Relationship between proinflammatory cytokines and clomiphene resistance in patients with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. We aimed to investigate the correlations between proinflammatory cytokine levels and clomiphene resistance in patients with PCOS. Methods: Between January 2019 and January 2020, a total of 72 PCOS patients who attended our department were administered clomiphene 50-100 mg/day on days 5-9 of the menstrual cycle to induce ovulation. Patients were divided into a clomiphene-sensitive group (n=42) and a clomiphene-resistant group (n=30). The proinflammatory cytokines interleukin-23 (IL-23), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor a (TNF-alpha), angiopoietin-2, and adiponectin were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver-operating characteristic curve was employed to determine the capability of various parameters to distinguish clomiphene resistance. The univariate logistic regression analysis was used to analyze the associations between pro-inflammatory cytokine levels and clomiphene resistance in PCOS. Results: Serum IL-23 levels showed no statistically significant difference between the clomiphene-sensitive and the clomiphene-resistant groups, whereas MCP-1, TNF-alpha, angiopoietin-2, and adiponectin levels were significantly different between the two groups (all P<0.05). Univariate logistic regression analysis indicated that elevated serum TNF-alpha [odds ratio (OR) =1.88, P<0.001], decreased angiopoietin-2 (OR =0.61, P=0.007), and adiponectin (OR =0.39, P=0.012) levels were significantly associated with clomiphene resistance. The sensitivity of TNF-alpha and angiopoietin-2 to distinguish clomiphene resistance in patients with PCOS was 100%. Moreover, the diagnostic efficiency of TNF-alpha and adiponectin in identifying clomiphene resistance was significantly higher than that of MCP-1 and angiopoietin-2 (all P<0.05). Conclusions: Abnormal TNF-alpha, angiopoietin- 2, and adiponectin levels may be associated with clomiphene resistance in PCOS patients. The serum proinflammatory cytokines TNF-alpha and adiponectin are helpful discriminators of clomiphene resistance in PCOS patients.