Discussion
PCOS, metabolic disorders, abdominal obesity, overweight, metabolic disturbance, hyperinsulinemia
IRREGULAR MENSTRUAL CYCLE, DISORDERS, METABOLIC DISORDERS, ADVERSE EFFECTS, METABOLIC DISTURBANCE, HYPERINSULINEMIA, OXIDATIVE STRESS, INSULIN SENSITIVITY
In this randomized controlled trial, our results demonstrate that both treatments are effective in recovering ovary morphology and promoting regular menstruation. We show that GLP-1RA + Met treatment is superior to CPA/EE + Met treatment in reducing weight and improving glycolipid metabolism in overweight/obese women with PCOS. Metformin greatly contributed to the common improvements in the clinical effect of both treatments, although some monotherapy studies of metformin failed to find many clinical benefits [GLP-1RA + Met is more effective in reducing weight, improving glucolipid metabolism, insulin sensitivity, and liver function. The combination therapy shows a synergistic effect. In this study, after the 12-week treatment, patients in the CPA/EE + Met group lost an average of 1.8 kg compared to 7.4 kg in the GLP-1RA + Met group. GLP-1RA + Met is also superior to CPA/EE + Met in reducing waist circumference; therefore, it may provide better control of abdominal obesity. Consistent with our result, Rui-Lin Ma et al. [Surprisingly, GLP-1RA + Met treatment resulted in the increased occurrence of dominant follicles without androgen decrease, which might result from improved hyperinsulinemia and then restore the regular menstrual cycle and promote the formation of dominant follicles [Thus, considering the long-term benefits of improving metabolism and the urgency of pregnancy, GLP-1RA + Met is more effective than CPA/EE + Met in promoting ovulation and improving metabolic disturbance for overweight women with PCOS. Moreover, these beneficial effects also suggested the possibility of reducing the occurrence of metabolic and reproductive endocrinology disorders in PCOS patients and their future generations.Previous studies have shown that the abundance of some plasma proteins changed significantly in PCOS patients, which contributes to the pathophysiological mechanism [Although a direct causal relationship could not be determined in our study, there was a correlation between the changes in plasma protein levels caused by drug intervention and the improvement of clinical symptoms. In detail, oxidative stress injury and excessive self-protection have been proven to be involved in the occurrence and development of metabolic disorders and PCOS [In addition to the proteomics analysis that provides new molecular insights, another major strength of the current study is the comprehensive phenotypic characterization across a timeline. Limitations of this trial include a relatively small sample size and single-center design. Additionally, lifestyle changes were not controlled for as we aimed to isolate the effects of the drug on overweight patients with PCOS. Given the special administration method (I.H.) with a GLP-1RA, participants and investigators were not blinded to the treatment in this trial. Future studies can test newer GLP-1RAs associated with a lower incidence of gastrointestinal side effects, and the prospective studies should be designed to verify the specific role of plasma candidate biomarkers we found in the treatment of PCOS. The adverse effects of GLP-1RA+Met were mainly observed in the gastrointestinal system, which might be related to its action in the autonomic nervous system [