Testosterone dose-response relationships with cardiovascular risk markers in androgen-deficient women: a randomized, placebo-controlled trial.
OBJECTIVE
To determine dose-dependent effects of T administration on cardiovascular risk markers in women with low T levels.


METHODS
Seventy-one hysterectomized women with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3-, 6.25-, 12.5-, or 25-mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Insulin resistance and inflammatory markers were measured at baseline and 24 weeks. In a subset of women, magnetic resonance imaging of the abdomen was performed to quantify abdominal fat volume.


RESULTS
Fifty-nine women who completed the 24-week intervention were included in the final analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 14, 79, 105, 130, and 232 ng/dL in the placebo group and the 3-, 6.25-, 12.5-, and 25-mg groups, respectively. No significant changes in fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, adiponectin, blood pressure, and heart rate were observed at any T dose when compared to placebo. Similarly, no dose- or concentration-dependent changes were observed in abdominal fat on magnetic resonance imaging.


CONCLUSIONS
Short-term T administration over a wide range of doses for 24 weeks in women with low T levels was not associated with worsening of cardiovascular risk markers.
Section of Men's Health: Aging and Metabolism (G.H., M.D., H.S., T.G.T., S.Bh., S.Ba.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Department of Radiology (E.T., A.A., S.A., H.J.), Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118.
Grace
G
Huang
Elizabeth
E
Tang
Adam
A
Aakil
Stephan
S
Anderson
Hernan
H
Jara
Maithili
M
Davda
Helene
H
Stroh
Thomas G
TG
Travison
Shalender
S
Bhasin
Shehzad
S
Basaria
D000328:Adult; D000728:Androgens / Q000172:deficiency*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
D000728:Androgens; D015415:Biomarkers; D010919:Placebos; D013739:Testosterone