P-632 Hormonal imbalance in umbilical cord blood: a propensity score-matched analysis of endometriosis, PCOS, and healthy controls

Abstract Study question Do umbilical vein cord blood hormonal levels differ among pregnant women with endometriosis, polycystic ovarian syndrome (PCOS), and healthy controls delivering singleton female infants? Summary answer Umbilical cord blood levels of estradiol, the estradiol-to-testosterone ratio, and 11-deoxycortisol are significantly higher in women with endometriosis compared to healthy controls. What is known already Endometriosis and PCOS affect approximately 1 in 10 women of reproductive age. Both conditions exhibit hormonal imbalances, primarily through paracrine production. Evolutionary theories suggest an inverse relationship between endometriosis and PCOS, framing them as diametrical diseases. However, during pregnancy, they exhibit similar and overlapping comorbidities, likely including altered placental function. Umbilical vein cord blood hormonal levels, a potential indicator of placental-fetal interaction, remain understudied in both conditions. This study delves into umbilical vein cord blood hormonal differences among women with endometriosis, PCOS, and healthy controls, aiming to unveil their potential influence on placental function and fetal development. Study design, size, duration This is a nested case-control study with propensity score matching of women with endometriosis, PCOS, and controls (1:1:3 ratio). Endometriosis was defined by surgery or imaging. PCOS was defined according to the Rotterdam Criteria based on anovulation and ultrasound findings. Controls had no reported diseases and a history of regular menstrual cycles. Propensity scores were calculated using logistic regression based on age, mode of delivery and gestational age, implementing nearest neighbor matching to minimize confounding. Participants/materials, setting, methods Umbilical cord blood was collected from pregnant women at the time of delivery of singleton female infants. Hormonal levels were quantified using Liquid Chromatography-Mass Spectrometry. Maternal comorbidities, pregnancy outcomes, and neonatal parameters were collected. Weight/Length Ratio (WLR) centiles were calculated based on the Intergrowth-21st standards. Between-group differences were analyzed using ANOVA or Kruskal-Wallis tests with Bonferroni correction for multiple comparisons. Correlations between cord blood hormone levels and neonatal growth metrics were assessed using Spearman’s rho. Main results and the role of chance A total of 85 women were included: 17 with endometriosis, 17 with PCOS, and 51 controls. There were no significant differences between groups in maternal age (p = 0.96), mode of delivery (p = 0.69), or gestational age at delivery (p = 0.50). Pregnancy complications were similar in women with endometriosis (35.3%), PCOS (23.5%) and controls (17.6%) (p = 0.31). Weight gain during pregnancy was also similar across groups (p = 0.51). Neonatal outcomes were comparable, with median newborn WLR centiles being 44.39 [35.71–51.77] in endometriosis, 42.08 [30.84–63.93] in PCOS, and 41.22 [32.21–75.19] in controls (p = 0.88). Hormonal analyses of umbilical vein cord blood revealed significantly higher estradiol levels in endometriosis compared to controls (6.8 [4.28–9.07] vs. 2.41 [1.14–6.6] mcg/L; p = 0.002; Bonferroni-adjusted p = 0.006), higher 11-deoxycortisol levels (9.41 [7.27–13.47] vs. 5.47 [3.69–8.89] mcg/L; p = 0.002; Bonferroni-adjusted p = 0.006), and a higher estradiol-to-testosterone ratio (171.7 [120.7–209.87] vs. 39.16 [19.66–80.33]; p = 0.003; Bonferroni-adjusted p = 0.009). Women with endometriosis were significantly more likely to have estradiol-to-testosterone ratios above the cohort median (82.4% vs. 33.3% in controls; p < 0.001). No significant differences were observed between PCOS and controls. In women with endometriosis, but not in those with PCOS or controls, 11-deoxycortisol levels correlated strongly with newborn weight (r = 0.88; p = 0.002) and WLR (r = 0.87; p = 0.002). Limitations, reasons for caution The small sample size limits the generalizability of findings. PCOS diagnosis relied on ultrasound and anovulatory cycles, without routine evaluation of hyperandrogenism, which likely affect comparisons. Further studies with larger cohorts and longitudinal designs are necessary to validate these findings and clarify potential endocrine and paracrine effects. Wider implications of the findings This is the first study analyzing hormonal levels in umbilical vein cord blood of women with endometriosis. In utero exposure to elevated hormone levels, particularly estradiol, suggests novel pathogenic pathways and may influence placental-fetal interactions, potentially affecting long-term outcomes in the offspring of women with endometriosis. Trial registration number No