Male
Hormone Therapy Popular but Untested
By GINA
KOLATA
 ast
month the government halted a major study of hormone replacement
therapy in healthy women, saying the treatment under study seemed to
do more harm than good. But while that action generated headlines
and alarm, few people noticed just a few weeks earlier when the
government decided not to go ahead with a different study of hormone
replacement — in older men.
The hormone is testosterone, and its use is soaring. Doctors
wrote 1.5 million prescriptions for testosterone and drugs like it
in 2001, up from 806,000 in 1997. The hormone has been trumpeted as
a possible antidote for aging and a way to get a lean and muscular
body.
But while the theory is that testosterone may help counter the
effects of aging — bone and muscle loss, diminished libido — those
effects have never been demonstrated in a large clinical trial. As a
result, medical experts say, men taking the drug are participating
in a vast, uncontrolled medical experiment.
The case for testosterone replacement rests on well-known
observations: as men grow old, their testosterone levels decline; at
the same time, they lose muscle and bone, their sex drive dwindles,
and they may experience depression or failing memory.
In younger men with medical conditions that rob them of
testosterone, such symptoms disappear when they get the drug. So,
some doctors ask, why not give it to older men too?
But testosterone can fuel the growth of prostate cancer, and it
increases red blood cell production, possibly increasing the risk of
clots that can cause heart attacks and strokes. Those risks, with
concerns about the cost, prompted the government in late June to
scuttle a proposed six-year study of testosterone replacement. In
the absence of such a study, answers about testosterone's risks and
benefits may be a long time coming.
"The only thing we ever learn from medical history is that we
never learn," said Dr. John B. McKinlay of the New England Research
Institutes in Watertown, Mass. Dr. McKinlay is the director of the
Massachusetts Male Aging Study, a federally supported study that
follows more than 1,700 men as they age. "On the slimmest of
evidence we introduced estrogen to women," he said, "and the public
was whipped up to ask for it."
Referring to the large clinical trial of hormone therapy in women
that was halted last month, Dr. McKinlay added: "We ended up,
finally, after everyone was getting it, with 45 million
prescriptions in the U.S. each year. And suddenly we find that not
only does it not do what it is supposed to do but there are these
untoward consequences.
"We are about to repeat that debacle. We have the slimmest
evidence on testosterone replacement. Five men here, 10 men there.
Six rats and a partridge in a pear tree. The physiology is not there
but the industry, the industry is there."
Dr. Richard Hodis, director of the National Institute on Aging,
also expressed concern. "We recognize this as a potentially
important public health issue," Dr. Hodis said. "In understanding
the role of testosterone replacement, we are in many ways where we
were decades ago with estrogen replacement with women. It is clear
that we do not know enough to inform men and their doctors on the
potential advantages or risks of hormone replacement."
Nevertheless, some doctors say testosterone deficiency is a real
medical condition that needs treatment. "To say it doesn't exist is
to put your head in the sand," said Dr. Larry Lipshultz, a professor
of urology at Baylor College of Medicine. "The question on the table
is, Can we prescribe this medication enthusiastically without having
good controlled studies?
"My response is that I am still going to use this drug," he went
on. "There is no reason to withhold treatment from patients with
symptoms and lab reports of low testosterone levels because someone
has not done a placebo-controlled study."
The quest to use so-called testicular extracts as a fountain of
youth began with a memorable experiment. On June 1, 1889, a
72-year-old French physiologist, Charles Édouard Brown-Séquard,
reported to spellbound doctors at a medical meeting that he had
injected himself with a substance extracted from the testicles of
dogs and guinea pigs. The injections, he said, "had increased his
physical strength and intellectual energy, relieved his constipation
and even lengthened the arc of his urine," said Dr. John Hoberman, a
historian of science at the University of Texas.
Instantly, a market was born. "All the hucksters jumped on that,"
Dr. Hoberman said.
By 1918, Dr. Leo L. Stanley, the prison doctor at San Quentin,
was transplanting testicles from executed prisoners into healthy
ones, asserting that the treatment restored health and potency.
Soon, Dr. Stanley was substituting testicles from rams, goats and
deer, and contending they were just as effective. Hundreds of
patients sought him out. His papers appeared in the prestigious
journal Endocrinology.
By 1935, scientists had isolated testosterone itself.
"From that point on, you have the real thing," Dr. Hoberman said.
It was the start of a new era, with doctors giving testosterone to
women to treat breast cancer, to athletes to increase their muscle
mass, to homosexuals to "cure" their sexual orientation, to trauma
patients to increase their blood cell production and to healthy men
to counteract aging.
On April 15, 1939, The Journal of the American Medical
Association published a paper called "The Male Climacteric." The
recommended treatment was testosterone therapy. "Testosterone had
just come on the market," Dr. Hoberman said. "You tell me if it was
an accident that we suddenly had a male menopause."
For decades, the therapy involved painful injections into muscle.
A patch was introduced in the mid-1990's, but even it sometimes
caused skin irritation, and some men did not like such a visible
sign that they were taking testosterone.
That changed in June 2000, when Unimed Pharmaceuticals, a
subsidiary of Solvay Group, a Belgian firm, began selling Androgel,
a testosterone preparation that a man could simply rub on his skin.
"It's like putting on sunblock if you're going to the beach," said
Dr. William Crowley, a professor of medicine at Harvard Medical
School.
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