Untreated hypogonadism and testosterone replacement therapy in hypogonadal men are associated with a decreased risk of subsequent prostate cancer: a population-based study.

The study identified 3,222,904 men who met inclusion criteria, with 50% diagnosed with hypogonadism matched to eugonadal controls.

• 1,611,452 men were diagnosed with hypogonadism and each were matched to a eugonadal control (1,611,452).
• Data were derived from the Merative MarketScan database of commercial claims encounters.
• Multivariate negative binomial regression analysis was used, adjusting for various known confounding factors.

The incidence of prostate cancer differed significantly across the three groups: eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT.

• Prostate cancer incidence was 2.16% in eugonadal controls, 1.55% in hypogonadal men on TRT, and 1.99% in hypogonadal men without TRT.
• The difference across groups was statistically significant (p < 0.001).
• Hypogonadal men on TRT had the lowest overall prostate cancer incidence of the three groups.

Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer compared to eugonadal controls.

• IRR 0.46 (95% CI 0.43–0.50, p < 0.001) for untreated hypogonadal men versus eugonadal controls.
• This represents approximately a 50% decreased incidence of localized prostate cancer.
• The association was independent after adjusting for known confounding factors.

Hypogonadal men on TRT had a significantly decreased risk of localized prostate cancer compared to eugonadal controls.

• IRR 0.49 (95% CI 0.45–0.53, p < 0.001) for hypogonadal men on TRT versus eugonadal controls.
• The magnitude of decreased risk for localized prostate cancer was similar between treated (IRR 0.49) and untreated (IRR 0.46) hypogonadal men.
• TRT did not appear to restore prostate cancer risk to the level seen in eugonadal controls.

Both untreated hypogonadism and TRT-treated hypogonadism were associated with an approximately 80% decreased risk of metastatic prostate cancer compared to eugonadal controls.

• Hypogonadal men on TRT had an IRR of 0.21 (95% CI 0.19–0.24, p < 0.001) for metastatic prostate cancer.
• Untreated hypogonadal men had an IRR of 0.20 (95% CI 0.18–0.22, p < 0.001) for metastatic prostate cancer.
• The risk reduction for metastatic prostate cancer (~80%) was greater in magnitude than that observed for localized prostate cancer (~50%) in both hypogonadal groups.