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This version published online on February 5, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-2429
A more recent version of this article appeared on April 1, 2008
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Submitted on November 2, 2007
Accepted on January 25, 2008

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

Mihaela Cosma MD, Brian A. Swiglo MD, David N. Flynn BS, David M. Kurtz BS, Matthew L. LaBella, Rebecca J. Mullan MSc, Mohamed B. Elamin MBBS, Patricia J. Erwin MLS, and Victor M. Montori MD, MSc*

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

* To whom correspondence should be addressed. E-mail: montori.victor{at}mayo.edu.

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 (I2) = 75%). There was no significant difference between insulin sensitizers and oral contraceptives (WMD of -0.5, CI, -5.0, 3.9; I2 = 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; I2=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.


Key words: Insulin Sensitizers • Hirsutism • Systematic review • Meta-analysis







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