PurposeTo confirm if the CYP17A1 gene regulates the ratio of T/E leading to MetS-BPH.Methods824 men, aged 47–88 years, were recruited into this study through consecutive routine physical examination programs and long-term outpatient screening. Several parameters, including SNPs of CYP17A1 gene, total testosterone, estradiol, and the ratio of total testosterone to estradiol (T/E) were obtained for each participant. Based on the diagnosis of BPH, MetS, and MetS-BPH, the participants were divided into BPH and non-BPH groups, MetS and non-MetS groups, and MetS-BPH and non-MetS-BPH groups. Values of the obtained parameters were evaluated using one-way analysis of variance, Student’s t-test, Chi-squared test, and logistic regression analysis.ResultsSNPs of the CYP17A1 gene, including the rs743572 genotypes (GG, GA, and AA), rs3781287 genotypes (GG, GT, TT), and rs4919686 genotypes (CC, CA, and AA), were present in every group. Only the GG genotype of rs743572 was independently associated with BPH (OR = 5.868, 95% CI: 3.363–7.974, P < 0.001), MetS (OR = 7.228, 95% CI: 3.925–11.331, P < 0.001), and MetS-BPH (OR = 3.417, 95% CI: 1.783–5.266, P < 0.001) after adjusting for age. In the population of genotype GG of rs743572, the decrease in T/E ratio was an independent risk factor for BPH (OR = 839.756, 95% CI: 36.978-1334.263, P = 0.001), MetS (OR = 376.988, 95% CI: 12.980-488.976, P < 0.003), and MetS-BPH (OR = 388.236, 95% CI: 24.869-495.363, P = 0.003).ConclusionThe GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH populations.Trial registration numberChiCTR2200057632 “retrospectively registered”.Date of registrationMarch 15, 2022 “retrospectively registered”.