Research Center of Environmental Trace Toxic Substance, National Cheng Kung University, Tainan, Taiwan.
Department of Urology, National Cheng Kung University Hospital, Tainan, Taiwan.
Environ Int. 2019 May;126:184-192. doi: 10.1016/j.envint.2019.02.006. Epub 2019 Feb 22.
Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (p < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (p < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.
前列腺增生可能影响多达 30%的男性，并且可能导致老年人下尿路出现症状和体征。雌雄激素分泌失衡在前列腺的病理生理学中起着重要作用。邻苯二甲酸酯——环境内分泌干扰物——会影响雄激素的分泌并扰乱包括睾丸和前列腺在内的性器官，但潜在机制尚不清楚。我们根据欧洲泌尿外科学会 (EAU) 指南，于 2015 年至 2017 年在台湾南部的泌尿科诊所招募了 207 名被诊断为良性前列腺增生 (BPH) 和前列腺增大的老年男性。我们在同一天为所有患者采集了血液和尿液样本。我们使用多元线性回归、关联和潜在相互作用，对氧化应激 (OS) 标志物、甾体激素和 11 种尿邻苯二甲酸酯代谢物进行了测量和分析，然后对混杂因素进行了调整。邻苯二甲酸二 (2-乙基己基) 酯 (DEHP) 代谢物水平，特别是单-(2-乙基己基)邻苯二甲酸酯，与雄激素、雌激素、激素比值、诱导型一氧化氮合酶 (iNOS)、8-羟基-2'-脱氧鸟苷 (8-OHdG)、前列腺特异性抗原 (PSA) 和前列腺体积 (PV) 呈正相关 (p<0.05)。PV 和 PSA 与雄激素、雌激素、激素比值和 OS 标志物呈正相关 (p<0.05)。由雄激素、雌激素和 OS 标志物介导的 DEHP 对前列腺增大的暴露估计百分比范围为 3.5%至 63.1%。DEHP 通过增加二氢睾酮 (DHT)、雌二醇 (E)、转化酶芳香酶和 5α 还原酶以及活性氧 (8-OHdG 和 iNOS) 的产生，促进了 BPH 的进展。在患者接触邻苯二甲酸酯后，性激素和 OS 可能是重要的增生促进剂，尤其是 DEHP。
