The Impact of Soy Products and Isoflavones on Male Reproductive Hormones: A Systematic Review and Dose–Response Meta‐Analysis of Randomized Controlled Trials

ABSTRACT Given the growing evidence that soy may exhibit estrogenic effects in males under certain conditions, it was essential to conduct a comprehensive study to elucidate this. This dose–response meta‐analysis of randomized controlled trials was conducted to investigate the effects of soy and its products on male sex hormones. We systematically searched multiple databases up to September 2024. Overall estimates were calculated using the DerSimonian and Laird random‐effects model. Between‐study heterogeneity was assessed using the Cochrane Q test and the I ‐squared statistic. A one‐stage dose–response meta‐analysis was conducted utilizing restricted maximum likelihood estimation, taking into account the dosage of soy isoflavones. The risk of bias assessment and the certainty of evidence were evaluated using the cochrane risk of bias version 2.0 tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, respectively. A nonlinear dose–response relationship was observed between soy isoflavones and levels of estradiol and sex hormone‐binding globulin (SHBG). Estradiol levels increased by ∼6.5 pg/mL when the soy isoflavone dosage was 72.2 mg/day higher than the reference dose (0 mg/day). Additionally, SHBG levels rose to ∼9 nmol/L when the soy isoflavone dosage was 120 mg/day above the reference dose ( p ‐nonlinearity < 0.001 for both). Subgroup analysis suggested that the study design, duration, and the use of adjuvant interventions alongside exercise may contribute to the heterogeneity observed in estradiol analyses. A nonlinear dose–response relationship was observed between soy and levels of estradiol and SHBG. The limited number of studies included may restrict the generalizability of our findings.