Study Links High Testosterone and Prostate Cancer Risk
Researchers last week cautioned older men on the use of testosterone replacement therapy (TRT) after reporting the results of a study in which high levels of testosterone in men over age 50 were associated with a significantly increased risk of prostate cancer. Researchers from Johns Hopkins University and the National Institute on Aging (NIA) presented the data at the American Urological Association annual meeting.
The study analyzed nearly 2,900 serum samples collected over a 40-year period from 794 men participating in the Baltimore Longitudinal Study on Aging. Men with the highest free testosterone index had an 88 percent increased relative risk of prostate cancer compared with men with the lowest levels, says the study's lead author, Dr. J. Kellogg Parsons.
Dr. Howard L. Parnes, chief of the Prostate and Urologic Cancer Research Group in the National Cancer Institute's (NCI's) Division of Cancer Prevention, agrees that the questions about prostate cancer risk and TRT are legitimate. "The concern is not limited to men at particularly high risk for prostate cancer," he says. "That's not just based on the results of this study, but on what we know of the biology of prostate cancer in general. These data are consistent with those concerns.
Testosterone has been shown to promote tumor growth in men with metastatic prostate cancer, while research dating back to the 1940s has linked severe dips in testosterone to reduced tumor size in the same patient group. By increasing testosterone levels through TRT, clinicians feared that men with inactive prostate cancer cells could be significantly increasing their risk for developing prostate cancer - a fear that these new data appear to buttress.
The U.S. Food and Drug Administration has approved several testosterone therapy products to treat hypogonadism, a state of extremely low testosterone levels that can cause symptoms such as loss of bone density and muscle mass and erectile dysfunction. There is some uncertainty, however, about what represents true hypogonadism and how many men really require TRT. Despite this uncertainty, there were more than 1.75 million prescriptions for testosterone therapy products in 2002, an increase of 170 percent from 1999. More than 85 percent of these prescriptions were for men under 65, according to IMS Health.
"That is a worrisome trend," says Dr. Parnes. "Aside from men who have true hypogonadism, there are little data to support the use of testosterone for symptoms that are often assumed to be related to decreasing levels of testosterone that naturally occur with aging," he says.
There are proponents of using TRT in men who aren't experiencing extreme symptoms associated with hypogonadism, provided that they are closely monitored. In addition, Dr. Parsons' conclusions about TRT, drawn from the prospective data he presented last week, contrast with the results of a review of TRT studies published in the New England Journal of Medicine in January. No causal relationship between testosterone replacement and prostate cancer was found.
Nevertheless, there appears to be agreement that more research is needed. Because of the uncertainty surrounding TRT and its growing use, in 2002, NCI and NIA asked the Institute of Medicine (IOM) to analyze the available research on TRT and provide recommendations on whether and how to proceed with research into its use in men aged 65 and older.
In a report released last November, the IOM's expert committee on this issue concluded that, because of uncertainty about many issues surrounding testosterone and its effects on men's health, small studies that prove TRT is effective are needed before any large-scale trials addressing safety are launched. According to an NIA spokesperson, the institute is continuing to evaluate the IOM report, and early-phase clinical trials are planned.