Risk of prostate cancer greater in men over 50 with high levels of testosterone

Men over 50 years of age with high blood levels of testosterone have an increased risk of prostate cancer, according to a study by researchers at Johns Hopkins and the National Institute on Aging. The finding throws some doubt on the safety of testosterone replacement therapy, the investigators say.

The researchers measured several forms of testosterone in almost 3,000 blood samples collected over a 40-year period from 759 men in the Baltimore Longitudinal Study on Aging, of whom 111 were diagnosed with prostate cancer. One form of testosterone, called free testosterone, which is biologically active and can actually be used by the prostate, was found to be associated with increased prostate cancer risk, according to J. Kellogg Parsons, M.D., instructor of urology at the Brady Urological Institute at Johns Hopkins and lead researcher of the study.

"Since testosterone replacement therapy increases the amount of free testosterone in the blood, older men considering or receiving testosterone replacement should be counseled as to the association until data from long-term clinical trials becomes available," says Parsons.

The association between free testosterone and prostate cancer risk in older men was not affected by height, weight, percent of body fat, or muscle mass. Total testosterone levels and dehydroepiandrosterone sulfate (DHEAS), another androgenic hormone, were also unrelated to prostate cancer risk, while the protein that binds testosterone in blood, called sex hormone-binding globulin (SHBG), was associated with a slightly decreased risk for prostate cancer.

Higher serum free testosterone is associated with an increased risk of prostate cancer: results from the Baltimore longitudinal study on aging. J. Kellogg Parsons, H. Ballentine Carter, Patricia Landis, E. James Wright, Elizabeth Platz, E. Jeffrey Metter.

Like other steroid hormones testosterone is derived from cholesterol. The largest amounts of testosterone are produced by testes, but it is also synthesized in smaller quantities by the theca cells of the ovaries, the zona reticulosa of the adrenal cortex, and the placenta. Substantial amounts of the testosterone in women are also produced from estradiol by reverse aromatization in the liver, adipose cells, and other peripheral tissues.

In the testes testosterone is produced by the Leydig cells. Due to dual function of the male gonad testosterone directly influences spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone binding globulin (SHBG).

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