A small study found that testosterone may suppress the growth of some advanced prostate cancers and could reverse resistance to testosterone-blocking agents.
Testosterone has been found to suppress the growth of some advanced prostate cancers and may also be able to reverse the resistance to prostate cancer drugs that suppress testosterone production. The findings are surprising, since testosterone is generally known to provide fuel for prostate tumor growth.
The small 16-patient pilot study treated men with asymptomatic metastatic prostate cancer, who had rising prostate-specific antigen (PSA) levels and evidence of resistance to androgen deprivation therapy (ADT), with three 28-day cycles of testosterone and 2 weeks of the chemotherapy etoposide. The patients who had declining PSA levels after three cycles continued to receive testosterone injections alone.
The results of the study were published in Science Translational Medicine.
Seven of the men had 30% to 99% decreases in PSA levels. Four of these men stayed on therapy for 1 to 2 years and had steady low PSA levels. Of the remaining nine men, seven had no changes in their PSA levels, one died due to pneumonia and sepsis from the chemotherapy treatment, and one did not complete the study due to prolonged erection from the testosterone.
Ten men underwent imaging scans to measure their disease-five of these men had tumor shrinkage of more than 50%, including one whose cancer was no longer detectable by imaging. “Surprisingly, we saw PSA reductions in all of 10 men, including four whose PSA didn’t change during the trial, who were given testosterone-blocking drugs after the testosterone treatment,” said lead author Samuel Denmeade, MD, medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine in Baltimore, in a statement.
ADT, which blocks the interaction between the testosterone androgen and its receptors, is the mainstay treatment for metastatic prostate cancer. But, most men eventually develop resistance to ADT or primary castration. Resistance develops mainly through overexpression and amplification of the androgen receptor or through mutations of the receptor to a constitutively active form.
ADT may make prostate tumors more aggressive, resulting in resistance to any attempt to block androgen receptors. But, exposure to levels of testosterone much greater than those normally made in the body has been shown to inhibit the growth of androgen receptor–dependent castration-resistant prostate cancer (CRPC) cell lines. Denmeade and colleagues tested the hypothesis that a large influx of testosterone may result in the tumor cells producing fewer androgen receptors, which could make the cells vulnerable to ADT.
According to Denmeade, the timing to give testosterone therapy is important but not easy to determine, and he warns against self-medication with over-the-counter testosterone supplements. Taken incorrectly and at the wrong time, testosterone can lead to worsening of the disease.
The testosterone therapy was given at irregular intervals, resulting in alternating low and high levels of testosterone. The chemotherapy treatment resulted in nausea, hair loss, fatigue, edema, and neutropenia. Men who received only testosterone had low-grade adverse events, with only four men experiencing side effects. Most side effects from testosterone therapy were grade 1; the exceptions were grade 2 events of hair loss and an elevated creatinine in one patient and grade 2 nausea in another patient. Men who had normal sexual function prior to ADT had restored sexual function and libido following testosterone therapy.
All 10 patients who were evaluated by imaging received ADT following testosterone therapy and had PSA reductions, “suggesting that [testosterone therapy] may also restore sensitivity to ADTs,” stated the authors. They concluded that testosterone therapy “shows promise as treatment for CRPC and should be further evaluated in larger trials.”
According to the authors, more studies to test the role of testosterone in CRPC are being planned at Johns Hopkins University and other institutions.