{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:21:00Z","timestamp":1790198460349,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A prospective, self-controlled study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixty patients diagnosed with PCOS and IR underwent three months of comprehensive therapy, including lifestyle modification, oral metformin (1000\u20131500 mg\/day), and a COC (3 mg drospirenone and 20 \u00b5g 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\n                      <jats:italic>PON1<\/jats:italic>\n                      Q192R and C-108T genetic polymorphisms, oxidative stress markers, hormonal profiles, and metabolic parameters, were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). In contrast, serum PON1 lactonase activity, apolipoprotein (apo)A1, triglycerides, and 2-h glucose levels were significantly increased (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Spearman\u2019s 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 (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.chictr.org.cn\/showproj.html?proj=152682<\/jats:ext-link>\n                      , identifier ChiCTR2200057114.\n                    <\/jats:p>\n                  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