Metformin and lifestyle modification in polycysticovary syndrome: Systematic review and meta-analysis

Abstract

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with diverse reproductive and metabolic features. It is underpinned by insulin resistance that is exacerbated by obesity. Lifestyle modification is the first line treatment in PCOS, but it is associated with lowadherence and sustainability. In small studies, metformin improves outcomes such as hyperinsulinaemia, ovulation and menstrual cyclicity. We conducted a systematic review and meta-analysis to compare the effect of lifestyle modification + metformin with lifestyle modification ± placebo, and of metformin alone with lifestyle modification ± placebo in PCOS on anthropometric, metabolic, reproductive and psychological outcomes. Methods: Databases including MEDLINE, EMBASE, Pubmed, Scopus, Cochrane, PsycINFO, CINAHL, Clinical Trials registry and ANZCTR were searched for RCTs conducted on humans and published in English up to August 2014. Inclusion criteria were diagnosis of PCOS based on Rotterdam criteria (inclusive of National Institutes of Health criteria) at any age and with any BMI. Interventions of interest included lifestyle + metformin (with any dose and any duration) or metformin alone compared with lifestyle ± placebo. Results: Of 2372 identified studies, 12 RCTs were included for analysis comprising 608 women with PCOS. Lifestyle + metformin were associated with lowerBMI (mean difference (MD) 20.73 kg/m2, 95%confidence intervals (CI) 21.14, 20.32, P = 0.0005) and subcutaneous adipose tissue (MD 292.49 cm2, 95%CI 2164.14, 220.84, P 1/4 0.01) and increased number of menstrual cycles (MD1.06, 95%CI 0.30, 1.82, P 1/4 0.006) after 6 months compared with lifestyle ± placebo. There were no differences in other anthropometric, metabolic (surrogate markers of insulin resistance, fasting and area under the curve glucose, lipids and blood pressure), reproductive (clinical and biochemical hyperandrogenism), and psychological (quality of life) outcomes after 6 months between lifestyle + metformin compared with lifestyle ± placebo.With metformin alone compared with lifestyle ± placebo, weight and BMI were similar after 6 months, but testosterone was lower with metformin. Conclusion: Lifestyle ± metformin is associated with lower BMI and ubcutaneous adipose tissue and mproved menstruation in women with PCOS compared with ifestyle ± placebo over 6 months. etformin alone compared with ifestyle showed similar BMI at 6 months. These results suggest the combination of ifestyle with metformin has a role to play in weight Management: a key oncern for women with PCOS. Existing study limitations include small sample sizes, short durations and risk of ias. With international guidelines ow acknowledging that lifestyle and pharmacotherapy are required for eight loss and maintenance in besity, future studies of appropriate size and duration are vital to clarify the role of metformin in PCOS management.