Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation

Objective: Evidence suggests that increased gut permeability may be associated with polycystic ovary syndrome (PCOS). Human zonulin is currently the only physiological mediator known to reversibly regulate gut permeability by disassembling intestinal tight junctions. So far, no data on serum zonulin levels in patients with PCOS are available. This study aimed to determine circulating serum zonulin levels in women with PCOS and discuss the relationship between zonulin, insulin resistance, and menstrual disorders in this group. Design: A case-control study. Methods: The study includes 78 women recently diagnosed with PCOS and 63 age-matched healthy controls recruited. Serum zonulin levels were determined by ELISA. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda and DeFronzo's insulin sensitivity index (ISI). Results: PCOS women had higher serum zonulin levels (P=0.022). After adjustment for age and BMI, zonulin levels significantly correlated with HOMA-IR and ISI. Furthermore, PCOS women with more severe menstrual disorders had significantly higher zonulin levels and displayed an inverse correlation between zonulin and the number of menstrual cycles per year (r= -0.398, P < 0.001). Conclusions: Serum zonulin, a biomarker for gut permeability, is increased in PCOS women and correlates with insulin resistance and severity of menstrual disorders. It suggests that alterations in gut permeability may play a role in the pathophysiology of PCOS, and serum zonulin might be used as a biomarker for both risk stratification and therapeutic outcomes in PCOS women.