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No Link Seen Between Testosterone and Prostate Cancer Risk

— Meta-analyses find testosterone -- endogenous or supplemented -- is not associated with PSA levels.

Last Updated May 21, 2015
MedpageToday

NEW ORLEANS -- Endogenous serum testosterone levels are not associated with prostate-specific antigen (PSA) levels or the risk of developing prostate cancer, nor is testosterone replacement therapy (TRT) for symptomatic hypogonadism, according to two separate multicenter, multinational meta-analyses presented here.

The data were presented by Peter Boyle, MD, of the in Ecully, France, during a press briefing at the .

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Neither endogenous testosterone levels nor supplemental testerone therapy for symptomatic hypogonadism are associated with PSA levels or risk of prostate cancer according to meta-analyses.
  • Transdermal testosterone therapy alone is similarly unassociated with PSA levels or prostate cancer.

"Many urologists are concerned that TRT may accelerate prostate growth not only in benign disease but also in cancer," according to Boyle. The thinking is that because most prostate cancers respond to androgen deprivation therapy (until they establish an androgen-independent growth mechanism), testosterone may act to stimulate prostate growth and prostate cancer.

To explore these relationships further, Boyle and co-investigators undertook two meta-analyses. The first examined 20 estimates obtained from 18 publications for serum testosterone and prostate cancer risk.

The summary relative risk for the highest versus the lowest quantile of serum testosterone in the analysis was 0.98 (95% CI 0.88-1.09), "which is as close to 1.0 as you can generally get in any sort of meta-analysis," said Boyle. There was no heterogeneity in the study's findings and no evidence of publication bias. "Testosterone in the serum doesn't have anything at all to do with determining the risk of prostate cancer," he declared.

Boyle and colleagues then looked at TRT, finding 24 studies that produced unique estimates of the change in PSA levels after the onset of replacement or supplemental therapy. The overall difference in the PSA level was 0.11 ng/mL (95% CI -0.23 to 0.46). There was again no evidence of heterogeneity nor publication bias.

When applying a correction factor for the normal variation in PSA observed in men with initially low PSA levels, the overall difference was again not statistically significant.

And when the analysis was restricted to the 12 studies in which TRT was delivered in a transdermal fashion, none of the individual studies produced a statistically significant increase in the PSA level, and the overall difference in PSA level derived from the meta-analysis was 0.23 ng/mL, which again was far from being statistically significant.

"When the correction factor was applied, the overall difference in PSA level was again found to be not statistically significant, and even closer to 0 than without the correction factor," Boyle said. "The overall meta-analysis demonstrated no significant difference in PSA level between the beginning of the use of TRT until it was ceased."

A total of 11 studies produced unique estimates of the risk of prostate cancer associated with the use of TRT. None of the individual studies suggest a statistically significant increased risk of prostate cancer in the TRT arms compared with the control arms, with a summary odds ratio of 0.94 (95% CI 0.37-2.40).

When restricting the analysis to the seven studies in which the TRT was delivered in a transdermal route, none of the individual studies produced a statistically significant increased risk of prostate cancer with TRT.

"Available data do not support an increase in the risk of prostate cancer associated with TRT, nor do they support a change in PSA level when TRT is used," said Boyle. "In particular, these findings also apply when consideration is restricted to situations where TRT is delivered by a transdermal route."

Fifty years ago, there was an assertion that testosterone and prostate cancer were invariably linked, and that increased testosterone would make prostate cancer worse, said press briefing moderator , of Southern Illinois University.

These meta-analyses highlight the lack of definitive data linking testosterone and progression of prostate cancer or causation of prostate cancer, he said, calling them "reassuring in that they show no change in PSA or prostate cancer risk."

Disclosures

Partial funding for the study was provided by Repros Therapeutics.

No author reported benefiting from this source of funding.

Primary Source

American Urological Association

Source Reference: Boyle P, et al "Endogenous and exogenous testosterone and the risk of prostate cancer and prostate-specific antigen" AUA 2015; Abstract MP4-09.