Publication Date
1-1-2024
Journal
Endocrine
DOI
10.1007/s12020-023-03487-4
PMID
37653215
PMCID
PMC10806039
PubMedCentral® Posted Date
8-31-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Female, Humans, Metformin, Polycystic Ovary Syndrome, Cyproterone Acetate, Ethinyl Estradiol, Overweight, Prospective Studies, Proteomics, Luteinizing Hormone, Insulin Resistance, Biomarkers, Glutathione Transferase, PCOS (Polycystic Ovary Syndrome), Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA), Metformin, Proteomics Analysis
Abstract
PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.
METHODS: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA.
RESULTS: Eighty(80%) patients completed the study. Both interventions improved menstrual cycle, polycystic ovaries, LH(luteinizing hormone) and HbA1c(hemoglobin A1c) levels after the 12-week treatment. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI (Body Mass Index), and waist circumference, FBG(fasting blood glucose), AUCI(area under curve of insulin),TC (Total Cholesterol), IL-6(Interleukin-6) and improving insulin sensitivity, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in improving hyperandrogenemia, including T(total testosterone), LH, LH/FSH(Luteinizing hormone/follicle-stimulating hormone), SHBG(sex hormone-binding globulin) and FAI (free androgen index). By contract, GLP-1RA+Met group only improved LH. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9).
CONCLUSIONS: Both CPA/EE+Met and GLP-1RA + Met treatment improved reproductive functions in overweight PCOS women. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI, and waist, and improving metabolism, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in reducing hyperandrogenemia. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment.
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Endocrinology, Diabetes, and Metabolism Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons
Comments
NCT03151005. Registered 12 May, 2017, https://clinicaltrials.gov/ct2/show/NCT03151005.
Associated Data