Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men

Background: The independent and joint association of metformin and testosterone replacement therapy (TTh) with the incidence of prostate, colorectal, and male breast cancers remain poorly understood, including the investigation of the risk of these cancers combined (HRCs, hormone-associated cancers) among men of different racial and ethnic background.

Methods: In 143,035 men (≥ 65 yrs old) of SEER-Medicare 2007-2015, we identified White (N = 110,430), Black (N = 13,520) and Other Race (N = 19,085) men diagnosed with incident HRC. Pre-diagnostic prescription of metformin and TTh was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models were conducted.

Results: We found independent and joint associations of metformin and TTh with incident prostate (odds ratio [OR]_joint = 0.44, 95% confidence interval [CI]: 0.36-0.54) and colorectal cancers (OR_joint = 0.47, 95% CI: 0.34-0.64), but not with male breast cancer. There were also inversed joint associations of metformin and TTh with HRCs (OR_joint = 0.45, 95% CI: 0.38-0.54). Similar reduced associations with HRCs were identified among White, Black, and Other Race men.

Conclusion: Pre-diagnostic use of metformin and TTh were, independently and jointly, inversely associated with incident prostate and colorectal cancers. The risk of HRCs was also reduced among White, Black and Other Race men. Greatest reduced associations of prostate and colorectal cancers and HRCs were mainly observed in combination of metformin and TTh. Larger studies are needed to confirm the independent and joint association of metformin plus TTh with these cancers in understudied and underserved populations.