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Metformin in polycystic ovary syndrome: systematic review and meta-analysis

BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7421.951 (Published 23 October 2003) Cite this as: BMJ 2003;327:951
  1. Jonathan M Lord, specialist registrar (jonathan.lord{at}pms.ac.uk)1,
  2. Ingrid H K Flight, research officer2,
  3. Robert J Norman, professor3
  1. 1Department of Endocrinology and Metabolism, Peninsula Medical School, South West Centre for Reproductive Medicine, Derriford Hospital, Plymouth, Devon, PL6 8DH
  2. 2Consumer Science Program, Commonwealth Scientific and Industrial Research Organisation, Health Sciences and Nutrition, PO Box 10041, Adelaide, SA 5000, Australia
  3. 3Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, University of Adelaide, Queen Elizabeth Hospital, Woodville Road, Woodville, SA 5005, Australia
  1. Correspondence to: J M Lord
  • Accepted 7 August 2003

Abstract

Objective To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome.

Design Systematic review and meta-analysis.

Data sources Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent.

Selection of studies 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence.

Main outcome measure Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome.

Results Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance.

Conclusions Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.

Footnotes

  • Contributors JML was responsible for the primary literature search, initial assessment of trials and quality analysis, data collection, analysis, and the initial draft of the full review. He acts as guarantor. IHKF was responsible for developing the protocol, checking the literature search, undertaking secondary assessment of trials and quality analysis (blinded), reviewing data collection and analysis, and revising the first draft of the full review. RJN was responsible for developing protocol and was the final arbiter to resolve differences in quality assessment between other reviewers. He contributed to finalising the review and the content and is the Cochrane expert.

  • Funding Reproductive Medicine Unit, University of Adelaide

  • Competing interests None declared

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