Effects of transdermal testosterone administration on insulin sensitivity, fat mass and distribution, and markers of inflammation and thrombolysis in human immunodeficiency virus–infected women with mild to moderate weight loss

ObjectiveTo determine the effects of raising serum T levels into the high normal female range by transdermal T administration on insulin sensitivity, fat volume, and markers of inflammation and thrombolysis in HIV-infected women with recent weight loss.DesignPlacebo-controlled, randomized clinical trial.SettingAcademic clinical research center.Patient(s)Fifty-two HIV-infected, menstruating women with >5% weight loss over the prior 6 months and current T<33 ng/dL.Intervention(s)Placebo or T patches twice weekly for 24 weeks to achieve nominal delivery of 300 μg T daily.Main Outcome Measure(s)Testosterone by liquid chromatography-tandem mass spectrometry, insulin sensitivity by the frequently sampled intravenous glucose tolerance test (FSIVGT), abdominal and thigh fat volumes by magnetic resonance imaging (MRI), and C-reactive protein (CRP) as a measure of inflammation and plasminogen-activated inhibitor-1 (PAI-1) levels as a marker of thrombolysis.Result(s)Serum and free T levels significantly increased into the high normal female range in T-treated but not placebo-treated women. Insulin sensitivity by FSIVGT, whole body, thigh SC, and intra-abdominal fat volumes, and CRP and PAI-1 levels did not change significantly in either group and were not significantly different between the two groups. Fasting insulin increased in the placebo group and fell slightly in the T group, resulting in significant differences in change between groups.Conclusion(s)Twenty-four weeks of elevation of serum T levels into the high normal female range in HIV-infected women with mild to moderate weight loss by transdermal T patches did not adversely affect insulin sensitivity, whole-body fat mass or regional fat distribution, or markers of inflammation and thrombolysis. More prolonged and larger studies are needed to determine the effects of higher doses of T on body composition and insulin sensitivity in women.