Insulin Sensitizers for the Treatment of Hirsutism: A Systematic Review and Meta-analyses of Randomized Controlled Trials.

Author(s): Cosma M, Swiglo BA, Flynn DN, Kurtz DM, Labella ML, Mullan RJ, Elamin MB, Erwin PJ, Montori VM

Affiliation(s): Knowledge and Encounter Research Unit, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota; Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota; Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota; State University of New York at Geneseo, Geneseo, New York.

Publication date & source: 2008-02-05, J Clin Endocrinol Metab., [Epub ahead of print]

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: To conduct a systematic review and meta-analyses 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 >/= 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 meta-analyses showed a small decrease in Ferriman-Gallwey scores in women treated with insulin sensitizers compared to placebo (pooled weighted mean difference (WMD) of -1.5, 95% confidence interval (CI) -2.8, -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%). 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.