By researchers' estimates, more than a half-million American men with prostate cancer take drugs that radically lower their testosterone levels, effectively castrating them.
Called androgen deprivation therapy, the drugs unquestionably help those with advanced prostate cancer, their benefits far outweighing side effects that can include loss of libido, hot flashes, weight gain, and heightened risk of heart disease.
But the hormone therapy is also increasingly prescribed for the growing number of men whose cancer is detected at an earlier stage or poses less obvious danger. And among them, many -- if not most -- "receive it in situations for which there is no proven clinical benefit," said Dr. Matthew Smith, an oncologist at Massachusetts General Hospital.
If the upside for a given man is unclear, he said, "then the side-effect considerations become paramount."
Because prostate cancer is so slow-growing, many men, once diagnosed are told to do nothing but "watch and wait " for it to progress. But specialists and researchers say it is difficult for doctors and cancer patients to simply sit back. So a growing number of doctors prescribe androgen deprivation, which is seen as less drastic than surgery or radiation, the other standard treatments.
In other cases, men start the drugs when, after surgery, their scores on a prostate cancer blood test start climbing -- even though it is far from clear, researchers say, that such intervention is medically beneficial.
In a study of 73,000 Medicare patients with prostate cancer, Smith and colleagues reported that men who took the hormone-blocking drugs appeared to run a significantly greater risk of developing diabetes and a somewhat higher risk for heart disease. The risks rose within months of starting treatment.
Other studies have found that androgen deprivation carries a wide array of potential side effects, putting the men through something like female menopause -- and then some. The treatment blocks testosterone production by the testes, amounting, doctors say, to medical castration.
"It's possible that some people could be harmed more by the therapy than by the actual cancer, and that's the concern," said Dr. Vahakn Shahinian of the University of Michigan, who studies the use of hormone therapy.
Though 1 in 6 men is diagnosed with prostate cancer, only 1 in 34 dies of it.
Most prostate cancers are slow-growing and strike older men, who will probably die of something else.
Smith estimates that perhaps 650,000 American men take androgen-deprivation therapy, and several other specialists said that estimate seems reasonable.
Well-established research shows that the drugs improve a man's chances both in advanced or high-risk cases, and when combined with radiation therapy.
But the rising use of hormone therapy clearly extends far beyond those cases. Of all the men on hormone therapy, probably only between one-third and one-half have solid medical research backing up their choice, Shahinian and Smith estimated.
Shahinian's research has found that among men with the earliest stage of the disease -- whose cancer is well-contained within the prostate -- the percentage who go on hormone therapy rose from about 2 percent in the early 1990s to between 10 and 15 percent by the end of the decade. Even among men over 80 with relatively low-risk cancer, the percentage on hormone therapy grew from about 4 percent in 1991 to about 31 percent in 1999, one study found.
Androgen deprivation is particularly tempting, researchers say, because it reliably and dramatically improves a man's score on the prostate-specific antigen, or PSA test -- the blood test that is often the first sign of cancer and is used to monitor the disease after diagnosis.
Profit, too, may play a role in the therapy's popularity, specialists and researchers say, though no studies have nailed it down.
The drugs, sold under names like Lupron, Zoladex, Eligard , and Vantas, are big business for both the companies that make them and the urologists who administer them -- at about $1,000 for a shot that lasts three months. Some men go on the drugs only for a few months, but others stay on them for many years.
(In recent years, TAP Pharmaceutical Products has had to pay more than $1 billion to resolve charges and compensate consumers for illegal marketing practices connected with its sales of Lupron.)
Exactly when androgen therapy should be used remains a topic of major debate among urologists and oncologists.
But at the very least, specialists say, patients should make sure they are fully informed of the potential side effects before they start taking the drugs. A patient should make sure the risk-benefit ratio makes sense for him, and have a good question-and-answer session with his doctor, said Dr. Paul Schellhammer, a urology professor at Eastern Virginia Medical School in Norfolk, Va.
Part of the difficulty of calculating that risk-benefit ratio is that few men on androgen deprivation therapy hear the full story on side effects in advance from their doctors or their peers, said Richard Wassersug, a professor of anatomy and neurobiology at Dalhousie Medical School in Nova Scotia.
When Wassersug was prescribed androgen deprivation therapy several years ago, he researched the possible side effects in advance -- but even with that warning, he was amazed at how powerful they were. Hot flashes and soaking night sweats disturbed his sleep; he lost his car in a parking lot for the first time in his life; his libido disappeared, as did his body hair.
"You're going through menopause in a matter of a few days or weeks," he said. Men on androgen deprivation "are depressed, not talking to their spouses, not exercising, losing lean muscle mass, putting on weight, developing diabetes."
He later switched to a female hormone, estradiol, which would equally suppress his testosterone but at least give him some sex hormones to keep his brain working more normally, said Wassersug, adding that he does not regret taking the drugs.
Joel Samuels of Boston, whose prostate cancer was diagnosed in 1994, has heard men debate the hormone therapy question for years at support groups, and been on the drugs himself for about four years.
His side effects have been unremarkable, he said, but every man is different, and must weigh the pros and cons: "You have to be in charge of your own destiny," he said.
Carey Goldberg can be reached at firstname.lastname@example.org