Insulin Sensitizers for the Treatment of Hirsutism: A Systematic Review and Metaanalyses of Randomized Controlled Trials

Abstract

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. Our objective was to conduct a systematic review and metaanalyses of randomized controlled trials of metformin or TZDs for the treatment of hirsutism. 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. 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. Reviewers working independently and in duplicate determined the methodological quality of trials and collected data on patient characteristics, interventions, and outcomes. 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%). Metformin 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%). Imprecise and inconsistent evidence of low to very low quality suggests that insulin sensitizers provide limited or no important benefit for women with hirsutism.