Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

The marked sexual dimorphism that exists in human cardiovascular diseases has led to the dogmatic concept that testosterone (Tes) has deleterious effects and exacerbates the development of cardiovascular disease in males. While some animal studies suggest that Tes does exert deleterious effects by enhancing vascular tone through acute or chronic mechanisms, accumulating evidence suggests that Tes and other androgens exert beneficial effects by inducing rapid vasorelaxation of vascular smooth muscle through nongenomic mechanisms. While this effect frequently has been observed in large arteries at micromolar concentrations, more recent studies have reported vasorelaxation of smaller resistance arteries at nanomolar (physiological) concentrations. The key mechanism underlying Tes-induced vasorelaxation appears to be the modulation of vascular smooth muscle ion channel function, particularly the inactivation of L-type voltage-operated Ca2+ channels and/or the activation of voltage-operated and Ca2+-activated K+ channels. Studies employing Tes analogs and metabolites reveal that androgen-induced vasodilation is a structurally specific nongenomic effect that is fundamentally different than the genomic effects on reproductive targets. For example, 5α-dihydrotestosterone exhibits potent genomic-androgenic effects but only moderate vasorelaxing activity, whereas its isomer 5β-dihydrotestosterone is devoid of androgenic effects but is a highly efficacious vasodilator. These findings suggest that the dihydro-metabolites of Tes or other androgen analogs devoid of androgenic or estrogenic effects could have useful therapeutic roles in hypertension, erectile dysfunction, prostatic ischemia, or other vascular dysfunctions

Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids

Background Anabolic androgenic steroids are used by some bodybuilders to enhance performance. While the cardiovascular implications of supraphysiological androgen levels requires further clarification, use is associated with sudden death, left ventricular hypertrophy, thrombo-embolism and cerebro-vascular events. Materials and methods To further understand the effect of androgenic anabolic steroid abuse on vascular function, this study assessed vascular stiffness (pulse-wave analysis) and cardiovascular risk factors in 28 male, bodybuilding subjects, of whom ten were actively receiving anabolic agents (group A; 26·4 ± 7·2 years) and eight had undergone a 3-month ‘wash-out’ period (group B; 32·1 ± 7·1 years). The remaining ten bodybuilding subjects (group C; 24·4 ± 4·4 years) denied any past use of anabolic steroids or other performance enhancing drugs. Comparisons were made with ten sedentary male controls (group D, 29·3 ± 4·7 years). Results Endothelial independent dilatation in response to glycerol trinitrate was significantly impaired in the group currently using anabolic steroids (group A) compared with the other three groups [A (5·63 ± 3·24%) versus; B (11·10 ± 4·91%), C (17·88 ± 9·2%) and D (14·46 ± 3·9%), P < 0·0005, respectively], whereas no significant differences in endothelial-dependant dilatation were detected between the groups [A (5·0 ± 3·0%), B (7·4 ± 3·4%), C (9·6 ± 4·5%) and D (8·2 ± 3·3%), P < 0·059, respectively]. Conclusions Previous studies described a decline in vascular reactivity occurring in bodybuilding subjects which is independent of anabolic steroid use and may result from smooth muscle hypertrophy with increased vascular stiffness. This study revealed impaired vascular reactivity associated with anabolic agents and that improvement in vascular function may occur following their discontinuation