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Evidence That Parenteral Testosterone Therapy May Improve Endothelium-Dependent and -Independent Vasodilation in Postmenopausal Women Already Receiving Estrogen

The Jean Hailes Foundation (S.W., S.R.D.), Clayton 3168, Vic; and Department of Vascular Medicine (D.K., H.T., B.M.), Monash University, Clayton, Vic, Australia

Address correspondence and requests for reprints to: Susan R. Davis, Associate Professor, Director of Research, The Jean Hailes Foundation, 173 Carinish Road, Clayton 3168, Australia. E-mail: suedavis{at}netlink

The gender difference in cardiovascular disease has been partly attributed to higher androgenic hormone levels. Although testosterone in women may not affect lipids, it remains unknown whether it negates favorable estrogenic effects on endothelial function. We have investigated the effects of testosterone implant therapy on arterial reactivity encompassing endothelial-dependent and -independent vasodilation in women using hormone replacement therapy (HRT). B-mode ultrasound measurements of resting brachial artery diameter, following reactive hyperemia [endothelium-dependent flow- mediated dilation (FMD)] and following glyceryl trinitrate (GTN) (endothelium-independent dilation), were recorded in 33 postmenopausal women stabilized on HRT (>6 months), at baseline, and 6 weeks after a testosterone implant (50 mg), with 15 postmenopausal nonusers of HRT serving as controls. In the brachial artery, baseline resting diameter was similar (0.40 ± 0.01 vs. 0.41 ± 0.01 cm, P = 0.5). In the treated group, testosterone levels increased (0.99 ± 0.08 to 4.99 ± 0.3 nmol/L, P < 0.001), associated with a mean 42% increase in FMD (6.4% ± 0.7 to 9.1% ± 1.1, P = 0.03). The control group did not change (8.1% ± 1.4 to 5.6% ± 1.0, P = 0.4). ANOVA of repeated measures (P = 0.04) and mean change (P = 0.02) in FMD both demonstrated significantly greater improvement with testosterone compared with controls. GTN induced vasodilation increased with testosterone treatment (14.9% ± 0.9 to 17.8% ± 1.2, P = 0.03). Our preliminary data indicate that parenteral testosterone therapy improves both endothelial-dependent (flow-mediated) and endothelium-independent (GTN-mediated) brachial artery vasodilation in postmenopausal women using long-term estrogen therapy. The mechanisms underlying these potentially beneficial cardiovascular effects require further investigation.

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