The mediating effect of serum total testosterone in the association between the ZJU index and PCOS

The ZJU index is an innovative computational method that integrates triglycerides (TG), body mass index (BMI), fasting blood glucose (FBG), and the alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio. Previous studies indicated that it is strongly associated with markers of lipid metabolism and glucose intolerance. However, no studies have yet explored the association between the ZJU index and the chances of getting PCOS. Therefore, a total of 1352 female participants (1169 controls and 183 PCOS patients) who underwent in vitro fertilization and embryo transfer (IVF-ET) were included in the study. Basic demographic information and laboratory biochemical indicators of the participants were collected, and the ZJU index was calculated. Multivariate logistic regression model was employed to examine the association between the ZJU index and the chances of getting PCOS, with the ZJU index analyzed both as a categorical variable (quartiles) and as a continuous variable. Multivariate linear regression model was used to explore the association between the ZJU index and baseline serum sex hormone levels, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, estradiol (E2), progesterone (P), prolactin (PRL), and total testosterone (TT). The restricted cubic spline (RCS) regression model was used to examine both linear and nonlinear associations between the ZJU index and the chances of getting PCOS. A mediation analysis model was used to explore whether TT is a possible intermediary factor in the association between the ZJU index and the chances of getting PCOS. The results were presented as odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) for logistic regression and as β coefficients with 95% CIs for linear regression. The ability of the ZJU index, BMI, and HOMA-IR to identify PCOS was assessed using receiver operating characteristic (ROC) analysis and the area under the curve (AUC), with comparisons of the AUCs performed using the Delong test. According to the multivariate logistic regression analysis, the ZJU index, when analyzed as a continuous variable, was positively associated with the chances of getting PCOS (OR = 1.09, 95% CI: 1.05-1.14, P < 0.001). When the ZJU index was categorized into quartiles, and Q1 (24.19-31.67; mean ± SD: 29.77 ± 1.36) was used as the reference, the chances of getting PCOS were 1.69 (95% CI: 0.90-3.17) in Q2 (31.68-34.58), 1.91 (95% CI: 1.01-3.60) in Q3 (34.59-38.51), and 4.44 (95% CI: 2.27-8.66) in Q4 (38.52-54.77), suggesting a dose-dependent increase, especially above 34.59. Multivariate linear regression analysis showed that the ZJU index was positively associated with TT (β = 0.01, 95% CI: 0.00-0.02, P < 0.001), while it was negatively associated with FSH (β = -0.06, 95% CI: -0.10 - -0.01, P = 0.008). There were no significant associations between the ZJU index LH/FSH (β = 0.00, 95% CI: -0.01- 0.01, P = 0.656). RCS regression model demonstrated a significant linear and positive association between the ZJU index and PCOS. Serum TT levels may partially account for the positive association between the ZJU index and the chances of getting PCOS, with an estimated 10.00% of this association that may be explained through an indirect pathway involving TT. ROC analysis showed that ZJU index (AUC = 0.637) was a stronger predictor of PCOS than BMI (AUC = 0.625) and HOMA-IR (AUC = 0.621). The ZJU index was significantly associated with increased chances of having PCOS in infertile women undergoing IVF-ET. Additionally, our findings suggest that TT may be a possible intermediary factor in the association between the ZJU index and the chances of getting PCOS. This suggests that metabolic dysfunction, particularly insulin resistance, may contribute to the chances of getting PCOS through hyperandrogenism rather than by disrupting hypothalamic-pituitary regulation.