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

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          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.

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          Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial.

          Takuma Higurashi, Kunihiro Hosono, Hirokazu Takahashi … (2016)
          The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence.
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            Prospective study of sex hormone levels and risk of prostate cancer.

            P H Gann, C H Hennekens, J Ma … (1996)
            Sex steroids, particularly androgens, have been implicated in the pathogenesis of prostate cancer. Data from previous studies comparing circulating hormone levels in men with and without prostate cancer are difficult to interpret, since the studies were limited in size, hormone levels were analyzed in blood drawn after the diagnosis of cancer, nonrepresentative control subjects were used, and hormone and hormone-binding protein levels were not simultaneously adjusted. We conducted a prospective, nested case-control study to investigate whether plasma hormone and sex hormone-binding globulin (SHBG) levels in healthy men were related to the subsequent development of prostate cancer. Among participants in the Physicians' Health Study who provided plasma samples in 1982, we identified 222 men who developed prostate cancer by March 1992. Three hundred ninety control subjects, matched to the case patients on the bases of age, smoking status, and length of follow-up, were also identified. Immunoassays were used to measure the levels of total testosterone, dihydrotestosterone (DHT), 3 alpha-androstanediol glucuronide (AAG), estradiol, SHBG, and prolactin in the stored (at -82 degrees C) plasma samples. Correlations between individual hormone levels and between hormone levels and SHBG in the plasma of control subjects were assessed by use of Spearman correlation coefficients (r). Odds ratios (ORs) and 95% confidence intervals (CIs) specifying the prostate cancer risk associated with quartile levels of individual hormones, before and after adjustment for other hormones and SHBG, were calculated by use of conditional logistic regression modeling. Reported P values are two-sided. No clear associations were found between the unadjusted levels of individual hormones or SHBG and the risk of prostate cancer. However, a strong correlation was observed between the levels of testosterone and SHBG (r = .55), and weaker correlations were detected between the levels of testosterone and the levels of both estradiol (r = .28) and DHT (r = .32) (all P 2.5 ng/mL) were excluded from the analyses. High levels of circulating testosterone and low levels of SHBG-both within normal endogenous ranges-are associated with increased risks of prostate cancer. Low levels of circulating estradiol may represent an additional risk factor. Circulating levels of DHT and AAG do not appear to be strongly related to prostate cancer risk.
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              BPH: epidemiology and comorbidities.

              Kevin T. McVary (2006)
              Recently published data suggest that clinical benign prostatic hyperplasia (BPH), which is hallmarked by the occurrence of moderate-to-severe lower urinary tract symptoms (LUTS), occurs in about one quarter of men in their 50s, one third of men in their 60s, and about half of all men 80 years or older. Although effective treatments for LUTS/BPH are available, this condition often occurs in the context of common, age-related comorbidities such as cardiovascular disease, hypertension, and erectile dysfunction. Alpha1-selective adrenergic receptor (a1-AR) antagonists (eg, alfuzosin, doxazosin, tamsulosin, terazosin) remain the cornerstone of therapy for LUTS/BPH. In addition, 5-alpha-reductase inhibitors (ie, dutasteride, finasteride) have been associated with improvements in LUTS/BPH in men with larger prostates, especially when used in combination with a1-AR antagonists. Although all these drugs have been shown to be beneficial for the treatment of BPH, there are differences in side-effect profiles. When selecting an appropriate course of therapy, these side effects and any impact they may have on existing comorbid conditions must be considered.
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                Author and article information

                Contributors
                Hsi‐Chin Wu:
                ORCID: https://orcid.org/0000-0001-7409-3295
                wuhc@mail.cmuh.org.tw
                Journal
                Journal ID (nlm-ta): Cancer Med
                Journal ID (iso-abbrev): Cancer Med
                Journal ID (doi): 10.1002/(ISSN)2045-7634
                Journal ID (publisher-id): CAM4
                Title: Cancer Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2045-7634
                Publication date (Electronic): 09 April 2019
                Publication date Collection: May 2019
                Volume: 8
                Issue: 5 ( doiID: 10.1002/cam4.2019.8.issue-5 )
                Pages: 2514-2523
                Affiliations
                [ 1 ] Department of Traditional Chinese Medicine Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
                [ 2 ] Department of Applied Cosmetology National Tainan Junior College of Nursing Tainan Taiwan
                [ 3 ] Department of Health Services Administration China Medical University Taichung Taiwan
                [ 4 ] Department of Urology China Medical University Hospital, China Medical University Taichung Taiwan
                [ 5 ] Department of Family Medicine Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
                Author notes
                [*] [* ] Correspondence

                Hsi‐Chin Wu, Department of Urology, China Medical University Hospital, China Medical University, Taichung, Taiwan.

                Email: wuhc@ 123456mail.cmuh.org.tw

                Author information
                https://orcid.org/0000-0001-7409-3295
                Article
                Publisher ID: CAM42025
                DOI: 10.1002/cam4.2025
                PMC ID: 6536940
                PubMed ID: 30968600
                SO-VID: c2ba9b15-c3d8-4d09-a969-36ce2af04a76
                Copyright © © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 September 2018
                Date revision received : 21 January 2019
                Date accepted : 25 January 2019
                Page count
                Figures: 2, Tables: 3, Pages: 10, Words: 6145
                Funding
                Funded by: NRPB Stroke Clinical Trial Consortium
                Award ID: MOST 105-2325-B-039-003
                Funded by: Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence
                Award ID: MOHW107-TDU-B-212-123004
                Funded by: Academia Sinica Taiwan Biobank Stroke Biosignature Project
                Award ID: BM10501010037
                Categories
                Subject: Original Research
                Subject: Cancer Prevention
                Subject: Original Research
                Custom metadata
                source-schema-version-number 2.0
                component-id cam42025
                cover-date May 2019
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.3 mode:remove_FC converted:28.05.2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: benign prostate hyperplasia,diabetes,metformin,prostate cancer,traditional chinese medicine
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: benign prostate hyperplasia, diabetes, metformin, prostate cancer, traditional chinese medicine

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