title: Metformin and lifestyle modification in polycystic ovary 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 low adherence 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 lower BMI (mean difference (MD) -0.73 kg/m(2), 95% confidence intervals (CI) -1.14, -0.32, P = 0.0005) and subcutaneous adipose tissue (MD -92.49 cm(2), 95% CI -164.14, -20.84, P = 0.01) and increased number of menstrual cycles (MD 1.06, 95% CI 0.30, 1.82, P = 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.
  
  
  CONCLUSIONS
  Lifestyle + metformin is associated with lower BMI and subcutaneous adipose tissue and improved menstruation in women with PCOS compared with lifestyle ± placebo over 6 months. Metformin alone compared with lifestyle showed similar BMI at 6 months. These results suggest the combination of lifestyle with metformin has a role to play in weight management: a key concern for women with PCOS. Existing study limitations include small sample sizes, short durations and risk of bias. With international guidelines now acknowledging that lifestyle and pharmacotherapy are required for weight loss and maintenance in obesity, future studies of appropriate size and duration are vital to clarify the role of metformin in PCOS management.
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia Diabetes and Vascular Medicine Unit, Monash Health, Locked Bag 29, Clayton, VIC 3168, Australia.
authors.forename: Negar
authors.initials: N
authors.lastname: Naderpoor
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia Diabetes and Vascular Medicine Unit, Monash Health, Locked Bag 29, Clayton, VIC 3168, Australia.
authors.forename: Soulmaz
authors.initials: S
authors.lastname: Shorakae
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia Diabetes and Vascular Medicine Unit, Monash Health, Locked Bag 29, Clayton, VIC 3168, Australia.
authors.forename: Barbora
authors.initials: B
authors.lastname: de Courten
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia.
authors.forename: Marie L
authors.initials: ML
authors.lastname: Misso
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia Robinson Research Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Moran
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia Diabetes and Vascular Medicine Unit, Monash Health, Locked Bag 29, Clayton, VIC 3168, Australia Robinson Research Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia helena.teede@monash.edu.
authors.forename: Helena J
authors.initials: HJ
authors.lastname: Teede
mesh_terms: D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications; D006946:Hyperinsulinism / Q000150:complications; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications; D010060:Ovulation / Q000502:physiology; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D040242:Risk Reduction Behavior
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: lifestyle; metformin; polycystic ovary syndrome; weight loss