PMON208 METFORMIN, SPIRONOLACTONE AND ORAL CONTRACEPTIVES IN POLYCYSTIC OVARY SYNDROME: A NETWORK META-ANALYSIS
Authors: Rodriguez-Gutierrez Rene , Raygoza-Cortez Karina , Leal Mariana García , de León Gutierrez Humberto , Peña Tomãs Alvarado , Flores Melissa Sãenz , Santos Yeudiel Suro , Rodríguez Omar Fernando Rodríguez , Fuentes Stephie Oyervides , Bautista Mario Rodriguez , Fernãndez Javier Obeso , Rodriguez Andrea Flores , Colmenero Fernando Díaz Gonzãlez , Gonzãlez-Gonzãlez José Gerardo 
Published: November 2022

Abstract

Background
Polycystic ovary syndrome (PCOS) is a complex endocrine disease with awide-spectrum of clinical presentations. For this reason, several therapeutic interventions have been proposed. Metformin, spironolactone and oral contraceptives (OC), alone or in combination, have demonstrated benefit, however, their results are heterogeneous across the evidence. Although several meta-analyses have evaluated these interventions, none has studied the combination between them nor focused on patient-important outcomes.

Objective
The primary aim of this study was to assess the effect of metformin, spironolactone and OC on testosterone levels. Other outcomes of interest were body mass index (BMI), metabolic profile (glucose, insulin, triglycerides and cholesterol), hormonal measures (LH, FSH, SHBG), and patient-important outcomes comprising hirsutism (measured with the Ferriman-Gallwey score), emotional well-being and quality of life.

Methods
A comprehensive search was conducted in MEDLINE, EMBASE, Web of Science, and Scopus from database inception to November 2021. Randomized clinical trials (RCTs) with at least two intervention arms with either OC, metformin, spironolactone, placebo or any combination of these agents for a minimum of 12 weeks were included. No language or date restrictions were applied. We performed a frequentist random effects network meta-analysis to estimate mean differences (MDs) and standardized mean differences (SMDs) alongside 95% confidence intervals (CIs). PROSPERO: CRD42022299547 Results: A total of 101 trials (including 6,837 women) met the inclusion criteria. Overall, the combination of the pharmacological agents (OC + Spironolactone, Metformin + OC and Metformin + Spironolactone) produced the greatest reductions in testosterone levels compared to monotherapy and placebo. Spironolactone added to OC was the highest ranked treatment (MDs ranging from -0.66 [95% CI -1.30;-0.03] with OCP to -1.08 [95% CI -1.70;-0.46] compared with Metformin). All pharmacological treatments were superior to placebo on this outcome. On anthropometric measures, Metformin, Metformin + OC and Placebo were superior to OC and spironolactone alone at reducing BMI. On metabolic outcomes, the combination of Metformin + Spironolactone and Metformin alone showed to be superior at reducing glucose levels when compared to OC and Metformin + OC. No significant differences were seen on hirsutism, FSH, LH, triglycerides and insulin between treatments. Due to the limited number of studies reporting quality of life measures, this outcome could not be analyzed.

Conclusion
Our study suggests that combination treatments in patients with PCOS result in a greater reduction of testosterone levels when compared to monotherapies. The varied efficacy among treatment groups on other relevant outcomes highlights the importance of shared decision making, focusing on each patient's metabolic and hormonal profile, as well as their values and preferences.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.