USC Health Now

Hormone replacement therapy is on the outs for women, except maybe to help menopause symptoms for a short time. Does this mean all hormone therapies are bad? New research suggests some therapies may help.

by Orli Belman and Athan Bezaitis

Before the findings from the Women’s Health Initiative studies about hormone replacement therapy came out early in the decade, hormone replacement was considered a general fountain of youth for women who wanted to avoid many of the bad effects of aging and menopause: hot flashes, Alzheimer’s, heart disease, even tooth loss.

But then the massive national studies were stopped early because they found several negatives: combination therapies (hormones estrogen and progestin together) increased a woman’s risk of breast cancer, and estrogen alone increased a woman’s risk of stroke.

Then this winter came even more dramatic evidence against HRT: a study found hormone therapy use in women dropped 68 percent between 2001 and 2003, and shortly thereafter breast cancer rates dropped by 10 percent to 11 percent. Because the drop in cancer rates was sustained in 2004, doctors who led the study said they felt it wasn’t a fluke – that the drop in breast cancer rates was directly correlated to the drop in HRT.

“Hormones, including estrogen-alone and estrogen plus progestin, should not be used for the prevention of chronic disease,” says National Heart Lung, Blood Institute Director and Women’s Health Initiative Director Elizabeth G. Nabel, M.D. “Current recommendations are that hormone therapy should only be used to treat menopausal symptoms and should be used at the smallest effective dose for the shortest possible time.”

Does this mean all hormone therapy will go the way of the dinosaur? Not necessarily, suggest some USC researchers.

For example, researchers at USC have discovered a direct link between the loss of testosterone and the development of an Alzheimer’s-like disease in mice. Testosterone treatment, they found, slows progression of the disease.

The study, published in the Dec. 20, 2006, issue of The Journal of Neuroscience, predicts that testosterone-based hormone therapy may be useful in the treatment and prevention of Alzheimer’s disease in aging men.

“We’ve known that low testosterone is a risk factor for Alzheimer’s disease, but now we know why,” says Christian Pike, senior author and associate professor at the USC Leonard Davis School of Gerontology. “The implication for humans is that testosterone therapy might one day be able to block the development of the disease.”

In order to investigate testosterone’s role in the development of Alzheimer’s disease, the team took away the ability of male mice to produce testosterone. Some mice then were given a form of testosterone while others were given none.

The mice with lowered testosterone showed increases in levels of the protein B-amyloid (AB), which has been widely implicated as playing a role in the development of Alzheimer’s disease. They also showed signs of behavioral impairment.

The mice that were given testosterone showed reduced accumulation of AB and less behavioral impairment.

“These results are exciting because they tell us that we are on to something that is worth pursuing,” Pike says. “The next step is to look at what the long-term effects of testosterone therapy are in aging men.”

This study adds valuable new information to understanding the role of hormones in aging and disease.

Evidence has also suggested that testosterone may be useful in other neurological conditions. In a recent presentation at the Society of Neuroscience’s annual meeting, Chien-Ping Ko, professor of biological sciences at USC College of Letters, Arts and Sciences, reported that testosterone therapy improved muscle coordination in mice suffering from a form of Amyotrophic Lateral Sclerosis, or Lou Gehrig’s Disease.

But don’t expect physicians to rush to prescribe hormones any time soon.

“It remains an active area for women’s research—it’s a very unsettled area, and the trials to date show differing outcomes,” says Howard N. Hodis, M.D., professor of medicine and director of the Atherosclerosis Research Unit in the Keck School of Medicine.

In the meantime, women can still find benefits from taking hormones, including the relief of menopausal symptoms, preserving bone density and reducing risk of diabetes, even if their long-term benefits and risks are still being clarified.

“Are there risks? Yes, like any other medication, but they’re not great enough to create panic and make everyone using hormones get off them,” concludes Hodis.