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Purpose: This study investigated the risk of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) associated with metformin use. Materials and Methods: We used the database of Taiwan’s National Health Insurance to create 9,833 pairs of ever users and never users of metformin matched on propensity score. They were males with a new diagnosis of type 2 diabetes during 1999–2005. The incidence of LUTS/BPH was calculated from January 1, 2006 until December 31, 2011. We estimated hazard ratios by Cox regression weighted on propensity score. Results: There were 515 incident cases in ever users after a median follow-up of 5.4 years (incidence rate: 11.24 per 1,000 person-years) and 682 cases in never users after 5.2 years (15.92 per 1,000 person-years). The hazard ratio (HR) that compared ever to never users was 0.69 (95% confidence interval [CI], 0.62–0.78). The HRs that compared ever users categorized into quartiles of cumulative duration (67.17 mo) to never users were 1.02 (0.84–1.23), 1.01 (0.86–1.20), 0.57 (0.47–0.69), and 0.40 (0.32–0.49), respectively. For the quartiles of cumulative dose of 2,449.00 g, the respective HRs were 1.03 (0.85–1.24), 0.96 (0.81– 1.13), 0.60 (0.49–0.72), and 0.40 (0.32–0.50). The lower risk was significant in all quartiles of defined daily dose. However, a larger daily dose was associated with a greater risk reduction. There were no significant interactions between metformin and other antidiabetic drugs. Patients who used rosiglitazone and/or pioglitazone without metformin had a significantly higher risk (HR, 1.33; 95% CI, 1.09–1.63) and a combination with metformin attenuated such an adverse impact (HR, 0.78; 95% CI, 0.66–0.91). Conclusions: A significantly lower risk of LUTS/BPH is observed in males with type 2 diabetes who use metformin.

Purpose: This study investigated prostate cancer risk associated with pioglitazone use. Materials and Methods: The Taiwan’s National Health Insurance database was used to create a propensity score-matched cohort of male patients with type 2 diabetes mellitus newly diagnosed in 1999-2005 and aged ≥25 years at baseline. The matched cohort included 20437 ever users and 20437 never users of pioglitazone. The patients were followed up for the incidence of prostate cancer until December 31, 2011. Hazard ratios (HRs) were created from Cox regression weighted on propensity score. Results: Prostate cancer was diagnosed in 121 ever users of pioglitazone (incidence: 175.84 per 100,000 person-years) and 143 never users of pioglitazone (incidence: 216.66 per 100,000 person-years). When ever users were compared to never users of pioglitazone, the HR was 0.815 (95% confidence interval [CI], 0.639–1.039; p=0.0987). When ever users were categorized into tertiles of cumulative duration of pioglitazone therapy (20.23 months), the HRs were 1.044 (95% CI, 0.741–1.471), 0.975 (95% CI, 0.690–1.377) and 0.539 (95% CI, 0.374–0.778), respectively. For the tertiles of cumulative dose of 15,330 mg, the HRs were 1.008 (95% CI, 0.710–1.429), 1.090 (95% CI, 0.785–1.515) and 0.484 (95% CI, 0.330–0.711), respectively. A significantly lower risk associated with pioglitazone use could only be seen in patients aged 20.23 months or a cumulative dose of >15,330 mg. The risk reduction is mainly observed in patients aged

Metformin is the first-line oral antidiabetic drug that shows multiple pleiotropic effects of anti-inflamation, anti-cancer, antiaging, anti-microbia, anti-atherosclerosis, and immune modulation. Metformin’s effects on men’s related health are reviewed here, focusing on reproductive health under subtitles of erectile dysfunction (ED), steroidogenesis and spermatogenesis; and on prostate-related health under subtitles of prostate specific antigen (PSA), prostatitis, benign prostate hyperplasia (BPH), and prostate cancer (PCa). Updated literature suggests a potential role of metformin on arteriogenic ED but controversial and contradictory effects (either protective or harmful) on testicular functions of testosterone synthesis and spermatogenesis. With regards to prostate-related health, metformin use may be associated with lower levels of PSA in humans, but its clinical implications require more research. Although there is a lack of research on metform’s effect on prostatitis, it may have potential benefits through its anti-microbial and anti-inflammatory properties. Metformin may reduce the risk of BPH by inhibiting the insulin-like growth factor 1 pathway and some but not all studies suggest a protective role of metformin on the risk of PCa. Many clinical trials are being conducted to investigate the use of metformin as an adjuvant therapy for PCa but results currently available are not conclusive. While some trials suggest a benefit in reducing the metastasis and recurrence of PCa, others do not show any benefit. More research works are warranted to illuminate the potential usefulness of metformin in the promotion of men’s health.