Insulin sensitizers for the treatment of hirsutism: A systematic review and metaanalyses of randomized controlled trials

Context: Insulin sensitizers, including metformin and thiazolidinediones (TZDs), improve hyperinsulinemia and reproductive dysfunctions in some women with hyperandrogenism. The extent to which these agents improve hirsutism remains unclear. Objective: Our objective was to conduct a systematic review and metaanalyses of randomized controlled trials of metformin or TZDs for the treatment of hirsutism. Data Sources: We searched the following databases: MEDLINE, EMBASE, and Cochrane CENTRAL (up to May 2006). Review of reference lists and contact with hirsutism experts further identified candidate trials. Study Selection: Reviewers working independently and in duplicate, with acceptable chance-adjusted agreement (kappa = 0.72), determined trial eligibility. Eligible trials randomly assigned women with hirsutism to at least 6 months of insulin sensitizers or control and measured hirsutism outcomes. Data Extraction: Reviewers working independently and in duplicate determined the methodological quality of trials and collected data on patient characteristics, interventions, and outcomes. Data Synthesis: Of 348 candidate studies, 16 trials (22 comparisons) were eligible. The methodological quality of these trials was low. Random-effects metaanalyses showed a small decrease in Ferriman-Gallwey scores in women treated with insulin sensitizers compared with placebo [pooled weighted mean difference (WMD) of -1.5; 95% confidence interval (CI), -2.8 to -0.2; inconsistency (I-2) = 75%]. There was no significant difference between insulin sensitizers and oral contraceptives (WMD of -0.5; CI, -5.0, 3.9; I-2 -79%). Metform in was inferior to both spironolactone (WMD of 1.3; CI, 0.03, 2.6) and flutamide (WMD of 5.0; CI, 3.0, 7.0; I-2 = 0%). Conclusions: Imprecise and inconsistent evidence of low to very low quality suggests that insulin sensitizers provide limited or no important benefit for women with hirsutism.