Radical Prostates: Female Hormones May Play a Pivotal Role in a Distinctly Male Epidemic
Raloff, Janet, Science News
Estrogen remains one of the strongest and best-characterized risk factors for breast cancer, the second leading cause of cancer deaths in U.S. women. The greater a woman's lifetime exposure to this quintessential female sex hormone, the greater her chance of developing the disease.
Fewer details have emerged to explain breast cancer's counterpart in men-prostate cancer, the most prevalent male malignancy and second leading cause of cancer deaths in men. Prostate cancer afflicts some 50 to 70 percent of men in Western countries by age 70, and the incidence of the disease is on the rise. Each year now, in the United States alone, some 244,000 new cases are diagnosed and 44,000 men die from the cancer.
While physicians have yet to find an effective prevention strategy for prostate cancer, one is "desperately needed," says William G. Nelson of the Johns Hopkins Medical Institutions in Baltimore. Ironically, one of the newer avenues in breast cancer research may offer some unanticipated payoffs here. Growing evidence suggests that both malignancies trace to a common mechanism-damage to DNA. Such damage can be triggered, at least in part, by estrogen.
One observation unites researchers attempting to flesh out this provocative theory: a consistent finding of extensive oxidation in the tissue where prostate cancers form. This oxidation is caused by free radicals-short-lived molecular fragments that damage cellular proteins and DNA by chemically altering them. The magnitude of this oxidative damage increases with age, as does the incidence of prostate cancer.
This free radical model "is a very neglected area in prostate cancer research," according to Shuk-mei Ho, an endocrine oncologist at Tufts University in Medford, Mass. To date, she says, the search for the mechanisms behind this cancer has focused primarily on male sex hormones and their effects on genes.
Yet Ho and others have recently begun demonstrating that hormones can play unexpected roles in this tissue. Indeed, the hostile, free-radical-laden environment that hormones might foster in the prostate could go a long way toward explaining cancer's development there.
The association of free radicals with aging in prostate tissue has already spurred the development of a new, more precise technique not only for diagnosing prostate cancer, but also for finding evidence of the DNA damage that may precede it. New findings in this area suggest that dietary and other antioxidant therapies may hold great promise for curbing this scourge.
Critical to reproduction, the prostate produces the seminal fluid that carries sperm cells. Wrapped around a man's urethra, the tube that carries urine from the bladder, this walnut-sized, muscular gland grows under the influence of testosterone and other male sex hormones, or androgens. Indeed, cancer does not develop in this tissue unless it has access to androgens. However, the notion that androgens alone are responsible for most prostate cancers does not make sense, argues Joachim G. Liehr, a pharmacologist at the University of Texas Medical Branch in Galveston. "If they were," he says, "young men at 18 or 20-the peak of androgen production-should be getting the disease." In fact, he notes, the cancer tends to strike in middle to old age, when testosterone concentrations are waning.
Men's estrogen production, in contrast, does not fall in old age. Indeed, Liehr notes, it may even creep up a bit. Together, these changes cause a dramatic shift in the ratio of testosterone to estrogen, a turn he believes may foster this cancer. That suspicion is shared by Maarten Bosland at the New York University Medical Center in Tuxedo. Though estrogens have been used to treat prostate cancer, he notes that recent animal studies indicate that these hormones may actually enhance testosterone's threat to the prostate.
For instance, Bosland gave young, castrated male rats enough estrogen to produce concentrations equivalent to those naturally present in females. …