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Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study.

ABSTRACT: Benign Prostate Hyperplasia (BPH) has been associated with prostate cancer prevalent among men after 50 years of age, however, it is unclear whether the antidiabetic drug, metformin, can reduce prostate cancer for men with BPH. The insurance claims data of men aged 50 years or older, with both type 2 diabetes mellitus (T2DM) and BPH diagnosed from 1997 to 2007 were analyzed. Individuals were followed up for at least 5 years. We identified 2906 and 2906 patients as the metformin cohort and nonmetformin cohort, respectively. The Cox method analysis showed that the metformin cohort had an adjusted hazard ratio (aHR) of 0.69 (95% confidence interval [CI] = 0.49-0.96, P = 0.0298) for prostate cancer, compared to the nonmetformin cohort after controlling for age, traditional Chinese medicine (TCM) use, prostate specific antigen, and Charlson comorbidity index. Patients using TCM for BPH (per 6 months) also had an aHR of 0.41 (95% CI = 0.24-0.69; P = 0.0009). In conclusion, both metformin medication and TCM use could be associated with reduced risk of prostate cancer for men with BPH and diabetes.

SUBMITTER: Kuo YJ

PROVIDER: S-EPMC6536940 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study.

Kuo Yu-Jui YJ Sung Fung-Chang FC Hsieh Po-Fan PF Chang Hui-Ping HP Wu Kun-Ling KL Wu Hsi-Chin HC

Cancer medicine 20190409 5

Benign Prostate Hyperplasia (BPH) has been associated with prostate cancer prevalent among men after 50 years of age, however, it is unclear whether the antidiabetic drug, metformin, can reduce prostate cancer for men with BPH. The insurance claims data of men aged 50 years or older, with both type 2 diabetes mellitus (T2DM) and BPH diagnosed from 1997 to 2007 were analyzed. Individuals were followed up for at least 5 years. We identified 2906 and 2906 patients as the metformin cohort and nonmet ...[more]

PMID: 30968600

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Project description:Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is unclear whether such risk is similar to that for another 5α-reductase inhibitor, dutasteride. We aimed to assess the risk of suicidal behaviours with finasteride relative to dutasteride. A nationwide cohort study was conducted using the French National Health Data System (SNDS). Men aged 50 years or older initiating finasteride 5 mg or dutasteride 0.5 mg in France between 01-01-2012 and 30-06-2016 were included and followed until outcome (suicide death identified from death certificate or self-harm hospitalisation), treatment discontinuation or switch, death, or 31-12-2016. Self-harm by violent means or resulting in admission to an intensive care unit were also examined. Cox proportional hazards models controlled for age and psychiatric and non-psychiatric conditions by inverse probability of treatment weighting (IPTW). Analyses were stratified according to psychiatric history. The study compared 69,786 finasteride new users to 217,577 dutasteride new users (median age: 72.0 years [Q1-Q3 = 64.5-80.2] vs. 71.1 [Q1-Q3 = 65.0-79.2]). During follow-up, 18 suicide deaths (0.57/1000 person-years) and 34 self-harm hospitalisations (1.08/1000) occurred among finasteride users versus 47 deaths (0.43/1000) and 87 hospitalisations (0.79/1000) among dutasteride users. Overall, finasteride was not associated with an increased risk of any suicidal outcome (IPTW-adjusted Hazard Ratio = 1.21 [95% Confidence Interval .87-1.67]), suicide death or self-harm hospitalisation. However, among individuals with a history of mood disorders, finasteride was associated with an increased risk of any suicidal outcome (25 versus 46 events; HR = 1.64 [95% CI 1.00-2.68]), suicide death (8 versus 10 events; HR = 2.71 [95% CI 1.07-6.91]), self-harm by violent means (6 versus 6 events; HR = 3.11 [95% CI 1.01-9.61]), and self-harm with admission to an intensive care unit (7 versus 5 events; HR = 3.97 [95% CI 1.26-12.5]). None of these risks was significantly increased among individuals without a psychiatric history. These findings do not support an increased risk of suicide with finasteride used in the treatment of benign prostatic hyperplasia. However, an increased risk cannot be excluded among men with a history of mood disorder, but this result based on a limited number of events should be interpreted with caution.

Project description:BackgroundThe association between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remains controversial, largely due to a detection bias in traditional observational studies.ObjectiveTo assess the association between BPH and PCa using inherited single nucleotide polymorphisms (SNPs).Design setting and participantsThe participants were White men from the population-based UK Biobank (UKB).Outcome measurements and statistical analysisThe association between BPH and PCa was tested for (1) phenotypic correlation using chi-square, (2) genetic correlation (r g) based on genome-wide SNPs using linkage disequilibrium score regression, and (3) cross-disease genetic associations based on known risk-associated SNPs (15 for BPH and 239 for PCa), individually and cumulatively using genetic risk score (GRS).Results and limitationsAmong 214 717 White men in the UKB, 24 623 (11%) and 14 311 (6.7%) had a diagnosis of BPH and PCa, respectively. Diagnoses of these two diseases were significantly correlated (χ2 = 1862.80, p < 0.001). A significant genetic correlation was found (r g = 0.16; 95% confidence interval 0.03-0.28, p = 0.01). In addition, significant cross-disease genetic associations for established risk-associated SNPs were also found. Among the 250 established genome-wide association study-significant SNPs of PCa or BPH, 49 were significantly associated with the risk of the other disease at p < 0.05, significantly more than expected by chance (N = 12, p < 0.001; χ2 test). Furthermore, significant cross-disease GRS associations were also found; GRSBPH was significantly associated with PCa risk (odds ratio [OR] = 1.26 [1.18-1.36], p < 0.001), and GRSPCa was significantly associated with BPH risk (OR = 1.03 [1.02-1.04], p < 0.001). Moreover, GRSBPH was significantly and inversely associated with lethal PCa risk in a PCa case-case analysis (OR = 0.58 [0.41-0.81], p = 0.002). Only White men were studied.ConclusionsBPH and PCa share common inherited genetics, which suggests that the phenotypic association of these two diseases in observational studies is not entirely caused by the detection bias.Patient summaryFor the first time, we found that benign prostatic hyperplasia and prostate cancer are genetically related. This finding may have implications in disease etiology and risk stratification.

Dataset Information

Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study.

Publications

Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study.

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