A multi-disciplinary task force, led by the Institute of Medicine (IOM) and supported by the National Institute on Aging (NIA), will evaluate the pros and cons of conducting clinical trials of testosterone replacement therapy in older men. The year-long task force, announced today by the NIA and IOM, will make recommendations regarding the design, safety, and ethics of clinical trials of this intervention, including whether such studies are even warranted.
The task force was conceived, in part, because of growing concerns about an increase in the number of older men apparently using testosterone replacement therapy (TRT) in the absence of adequate scientific information about its risks and benefits, said NIA Director Richard Hodes, M.D.
"In forming this partnership with the IOM, the NIA is moving forward in two directions: One, to determine the extent and nature of the risks and benefits, and two, to explore the scientific and ethical questions that must be asked before any clinical trials of this intervention can be safely and prudently conducted," Dr. Hodes said.
The task force, which will consist of prominent scientists specializing in epidemiology, endocrinology, urology, oncology and other relevant fields, will review and assess the current state of knowledge concerning testosterone replacement therapy (TRT) and prepare an evidence-based report outlining the benefits and adverse effects of this intervention, the potential public health impact of TRT in the United States, and the ethical issues involved in the conduct of a clinical trial of TRT. The committee will conduct four meetings and one workshop in the next 12 months.
"Although some older men who have tried these supplements report feeling `more energetic' or `younger,' testosterone supplementation remains a scientifically unproven method for preventing or relieving any physical and psychological changes that men with normal testosterone levels may experience, as they get older. Until more scientifically rigorous studies are conducted, the question of whether the benefits of testosterone replacement outweigh any of its potential negative effects will remain unanswered. This task force will help us address the huge challenge we face in designing clinical trials that safely and ethically explore this question," said Stanley Slater, M.D., deputy director of the NIA's Geriatrics and Clinical Gerontology Program.
Testosterone is a vital sex hormone that plays an important role in puberty. But contrary to what some people believe, testosterone isn't exclusively a male hormone, Dr. Slater said. Women produce small amounts of it in their bodies as well. In men, testosterone is produced in the testes, the reproductive glands that also produce sperm.
As men age, their testes often produce somewhat less testosterone than they did during adolescence and early adulthood, when production of this hormone peaks. But it is important to keep in mind that the range of normal laboratory values for testosterone production is vast. So while there are some declines in testosterone production with age, most older men stay well within normal limits, and the likelihood that a man will ever experience a major shut down of hormone production similar to a woman's menopause, is remote, according to Dr. Slater.
In fact, many of the changes that take place in older men often are incorrectly blamed on decreasing testosterone levels. Some men who have erectile difficulty (impotence), for instance, may be tempted to blame this problem on lowered testosterone. However, in the vast majority of cases, erectile difficulties are due to circulatory problems, not low testosterone.
Still, a small percentage of men may be helped by prescription testosterone supplements. These supplements often are prescribed to men whose bodies do not make enough of the hormone—for example, men whose pituitary glands have been destroyed by infections or tumors, or whose testes have been damaged. For these few men who have extreme testosterone deficiencies, supplements in the form of patches, injections, or topical gel may offer substantial benefit. Supplements may help a man with low testosterone levels maintain strong muscles and bones, and increase sex drive. However, what effects testosterone replacement may have in healthy older men without these extreme deficiencies will require more scrutiny, Dr. Slater said.
Many other questions remain about the use of this hormone in late life. It is unclear, for example, whether men who are at the lower end of the normal range of testosterone production would benefit from supplementation. Some investigators are also concerned about the long-term harmful effects that supplemental testosterone might have on the aging body. It is not yet known, for instance, if testosterone supplements increase the risk of prostate cancer, the second leading cause of cancer death among men. In addition, studies suggest that supplementation might trigger excessive red blood cell production in some men. This side effect can thicken blood and increase a man's risk of stroke.
"The NIA is investigating the role of testosterone supplementation in delaying or preventing frailty," Dr. Slater said. "Results from preliminary studies involving small groups of men have been inconclusive, and it remains unclear if supplementation of this hormone can sharpen memory or help men maintain strong muscles, sturdy bones, and robust sexual function."
The NIA, a component of the National Institutes of Health, leads the federal effort in supporting and conducting basic and clinical research on aging and the special needs of older people. For information about the NIA, visit the website at http://www.nia.nih.gov/ .