A group of 41 men who received testosterone replacement therapy for 6 months saw no increased risk of prostate cancer, according to a new study in the Journal of the American Medical Association. But with such a small group followed for such a short time, experts say, it’s too soon to say for sure just how safe testosterone replacement might be.
Why it’s important: Testosterone replacement therapy is increasingly common in the United States, say study author Leonard S. Marks, MD, and colleagues. Doctors wrote 1.8 million prescriptions for it in 2002; by 2005, that number had grown to 2.3 million, according to background information in the study. The treatment is often used to address symptoms of "male menopause" — the sexual problems, depression, and muscle and bone loss that can occur as men’s testosterone levels decline with age.
But testosterone can also make prostate cancer grow faster, so it’s not known how safe it is for men to take this hormone. A study involving thousands of men is needed to answer that question, some experts contend. Before taking that step, however, an expert panel from the Institute of Medicine recommended doing smaller safety and effectiveness studies like this one.
What’s already known: Men who have advanced prostate cancer should never take testosterone, explained Marks, medical director of the Urological Sciences Research Foundation and clinical professor in the surgery/urology department at the University of California, Los Angeles, School of Medicine. Giving testosterone to men in this situation can lead to an increase in cancer-related symptoms such as bone pain, urinary obstruction, nausea, and vomiting, studies have shown, and can even lead to death. It’s not known, however, how testosterone replacement would affect a healthy prostate. Some studies have cited cases where men taking the hormone have gone on to develop prostate cancer. But others have shown no bad effect of testosterone on prostate size or levels of PSA (prostate-specific antigen), which can both be markers of prostate cancer.
How this study was done: Marks and his colleagues recruited men between the ages of 44 and 78 who did not have prostate cancer but who did complain of symptoms related to low testosterone. The men were given a prostate biopsy at the beginning of the study, where cells were taken from their prostate gland and examined under a microscope. The men were then randomly placed into 2 groups: one group got injections of testosterone for 6 months, while the other got shots of an inactive placebo substance. No one knew which group he was in. At the end of the study, another prostate biopsy was taken and compared to the first sample. The researchers looked at testosterone levels in the men’s blood and in the prostate gland itself, changes in prostate cell growth or death, and changes in genes that are known to be affected by testosterone.
What was found: Forty of the 41 men completed the study. Those who got testosterone injections had higher levels of the hormone in their blood, but not in their prostate glands. Researchers found no evidence of abnormal cell changes in the prostate gland, and no evidence of gene changes.
Prostate cancer was found in 6 men: 4 who were getting the placebo and 2 who were getting testosterone.
"Clearly, testosterone was not stimulating the development of new cancers," Marks said during a news conference about his findings. "Very likely these 6 cancers were there from the beginning."
The study was not designed to see if hormone therapy would improve the symptoms of low testosterone the men were experiencing; therefore, the researchers did not report on that issue.
The bottom line: Short-term testosterone therapy appears safe for the prostate, but many questions about the treatment remain unanswered, says Marks. For instance, many men have early-stage prostate cancer that can’t be detected with PSA tests or physical exams. This study can’t tell whether testosterone therapy would have a negative effect on those men.
It was also a very small and very brief study, cautioned Durado Brooks, MD, director of prostate and colorectal cancers at the American Cancer Society. Many men take testosterone therapy for years, he explained. The hormone’s effects might be quite different over a period of years rather than months, and longer, larger studies are the only way to find out.
Marks agreed more research is needed before men rush to get testosterone prescriptions. And before their doctors comply.
"There is a concern that some physicians may misinterpret these data and start using testosterone willy-nilly, and my hope is that it won’t be used in this way," he said. "There are some limitations in how much you can generalize from this project."
