The comparative effectiveness of 55 interventions in obese patients with polycystic ovary syndrome: A network meta-analysis of 101 randomized trials

Abstract

Background Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-age females. The prevalence of obesity in PCOS patients reaches up to 80%, which is 2-fold higher than the general population. Objective The present study aimed to compare the effectiveness of 55 pharmacological interventions across 17 different outcomes in overweight/obese PCOS patients with hyperandrogenism manifestations for both short- and long-term follow-ups. A comprehensive literature search was performed on PubMed, Scopus, Embase, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled trials comparing any conventional pharmacological intervention as a monotherapy or a combination in overweight/obese patients with polycystic ovary syndrome and hyperandrogenism manifestations. Extracted data included three main parameters; I. Anthropometric parameters (BMI, Waist and Hip circumferences, and Waist/HIP ratio), II. Hormonal parameters (FSH, LH, FSG, SHBG, Estradiol, Total Testosterone, Free testosterone, DHEAS, Androstenedione), and III. Metabolic parameters (Total Cholesterol, LDL-C, HDL-C, Triglycerides, Fasting glucose, Fasting glucose, HOMA-IR). Critical appraisal and risk of bias assessments were performed using the modified Jadad scale, and the overall quality of this network meta-analysis was evaluated according to the CINeMA framework. We performed both a pairwise meta-analysis and a network meta-analysis to evaluate the effect sizes with 95% CI, and we calculated the surface under the cumulative ranking curve (SUCRA) for each intervention. Results Our final search on May 15th 2021 retrieved 23,305 unique citations from searching six electronic databases. Eventually, 101 RCTs of 108 reports with a total of 8,765 patients were included in our systematic review and multi-treatments meta-analysis. 55 different interventions were included: 22 monotherapies, and 33 combinations. The two-dimensional cluster ranking of the average SUCRA values for metabolic and hormonal parameters with significant estimates revealed flutamide (77.5%, 70%; respectively) as the highest and rosiglitazone (38.2%, 26.3%; respectively) as the lowest, in terms of the overall efficacy in reducing weight and hyperandrogenism. However, cyproterone-acetate+ethinylestradiol exhibited a higher ranking in improving hormonal parameters (71.1%), but even a lower-ranking regarding metabolic parameters (34.5%). Conclusions and relevance Current evidence demonstrated the superiority of flutamide in improving both metabolic and hormonal parameters, and the higher efficacy of cyproterone-acetate+ethinylestradiol only in improving hormonal parameters. Nearly all interventions were comparable in female hormones, FGS, HDL, glucose, and insulin levels improvements.

Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction

“…In order to tackle excess androgen production in PCOS, patient are sometimes prescribed flutamide, an androgen receptor inhibitor. Interestingly, flutamide not only can lower testosterone action in target tissues but may also help improve the cardiometabolic alterations (76) and features of adipose tissue dysfunction (77) observed in PCOS. Our study was not designed to compare PCOS to non-PCOS women with severe obesity.…”

Increased Adipose Tissue Indices of Androgen Catabolism and Aromatization in Women With Metabolic Dysfunction

“…In order to tackle excess androgen production in PCOS, patients are sometimes prescribed flutamide, an androgen receptor inhibitor. Interestingly, flutamide not only can lower testosterone action in target tissues but may also help improve the cardiometabolic alterations ( 77 ) and features of adipose tissue dysfunction ( 78 ) observed in PCOS. Our study was not designed to compare PCOS to non-PCOS women with severe obesity.…”

Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS

“…Although PCOS and its associated complications are complex polygenic and multifactorial conditions, it is generally considered as a disorder of hormonal dysfunction or fertility challenge. A recent meta-analysis of 101 randomized controlled trials investigated 55 drug interventions and reported comparable effect on various reproductive, metabolic, and hormonal parameters in obese/overweight PCOS women [ 38 ]. This shows that although there might be diverse clinical presentation of this syndrome, ultimately there must be major common pathway that amplifies the effects from various initial sources and leads to overall progression of PCOS.…”