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Research Highlights
New Study Promises Safer Hormone Replacement Therapy
Taken from the Veterans Health Administration Highlights dated November 1, 2002
A VA scientist in Arkansas has identified a synthetic estrogen-like compound that reverses bone loss in mice without affecting the reproductive system, as does conventional hormone replacement therapy. The finding, reported in the Oct. 25 edition of Science, could lead to new therapies to prevent osteoporosis for millions of women and men, and enable safer alternatives to existing hormone treatments, shown earlier this year to pose more serious risks than previously thought.
"We are developing a new class of pharmaceutical agents with the potential for bone-building, sex-neutral hormone replacement therapy," said lead investigator Stavros C. Manolagas, M.D., Ph.D., an endocrinologist with the Central Arkansas Veterans Health Care System and the University of Arkansas for Medical Sciences.
Manolagas’ team reported last year in the journal Cell that sex hormones exert their bone-protecting and reproductive effects through separate cellular mechanisms. The researchers also identified a synthetic estrogen-like hormone—"estren"—to work in one pathway but not the other. The new study is the first time scientists have demonstrated in animals how synthetic hormones can build bone without affecting reproductive organs.
Manolagas and colleagues tested the effects of estren, compared to conventional estrogen and testosterone, in male and female mice. ome of the mice had their ovaries or testis removed, to halt the production of their natural sex hormones. The researchers then gave back a naturally occurring form of estrogen, for females, or testosterone, for males, to one group of sex-organ-deficient mice. Another group received the synthetic hormone estren, regardless of sex.
Remarkably, estren was even more effective than estrogen for females, and just as effective as testosterone for males, in helping bone. In fact, while estrogen only prevented bone loss, the estren actually increased bone density and strength, even to levels above those of the female mice with their ovaries intact.
Most important, the estren—unlike the estrogen or testosterone—had no effect on the weight of the uterus or seminal vesicle. Moreover, the estren, unlike estrogen, did not trigger the growth of breast-cancer cells in a Petri dish. While estrogen preserves the mass and function of female sex organs, it has also been shown to cause tumors with prolonged use as a therapy.
Manolagas said the results of the study show that synthetic hormones such as estren may provide a safe form of hormone replacement therapy that preserves and even builds bone, without affecting the reproductive system. He added that estren may even provide other anti-aging benefits, such as protecting blood vessels and nerve cells, since these tissues appear to respond to sex steroids through the same mechanism as does bone tissue—without involvement of the reproductive organs.
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