despite HRT's current tribulations, Manolagas says women will need the treatment.

"Estrogen replacement affects half the population of the earth for over 40 percent of their life," he says. "Women are going to be living 40 percent of their life without the hormones that made them women. Until 100 years ago, life expectancy and menopause were coinciding."

What To Do

For more on osteoporosis, try the National Osteoporosis Foundation or the National Institutes of Health.

SOURCES: Stavros Manolagas, M.D., Ph.D., Central Arkansas Veterans Health Care System, University of Arkansas for Medical Sciences, and director, Center for Osteoporosis and Metabolic Bone Diseases, Little Rock; Eric Orwoll, M.D., director, General Clinical Research Center, Oregon Health Sciences University, Portland; Oct. 25, 2002, Science
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