Work

Effects of combined oral contraceptives and metformin on paraoxonase 1 lactonase activity and status in patients with polycystic ovary syndrome and insulin resistance

Year: 2026

Type: article

Abstract: Objective To investigate the effects of combined oral contraceptives (COCs) and metformin treatment on the lactonase activity and status of paraoxonase 1 (PON1), and oxidative stress levels in patients with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Design A prospective, self-controlled study. Methods Sixty patients diagnosed with PCOS and IR underwent three months of comprehensive therapy, including lifestyle modification, oral metformin (1000–1500 mg/day), and a COC (3 mg drospirenone and 20 µg ethinyl estradiol). Clinical data and blood samples were collected at baseline and after three months of treatment. PON1 levels, lactonase activity, and normalized lactonase activity (NLA), along with PON1 Q192R and C-108T genetic polymorphisms, oxidative stress markers, hormonal profiles, and metabolic parameters, were analyzed. Results After treatment, significant decreases were observed in body mass index (BMI), Global Acne Grading System scores, androstenedione, fasting insulin, the homeostasis model assessment of insulin resistance index, and total antioxidant capacity ( P < 0.05). In contrast, serum PON1 lactonase activity, apolipoprotein (apo)A1, triglycerides, and 2-h glucose levels were significantly increased ( P < 0.05). Spearman’s correlation analysis showed that lactonase activity and PON1 status were correlated with serum apoA1, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total oxidant status, and the oxidative stress index ( P < 0.05). Moreover, the group with improved NLA showed higher PON1 lactonase activity and HDL-C levels, whereas the group without improved NLA showed higher PON1 levels after treatment. Conclusion Treatment with COCs and metformin enhanced the antioxidant capacity of circulating HDL and improved BMI, glycolipid metabolism, IR, and hyperandrogenism in patients with PCOS and IR. Clinical Trial Registration https://www.chictr.org.cn/showproj.html?proj=152682 , identifier ChiCTR2200057114.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2025.1725822