Men with low testosterone die earlier; reasons unclear

Experts say more research is needed to answer the question of whether men should be prescribed the hormone.

By Victoria Stagg Elliott — Posted Sept. 11, 2006

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Older men with low testosterone levels are likely to die sooner than those who have normal amounts of this hormone, according to a study published last month in the Archives of Internal Medicine. But the authors and other experts say that rather than supporting the increasingly common practice of prescribing this hormone to men as they age, the findings highlight the continuing need to fill in the knowledge gaps.

"There's a lot of controversy over prescribing testosterone. So many more men are using it, and we don't really know the risks and benefits. We really need to do more research," said Molly Shores, MD, lead author and director of the Geriatric Psychiatry Clinic at the VA Puget Sound Health Care System in Seattle. "This [study] is another piece of the puzzle of trying to understand what role low testosterone plays in older men."

Researchers analyzed retrospectively the medical records of 852 men receiving care at the VA Puget Sound Health Care System from 1994 until 1999. Only about a fifth of those with normal testosterone died during this period. More than a third with low levels did.

Experts expressed caution at interpreting the data as supportive of testosterone supplementation. While this study found an association between low testosterone and death, it did not prove whether the hormone was the cause, whether the low levels indicated that other disease processes were to blame, or whether the presence of other hormones or unmeasured factors possibly led to the mortality.

"The most dramatic thing about this study is that these veterans are dying at a huge rate," said Stanley Korenman, MD, an endocrinologist and associate dean for ethics at the David Geffen School of Medicine at the University of California, Los Angeles. "But because of the way they gathered the data, they don't know why. We don't really know what's going on with these guys. I certainly think that low testosterone levels are a sign of something wrong. But this study does not answer the question: Does testosterone therapy do any good?"

For example, those who had low levels of testosterone tended to weigh more and had higher rates of diabetes. But again, causation was ambiguous. "What comes first is not clear," said Dr. John Morley, director of geriatrics and acting director of endocrinology at Saint Louis University School of Medicine.

Additionally, many experts also said generalizability to the general male population was limited, because those who receive care from the VA tend to be sicker and of lower socioeconomic status than those who receive care elsewhere.

"It's a uniquely different population," Dr. Morley said.

And although this study pointed out the need for more research, there are still many barriers to carrying it out.

Many complain that financial support for such research is slim and that lab tests for testosterone measures are not consistent from facility to facility. Specifically, standard definitions of what constitutes healthy testosterone levels at various stages in a man's life are not widely accepted.

"There are not good normals established," said Katherine Margo, MD, predoctoral director in the Dept. of Family Practice and Community Medicine at the University of Pennsylvania in Philadelphia.

Because the hormone increasingly is being prescribed, the unanswered questions are becoming more and more important.

"Testosterone treatment may be reasonable, but we're still missing that major study," Dr. Morley said. "We need interventional studies to show that treating people makes a difference. It's so overdue that it's frightening that we have not done it."

The Institute of Medicine 2003 report, "Testosterone and Aging: Clinical Research Directions," suggested that many more small studies were needed to assess fully the benefits of taking testosterone before a large-scale randomized trial, along the lines of the Women's Health Initiative, could be considered.

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External links

"Low Serum Testosterone and Mortality in Male Veterans," Archives of Internal Medicine, abstract, Aug. 14/28 (link)

"Testosterone and Aging: Clinical Research Directions," Institute of Medicine, Nov.12, 2003 (link)

American Assn. of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients -- 2002 update (link)

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