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.
OBJECTIVE
To 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.


METHODS
Placebo-controlled, randomized clinical trial.


METHODS
Academic clinical research center.


METHODS
Fifty-two HIV-infected, menstruating women with >5% weight loss over the prior 6 months and current T<33 ng/dL.


METHODS
Placebo or T patches twice weekly for 24 weeks to achieve nominal delivery of 300 microg T daily.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Herbst
Karen L
KL
Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA. Karen.herbst@med.va.gov
Calof
Olga M
OM
Hsia
Stanley H
SH
Sinha-Hikim
Indrani
I
Woodhouse
Linda J
LJ
Buchanan
Thomas A
TA
Bhasin
Shalender
S
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D050218:Body Fat Distribution / Q000706:statistics & numerical data*; D002140:California / Q000453:epidemiology; D015897:Comorbidity; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000503:physiopathology*; D020249:Hormone Replacement Therapy / Q000706:statistics & numerical data*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000453:epidemiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D015990:Placebo Effect; D012720:Severity of Illness Index; D013739:Testosterone / Q000008:administration & dosage*; D013927:Thrombosis / Q000097:blood / Q000453:epidemiology; D015431:Weight Loss
D015415:Biomarkers; D016207:Cytokines; D007328:Insulin; D013739:Testosterone