Efficacy of treatments for polycystic ovarian syndrome management in adolescents: a systematic review and network meta-analysis

Limited evidence on treatment options for polycystic ovarian syndrome (PCOS) has led to considerable variation in healthcare practices. We aimed to compare the effects of metformin and/or oral contraceptive pills (OCPs) in combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions among adolescents aged 11-19 years with PCOS. Literature searches were performed in Medline, Embase, and the Cochrane Central Register of Controlled Trials from database inception through December 2018, with no language restriction. Two reviewers screened titles and abstracts, assessed full text eligibility, and extracted information from eligible trials. Evidence was synthesized through network meta-analyses (NMA) using Bayesian random-effects approach. We identified 37 RCTs, in which 2400 patients were randomized. NMA showed no statistically important difference among all interventions to improve menstrual regulation, or body mass index. Moderate quality evidence showed hirsutism scores were reduced by multiple interventions that included single and combination medications namely; lifestyle intervention, metformin, OCP, spironolactone, pioglitazone, metformin-OCP, metformin-spironolactone, metformin-flutamide, against placebo. Moderate quality evidence showed OCP results in more dysglycaemia compared to metformin (odds ratio 2.98; 95%credible interval 1.02, 8.96), no intervention resulted in dysglycaemia reduction. In conclusion, metformin and OCP as monotherapy or in combination with other interventions compared to placebo can reduce hirsutism scores, but none of these medications lead to effective menstrual cycle regulation or weight reduction. However, the use of OCP leads to worse cardiometabolic risk factors. Further research into new treatment options is urgently needed.