Testosterone Replacement Does Not Increase Risk for Prostate Cancer, Cardiovascular Disease

Testosterone replacement therapy does not increase the risk for aggressive prostate cancer or for cardiovascular (CV) disease. In fact, testosterone replacement in men with hypogonadism decreases these risks, according to data presented at the 2016 American Urological Association (AUA) meeting.

A study of a nationwide Swedish database revealed a 50% reduction in risk for aggressive prostate cancer among men who received TRT for >1 year compared with the control group, said Stacy Loeb, MD, Assistant Professor of Urology, New York University Langone Medical Center, who presented the study.

The study examined the association between testosterone replacement and prostate cancer using the National Prostate Cancer Register and the Prescribed Drug Register, which identified 38,570 men with a prostate cancer between 2009 and 2012, and 192,838 men without prostate cancer in the control group.

In each group, 1% of patients were using testosterone replacement. Of the patients, 59% had favorable disease, 38% had aggressive disease, and 3% had missing data on disease severity.

Testosterone replacement was not associated with overall prostate cancer risk, with an adjusted hazard ratio of 1.03.

“The type of testosterone didn’t matter. We looked at whether they used gel, injections, or other types, and there was no difference in prostate cancer risk based on the mode of administration,” said Dr Loeb.

Testosterone replacement increased the risk for favorable prostate cancer by 61% during the first year; however, this may be a detection bias, because Swedish guidelines recommend enhanced screening for prostate cancer in the first year of testosterone replacement. Overall, there was a 50% reduction in the diagnosis of aggressive prostate cancer among TRT users, with no difference in the risk for aggressive prostate cancer during the first year of TRT use.

Among the men receiving testosterone replacement for ≥1 years, the risk was reduced to 31%; after 1 year, a 56% reduction in aggressive prostate cancer was found among testosterone users versus the matched controlled.

Dr Loeb said that previous studies suggest an increased risk for aggressive prostate cancer in men with hypogonadism, and that cancer in a low-testosterone environment tends to be more aggressive.

“Our findings [show] that men who took testosterone in the long-term had fewer aggressive cancers, which suggests that replacing it to normal levels mitigates this risk,” she said.

Testosterone Replacement Reduces Risk for Prostate Cancer and CV Disease

Other studies presented at the meeting confirmed the lack of relationship between testosterone use and the incidence of aggressive prostate cancer. One study showed that men with untreated hypogonadism had an increased risk for a more severe prostate cancer phenotype than men who received testosterone.

Another study showed that testosterone decreased the risk for prostate cancer and for CV events and overall mortality. Christopher Wallis, MD, MSc, Division of Urology, University of Toronto, Ontario, Canada, and colleagues, examined 10,311 patients who had testosterone prescriptions between 2007 and 2012, and 28,029 patients in the control group without such prescriptions.

Testosterone users had a significant 12% reduction in overall mortality, with a 33% reduction among patients with exposure to testosterone in the highest tertile versus the control group. No change was seen in CV among testosterone users compared with the controls, but patients with the highest exposure to testosterone had a 16% reduction in the risk for CV events.

The number of prostate cancer diagnoses was reduced by 14% in the testosterone users cohort and by 40% in those with the highest exposure.

Although the data support the safety of long-term use of TRT, “potential protective effects of testosterone replacement therapy remain to be proven,” said Dr Wallis.

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