U.S. scientists have found that a synthetic compound mimicking the female hormone estrogen helps build bone in laboratory mice, without affecting their reproductive organs. The finding offers hope that post-menopausal women might be able to take the treatment someday, without the cancer risks associated with estrogen replacement therapy.
Among the weakening effects of old age is osteoporosis, the loss of bone density that heightens the risk of debilitating fractures. Women after menopause are much more susceptible than men, because they stop producing the hormone estrogen, which helps maintain bone mass.
Estrogen replacement therapy prevents osteoporosis, but University of Arkansas physician Stavros Manolagas says it causes unwanted side effects. "When you combine estrogens with progesterone, then you do have a small increase in the risk of breast cancer, in the risk of heart attacks, and pulmonary embolism [blockage of the artery between the heart and lungs].
Another side effect is a modest rise in uterine cancer risk. Several months ago, a major clinical study on the long-term use of estrogen plus progesterone found that these risks outweighed the therapy's bone maintenance benefits.
Now, Dr. Manolagas and colleagues report in the journal Science that a synthetic compound called estren may solve this problem.
"From the studies we've done so far in the mouse, it looks as if estren has the beneficial effects of estrogen on the skeleton, without affecting the reproductive organs, like the breast and the uterus," he said.
Dr. Manolagas has found in previous studies that estrogen operates in two different ways in the body. In one way, it causes a series of chemical signals that regulate the activity of genes in the body's cells. This is the pathway that has been linked to cancer in reproductive tissues.
In the second mode of action, estrogen promotes bone growth, by extending the lives of bone-building cells and shortening the lives of cells that destroy bone.
The University of Arkansas mice studies found that the new compound, estren, acts only in this second way.
Estren renewed bone in female and male mice suffering osteoporosis, after the removal of their estrogen and testosterone producing organs, the ovaries and testes.
This is hopeful for older men, as well as women, despite their smaller risk for brittle bones. Estren might be able to replace treatments with male hormones, called androgens, because androgens are also linked to cancer.
"By virtue of the fact that this compound does not affect reproductive tissues, it can be given to men and to women," he said. "If you now give estrogen to a man, obviously, you are going to have feminizing side effects. Or if you give androgen to a man that has prostate cancer, and we need to eliminate any androgenic action, we have no treatment with hormone replacement. This new compound seems to be well suited for conditions like that."
If small preliminary studies in people show results like those in mice, Dr. Manolagas predicts that large scale human testing will occur in two to three years.