WASHINGTON (Reuters Health) - Federal advisers began the first of several meetings Thursday that will result in recommendations later this year on how clinical trials can best assess the pros and cons of testosterone replacement therapy in aging men.

An unknown but significant number of older men have begun using patches, gels or other forms of testosterone in the hopes of reversing the aging process and a flagging sex drive, but there is no scientific evidence that hormone supplements can help. And there may even be some dangerous side effects, including an increased risk of prostate cancer.

"The chasms of our ignorance here are vast," Marc Blackman, an endocrinologist with the National Institutes of Health, told a 17-member Institute of Medicine advisory committee.

The panel has been asked to make recommendations regarding the pros and cons of testosterone replacement and its mechanism of action. They are also weighing how to properly inform potential study participants when the benefits and the risks of therapy are very unclear.

Over the last few decades, studies on non-elderly men with testosterone deficiencies have shown that replacement can counter increased body fat and cholesterol levels, decreased skeletal strength and decline in immune function associated with lower testosterone levels, said Blackman.

Four-to-five million non-elderly American men have below-normal testosterone levels, and 5% are receiving replacement therapy, he said.

The few studies in older men with naturally declining testosterone levels have shown that replacement therapy decreases fat and increases lean muscle mass. But only one, a small 15-person study in very frail elderly men, has shown any improvement in muscle strength or function. So it is unclear if increased muscle mass leads to better physical functioning, Blackman said.

It's also not known if testosterone replacement reduces the risk of disability, falls, or fractures, or otherwise improves health outcomes. And it's unclear if supplementation would have similar effects in healthy older men and physically impaired older men.

A big concern is whether testosterone supplementation will increase the risk of prostate cancer.

Scientists at Baylor College of Medicine have drawn up plans to carry out a large, long-term study of testosterone replacement therapy in older men. The trial has been put on hold while the IOM panel considers its merits.

Lead investigator Glenn Cunningham said the study aims to enroll 6,000 men over age 65. They would be in the study for four years, and then followed for five years more. The main goal is to see if testosterone replacement reduces fractures due to osteoporosis.

The researchers will also measure the effect on MIs and strokes, as well as mood, energy levels, cognition and sexual function.

Finally, they will assess whether replacement therapy increases the incidence of prostate cancer or leads to more procedures to reduce prostate size.

IOM committee member Paul Lombardo of the University of Virginia asked why any man would participate in the study, given the potential risks and sketchy benefits, and the easy availability of the drug outside of study.

"That's a good question," said Cunningham, who added that he thought men would take part to get osteoporosis treatment and prostate screening and to contribute to medical science.

National Institute on Aging chief Richard Hodes noted that women who took part in the Women's Health Initiative study of estrogen and progestin replacement therapy had to make the same kinds of calculations and most decided to participate.

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