Androgens and Erectile Dysfunction with Viagra Au

June 4, 2014 admin Erectile Disfunction

Testosterone in Peripheral Nerves

In animal studies, androgen receptors are found in peripheral nerves that appear responsible for mediating penile erections. Baba et al. showed that NADPH diaphorase staining of nerve fibers in the rat corpus cavernosum and dorsal nerve are dependent on androgens. In a rat model, Armagan et al. demonstrated that T has a neuroprotective role in the nerve fibers of the dorsal nerve, as T deficiency led to nerve degeneration, resulting in anatomic alterations, and erectile dysfunction with viagra australia online pharmacy.

Rogers et al. showed that castration altered the dorsal nerve ultrastructure in the rat. In tissue from castrated rats, the diameter of both the myelinated and nonmyelinated axons appeared smaller than those of control group. Testosterone treatment of castrated animals restored the nerve fibers and myelin sheath structure similar to that observed in the sham group, suggesting that androgens are important in maintaining the peripheral autonomic and sensory nerve structure and function in the penis. Recently, Traish et al. reported similar results for the cavernous nerve.

Giuliano et al. suggested that testosterone enhances the erectile response of the cavernous nerve. The authors suggest that androgen action on nerves may be of even greater importance than its actions on penile erectile tissue. In particular, postganglionic parasympathetic ganglions may be a key site for androgenic proerectile response. In elegant experiments, Meusburger and Keast and Keast et al., demonstrated the role of androgens in maintaining the structure and function of pelvic ganglion neurons.

In 1992, Rajfer et al. elucidated the role of nitric oxide (NO) as the chemical mediator of penile erection. Burnett et al. localized NO to the cavernosal nerve and suggested that NO was the neurotransmitter that initiated penile erection. More recently, animal studies have shown that nitric oxide synthase (NOS) is regulated by the testosterone metabolite, DHT. These results provide critical evidence supporting not only the importance of androgens in control of erectile function, but also that its influence is mediated at least in part by its trophic effects on peripheral nerves.

Testosterone and the Vasculature

In 1939, Edwards et al. were the first to report the effects of testosterone on blood vessels. They observed that testosterone treatment in castrated men was associated with an increased arterialization of the cutaneous vasculature.

Testosterone deficiency has been shown to be an independent determinant of endothelial dysfunction, thus contributing to vascular pathology and ED canadian pharmacy viagra. One mechanism by which testosterone may contribute to ED on a vascular basis is via the nitric oxide pathway. Nitric oxide causes relaxation of the vascular smooth muscle, which leads to penile erection. The role of androgens on the expression of NOS isoforms in the penile tissue has been clearly demonstrated. Castrated animals have a greatly diminished erectile response to direct nerve stimulation, and replacement with testosterone or DHT restored erectile function, as well as NOS expression in the corpora cavernosa. Experimental work suggests that androgen deficiency causes injury to the endothelial lining of the vascular bed of the penis, with decreased NO secretion, but increased synthesis of transform-ing growth factor beta 1 (TGF-b1), endothelin, and contractile prostanoids.

The critical role of testosterone for optimal vascular response with erections was suggested in a study by Aversa et al. This study was comprised of 20 men with arteriogenic ED who had normal sexual desire, but low-normal testosterone (mean total testosterone 368 ng/dl and mean free testosterone 0.75 ng/dl) and who did not respond to the PDE5i sildenafil despite multiple attempts. Men were randomized to receive placebo or transdermal testosterone (5 mg/day) for 1 month. After taking sildenafil 100 mg, the arterial inflow to the cavernous arteries, as measured by dynamic color duplex ultrasound, was significantly greater in patients receiving testosterone than in those receiving placebo. Moreover, a significant association was found between free testosterone concentration and cavernous vasodilation as assessed by duplex ultrasound in eugonadal men with ED (r = 0.37, P < 0.01).

These results provide evidence that testosterone has direct vascular effects on NO-mediated vasodilation. Additional studies have also shown increased penile arterial inflow with testosterone administration together with improved erectile response to both sildenafil and tadalafil.

An additional mechanism by which testosterone may enhance erections is by attenuating the a-adrenergic vasoconstrictor activity in vascular smooth muscles of the corpus cavernosum. Reilly et al. showed that the responsiveness to phenylephrine, an a-adrenergic agonist, was nearly six times greater in castrated rats than those with normal testosterone levels.