Cancer paradox: Testosterone injections combat lethal prostate tumors

Testosterone may be the key to manliness, but it also stokes the growth of prostate cancer cells. So injections of the hormone might sound like the last thing a man with this type of cancer needs. But a new study shows that the shots can slow the progression of untreatable prostate tumors in some patients.
Researchers have known since the 1940s that slashing the levels of testosterone and other male sex hormones can rein in prostate tumors. Today, a common treatment for prostate cancers that have spread to other parts of the body is chemical castration, drugs that cut the body’s production of testosterone and related hormones. But the cancer cells usually adapt to the low hormone levels and resume growing. For example, they sometimes crank out more of the receptor molecules stimulated by testosterone or switch to a version of the receptor that doesn’t need testosterone to prompt growth. Although researchers have devised new treatments to counteract this resistance, such as drugs that block the testosterone receptor, tumors often quickly develop resistance to them as well.
Studies of cancer cells in a dish and tumors in animals have revealed a paradox about so-called castration-resistant prostate cancer. Cancer cells that prosper when testosterone is scarce often die when exposed to high levels of the hormone. Experiments suggest that the extra hormone disrupts DNA duplication and leads to DNA fractures, which can be fatal for a cell. This paradoxical relationship means that testosterone doses could be beneficial against resistant tumors.
Medical oncologist Michael Schweizer, now at the University of Washington, Seattle, and colleagues from the Johns Hopkins University School of Medicine in Baltimore, Maryland, tested this strategy in 16 men whose prostate cancers had become resistant to chemical castration. Most of their tumors had spread, or metastasized. In the study, the men continued to receive chemical castration therapy, but every 28 days the researchers also injected them with testosterone. Each shot spiked blood testosterone levels well above normal, but they gradually declined until they were close to the level produced by chemical castration. The rationale for these oscillations, Schweizer says, is that “you don’t allow prostate cancer cells to get accustomed to one testosterone environment.” The hormone peaks will kill cancer cells that have adapted to low testosterone, whereas the valleys will stifle cells that require testosterone to grow.