MICHAEL BRYANT / Staff Photographer
Prescriptions for medications such as Testim and AndroGel have soared into the millions.
Hormone boosts for men get a test
Concerned that American men may be embracing the same kind of misguided sex-hormone use that brought calamity to women, the government is funding a national study to see whether older men with low testosterone benefit from boosting it.
Led by University of Pennsylvania endocrinologist Peter Snyder, the $45 million clinical trial, which this month began recruiting 800 men older than 64, is by far the largest ever to compare the effects of the quintessential male hormone with a placebo. It will investigate whether in some men, symptoms of aging such as ebbing energy, limp libido, and muddy memory are partly due to testosterone deficiency.
It is, Snyder said, an "unprecedented opportunity" to shed light on the question: Is unusually low testosterone pathological, or just a natural part of aging?
Still, sponsors say, the "T Trial" (the logo is a T inside a male symbol) will not follow enough men for enough years to settle larger questions such as: What are the risks? And could younger, healthier men benefit from heightened T?
Millions of them are not waiting for answers. Sales of male hormone products, worth $809 million last year, keep rising, a trend that worried experts say justifies public investment in careful studies.
"Viewed by some as an antiaging tonic, the growth in testosterone's reputation and increased use by men of all ages in the United States has outpaced the scientific evidence," concluded an Institute of Medicine expert panel that recommended the new research.
In 2002, when a 15-year-long, $725 million government trial called the Women's Health Initiative showed that menopausal hormone therapy was risky for female hearts, blood vessels, brains, and breasts, women and doctors were stunned.
After all, a vast body of research showed that estrogen's cardiovascular and bone benefits outweighed the slightly increased chance of breast cancer. Population studies, risk-factor studies, even many small placebo-controlled trials showed this.
The lesson of the WHI was that a mammoth, long, costly, rigorous trial - the kind drug companies have no incentive to do - was the only way to tease out rare but real risks.
Although the WHI remains subject to criticism, it was definitive enough that, practically overnight, it put an end to routine, long-term menopausal hormone "replacement," and returned estrogen to a hot-flash remedy.
It also left Wyeth Pharmaceuticals, now owned by Pfizer Inc., with thousands of lawsuits linking its leading hormone brand to breast cancer. Just last week, two more women were awarded a total of $100 million.
Now the male tale. In 2002, when the National Institute on Aging announced plans for a 6,000-men, $100 million trial - not a Men's Health Initiative, but close - there was an uproar. Unlike estrogen's research record, testosterone's was scant and inconsistent. No one had proved it prevented or relieved anything in aging men, so trying to tease out the dangers was premature.
Institute of Aging officials "ran into some internal political problems," Snyder recalled. "They were accused of risking men's health."
So they asked the Institute of Medicine - an independent, authoritative scientific advisory group - to weigh in.
Its panel reviewed all available research, then recommended midsize trials. If these show no benefits, the panel said, then larger versions "are not indicated."
Six years later, the T Trial is finally up and running at 12 medical centers across the country. (Penn is the coordinating center, but not an enrollment site. See www.ttrial.org)
The design addresses a number of sticking points, including the fact that experts can't even agree about what "low" testosterone is.
Testosterone levels in the blood fluctuate widely depending on the time of day, and measurement methods vary in accuracy. Men who are obese or have diabetes tend to have depressed levels. And a study of middle-class Californians found almost half who were older than 50 fell below the generally accepted "low" threshold of 300 ng/dl (nanograms of testosterone per deciliter of blood), suggesting it's fairly normal.
Also, testosterone declines gradually but not dramatically with age, unlike estrogen, which plummets to a dribble around age 50.
That's why the whole notion of "andropause" - male menopause - remains controversial.
