麻豆传媒

SAN DIEGO -- Examination of a national health database failed to find a relationship between testosterone replacement therapy (TRT) and prostate cancer risk. In fact, over the long term, a reduction in the risk of aggressive prostate cancer was observed in men treated with TRT, similar to previous observations.

The analysis uncovered a halving of the risk of aggressive prostate cancer with TRT when used for more than 1 year compared with controls. The findings were presented by , from the New York University Langone Cancer Center, New York City, at the 2016 annual meeting of the .

The study population consisted of 38,570 prostate cancer cases diagnosed between 2009 and 2012 from the National Prostate Cancer Register of Sweden. Serving as controls were 192,838 men matched on birth year and place of residence. These databases were linked to the Prescribed Drug Register of Sweden, which allowed the researchers to obtain information on the type, dose, and duration of TRT.

Of the 38,570 prostate cancer cases, 284 had used testosterone at some point before their prostate cancer diagnosis. Of the men with prostate cancer, 59% had favorable disease and 38% had aggressive disease. Of the 192,838 controls, 1,378 had used testosterone. The median age was 69 years in both groups.

No association was found between TRT and the overall risk of prostate cancer when adjusted for comorbidity, marital status, and level of education.

"The type of testosterone didn't matter," said Loeb. "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."

When examined by risk group, TRT users had an increased risk of being diagnosed with favorable prostate cancer (OR 1.35, 95% CI 1.16-1.56). The greatest risk of being diagnosed with favorable disease occurred within the first year of TRT use, which suggests detection bias, she said, since guidelines in Sweden recommend enhanced screening for prostate cancer during the first year of TRT use.

TRT was associated with a 50% reduction in the risk of aggressive prostate cancer, "and this became much stronger and significant in long-term use," similar to the findings in other series, she said.

Speculating on the mechanism behind the large reduction in risk of aggressive disease with long-term TRT use, Loeb pointed to a large body of literature that suggests that hypogonadal men have more aggressive disease. Activation of prostate tumor-promoting pathways and genetic changes have been observed in a low testosterone environment, she said.

"We hypothesize that for these men, restoring them back to normal testosterone levels may mitigate the risk of what seems to be a more aggressive phenotype of tumors developing in a low testosterone environment."

, a urology and andrology specialist in Bremerhaven, Germany, and colleagues also found that TRT in hypogonadal men does not increase the risk of prostate cancer. His group looked at registry data from 656 symptomatic hypogonadal men (total testosterone levels ≤348 ng/dL) with a mean age of 61 years. Some 360 men received parenteral testosterone undecanoate, dosed at 1,000 mg/12 weeks following an initial 6-week interval, for up to 10 years. The other 296 men who opted against TRT served as controls.

Both groups were followed for a mean of 78.0 months. The proportion diagnosed with prostate cancer over this time was 1.9% in the TRT group and 4.1% in the controls. The incidence of prostate cancer per 10,000 patient years was found to be 31 in the TRT group compared with 64 in controls. Of those in the TRT group who developed prostate cancer, 100% had a Gleason score ≤3, compared with only 25% of the controls, again suggesting a more severe phenotype without TRT. Two-thirds of untreated controls who had prostate cancer had Gleason 4 disease, and 42% had positive surgical margin, noted Haider.

"Hypogonadism by itself may increase the rate of high-grade prostate cancer."

A third study confirmed the lack of relationship between TRT and incident prostate cancer in hypogonadal men, this one an analysis of U.S. veterans reported by , at the University of Washington in Seattle.

Almost 15,000 U.S. veterans with laboratory-defined low testosterone formed the study population. Some 40% of the men received either intramuscular TRT, topical TRT, or both. Sixty percent received no testosterone treatment. The median follow-up for the entire cohort was 3 years.

About 1% of the men were diagnosed with prostate cancer, and of these, 22% were aggressive cancers. The incidence of all prostate cancer per 1,000 person-years was 2.52 in the men treated with TRT and 2.78 in those not treated.

The adjusted risk of all prostate cancer was not significantly different between treated and untreated men (HR 0.90, 95% CI 0.81-1.10), and neither was the risk of aggressive prostate cancer (HR 0.89, 95% CI 0.70-1.13). The results did not change significantly when assessing TRT by the formulation of testosterone.

"I would not look at this and say there is a protective effect of testosterone," said Walsh. "I think there is evidence for absence of risk, but I would not call this evidence of protection."