Tseng Chin-Hsiao
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Front Pharmacol. 2022 Jul 22;13:799290. doi: 10.3389/fphar.2022.799290. eCollection 2022.
To investigate the risk of varicocele, erectile dysfunction (ED), infertility, prostatitis, benign prostate hyperplasia (BPH) and prostate cancer associated with metformin use. A total of 261,838 males, mean age 52.39 years (SD: 11.39), with a new-onset type 2 diabetes mellitus in 1999-2009 were identified from Taiwan's National Health Insurance. Among them, 175,171 were metformin initiators [metformin (+)] and 86,667 were non-metformin initiators [metformin (-)] in the initial 12-month prescriptions of antidiabetic drugs. Follow-up started after the initial 12-month prescriptions. Outcomes were followed up until 31 December 2011. Intention-to-treat (ITT) and per-protocol (PP) hazard ratios comparing metformin (+) to metformin (-) were estimated by Cox regression incorporated with the inverse probability of treatment-weighting using propensity scores. The median follow-up time ranged 5.55-6.82 years in metformin (-) and 4.36-5.17 years in metformin (+) for different outcomes in ITT analyses. The respective median follow-up time in PP analyses ranged 2.20-2.61 years in metformin (-) and ranged 3.99-4.65 years in metformin (+). In the ITT analyses, for metformin (-), the incidence rates (per 100,000 person-years) of varicocele, ED, infertility, prostatitis, BPH and prostate cancer were 26.42, 455.89, 22.82, 590.23, 4226.19, and 141.69, respectively; and the respective incidence rates for metformin (+) were 25.65, 488.10, 32.60, 510.30, 3685.66, and 116.57. The hazard ratios (95% confidence intervals) comparing metformin (+) to metformin (-) in the ITT analyses were 0.960 (0.784-1.174) for varicocele, 1.077 (1.026-1.130) for ED, 1.368 (1.116-1.676) for infertility, 0.887 (0.849-0.927) for prostatitis, 0.883 (0.868-0.899) for BPH and 0.878 (0.802-0.961) for prostate cancer. The hazard ratios for the respective outcomes in the PP analyses were 0.845 (0.662-1.078), 1.350 (1.264-1.441), 1.396 (1.078-1.808), 0.800 (0.756-0.846), 0.875 (0.855-0.895), and 0.613 (0.548-0.686). Metformin use in patients with type 2 diabetes mellitus is associated with a neutral effect on varicocele, a higher risk of sexual dysfunction (ED and infertility) and a reduced risk of prostate-related health (prostatitis, BPH and prostate cancer).
为调查使用二甲双胍与精索静脉曲张、勃起功能障碍（ED）、不育症、前列腺炎、良性前列腺增生（BPH）及前列腺癌的风险。从台湾全民健康保险中识别出1999年至2009年新诊断为2型糖尿病的261,838名男性，平均年龄52.39岁（标准差：11.39）。其中，在最初12个月的抗糖尿病药物处方中，175,171人为二甲双胍起始使用者[二甲双胍（+）]，86,667人为非二甲双胍起始使用者[二甲双胍（-）]。随访在最初12个月处方后开始。随访至2011年12月31日。通过Cox回归结合使用倾向得分的逆概率治疗加权法，估计二甲双胍（+）与二甲双胍（-）相比的意向性治疗（ITT）和符合方案（PP）风险比。在ITT分析中，不同结局下二甲双胍（-）的中位随访时间为5.55 - 6.82年，二甲双胍（+）为4.36 - 5.17年。PP分析中，二甲双胍（-）的相应中位随访时间为2.20 - 2.61年，二甲双胍（+）为3.99 - 4.65年。在ITT分析中，对于二甲双胍（-），精索静脉曲张、ED、不育症、前列腺炎、BPH和前列腺癌的发病率（每10万人年）分别为26.42、455.89、22.82、590.23、4226.19和141.69；二甲双胍（+）的相应发病率分别为25.65、488.10、32.60、510.30、3685.66和116.57。ITT分析中，二甲双胍（+）与二甲双胍（-）相比的风险比（95%置信区间），精索静脉曲张为0.960（0.784 - 1.174），ED为1.077（1.026 - 1.130），不育症为1.368（1.116 - 1.676），前列腺炎为0.887（0.849 - 0.927），BPH为0.883（0.868 - 0.899），前列腺癌为0.878（0.802 - 0.961）。PP分析中各结局的风险比分别为0.845（0.662 - 1.078）、1.350（1.264 - 1.441）、1.396（1.078 - 1.808）、0.800（0.756 - 0.846）、0.875（0.855 - 0.895）和0.613（0.548 - 0.686）。2型糖尿病患者使用二甲双胍对精索静脉曲张有中性影响，对性功能障碍（ED和不育症）有较高风险，对前列腺相关健康问题（前列腺炎、BPH和前列腺癌）有降低风险的作用。
