Wednesday, November 24, 2003

Panel Calls For Testosterone Trials
By Mike Upchurch

A panel of experts, chaired by Duke’s Dr. Dan Blazer and including DCRI director Dr. Rob Califf, recommended last week that the government begin small-scale, preliminary studies of testosterone replacement in older men as soon as possible. Hormone replacement among aging men is becoming more and more common, despite very little hard evidence of its safety or effectiveness.

Dr. Dan Blazer

The committee, convened by the National Academy of Sciences’ Institute of Medicine (IOM), said that large-scale trials should be deferred until smaller studies can confirm testosterone replacement therapy’s safety.

But this decision was not unanimous. Some physicians felt this approach was too slow, especially considering the ever-growing number of prescriptions for testosterone being filled. The IOM report said that 1.75 million were written in 2002, more than double the number in 1999.

Dr. Richard Hodes, head of the National Institute on Aging, which will sponsor the proposed studies, acknowledged the urgency of the issue and vowed to accept the committee’s suggestion.

“We intend to move forward quickly,” said Hodes.

The issue is particularly in the spotlight after the revelations on hormone replacement therapy for women in recent years. After many years of combination estrogen/progestin treatment being thought to prevent heart disease, osteoporosis, and other ailments, a large government study revealed that any apparent benefits were small and outweighed by the increased risk of breast cancer and, surprisingly, heart disease.

Researchers hope to prevent a similar lag in testosterone research, but little is known about the effect of testosterone replacement in aging men. The IOM convened the expert panel for answers and recommendations on how to proceed.

“They felt like they were in a quandary and they were not certain what steps should be taken," said Blazer, who is a professor of psychiatry and behavior sciences at Duke.

Some evidence showed that testosterone helped alleviate symptoms of malaise, diminishing sex drive, muscle weakness, and other afflictions in young men who were not producing enough of the hormone. As men get older, testosterone levels gradually fall, and many doctors are prescribing testosterone to middle-aged and older men, seeking to stave off the supposedly associated problems. But some experts fear there is an increased risk of prostate cancer.

The committee found that very few studies have been done showing that testosterone replacement is safe or effective. On the other hand, they acknowledged that the existing research does not show that it is harmful, either.

“We were struck by the real paucity of studies and the relatively small number of subjects in them,” said Blazer.

The small studies to establish safety that were suggested by the committee are a first step that some experts feel is inadequate.

"Essentially what this means is we won't know for a long time," said Dr. Alvin Matsumoto of the Veterans Affairs Puget Sound Health Care System, who proposed larger studies.

Still others felt that even the small, pilot studies were premature and that more fundamental research needed to be done first.

“There is no consensus on what level of testosterone in an older man is too low,” said Dr. John McKinlay of the New England Research Institutes, “nor is there a consensus on how to measure testosterone levels, which can fluctuate from day to day.”

But Dr. Hodes and the majority of the committee felt the initial studies would give the medical community an advantage in concrete evidence that it did not have with hormone replacement therapy in women – an early start before treatment becomes pervasive.

With testosterone replacement, said Hodes, “the cow is not far out of the barn.”