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Erectile dysfunction

October 2005

New oral agents for erectile dysfunction: what is changing in our practice?

Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and is associated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, as well as numerous age-related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A rational step-wise approach which includes comprehensive medical and sexual history, a focused physical examination and essential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnostic work-up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penile pharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate only in the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable risk factors or causes, although frequently insufficient to reverse ED completely. When indicated, oral therapy with new molecules (phosphodiesterase inhibitors or apomorphine) is the first-line treatment for the majority of patients because of potential benefits and lack of invasiveness.

Asian J Androl. 2001 Sep;3(3):175-9

Nutrients and botanicals for erectile dysfunction: examining the evidence.

Erectile dysfunction affects 50% of men ages 40-70 in the United States and is considered an im portant public health problem by the National Institutes of Health. Consumers are exposed to a plethora of natural products claiming to restore erection and sexual vitality. A review of the available empirical evidence reveals most naturally occurring compounds lack adequate clinical trials to support efficacy. However, arginine, yohimbine, Panax ginseng, Maca, and Ginkgo biloba all have some degree of evidence they may be helpful for erectile dysfunction. Improve ments in penile endothelial L-arginine-nitric oxide activity appear to be a unifying explanation for the actions of these naturally occurring agents.

Altern Med Rev. 2004 Mar;9(1):4-16

Neural control of erection.

Activation of sacral parasympathetic pathways elicits penile erection through the release of vasorelaxant neurotransmitters that increase blood flow to the penis and relax the penile erectile tissue. Sympathetic pathways are antierectile. The pudendal pathway, responsible for the contraction of the perineal striated muscles, enhances an already present erection. All pathways originate in the spinal cord, but at various levels and areas. The convergence of information from peripheral and supra-spinal origins onto spinal neurones is very likely activating more specifically the spinal pro-erectile network. Peripheral information is the afferent limb of reflexive erections, impinges onto spinal interneurones and is able to activate or regulate the activity of sympathetic, parasympathetic and somatic nuclei. Supra-spinal information impinges onto either the same or a different spinal network. Premotor neurones located in supra-spinal structures, that project directly onto spinal sympathetic, parasympathetic or pudendal motoneurones, are present in the medulla, pons and diencephalon. Several of these premotor neurones may in turn be activated by sensory information from the genitals. Descending pathways release a variety of aminergic and peptidergic neurotransmitters in the vicinity of spinal neurones, thereby exerting complex effects on the spinal pro-erectile network. Brainstem and hypothalamic nuclei (among the latter, the paraventricular nucleus and the medial preoptic area) may not reach directly the spinal pro-erectile network. They are prone to regulate penile erection in more integrated and coordinated responses of the body, as those occurring during sexual behaviour. The pro-erectile central and spinal effects of neuropeptides such as oxytocin, melanocortins and endorphins have only recently been analyzed. Such compounds may represent therapeutic strategies to treat erectile dysfunction through a central site of action.

J Soc Biol. 2004; 198(3):217-30

The effects of smoking on the reproductive health of men.

This article discusses the impact smoking can have on men’s sexual and reproductive health. There is evidence to suggest that smoking can result in alterations of the male sex hormones and is a key cause of and contributor to erectile dysfunction. Smoking can therefore endanger the man’s ability to have a family and enjoy sexual activity. A reduction in sperm quality and a reduced response to fertility treatments has also been linked with those men who smoke. The damaging effects of smoking are apparent throughout the lifespan of a smoker. The benefits associated with cessation of smoking are wide and varied with respect to the reproductive health of men; these benefits can include a reduction in the risk of male impotence and an improvement in sexual potency.

Br J Nurs. 2005 Apr 14-27;14(7):362-6

Current opinions on the relationships between athero-thrombosis, type 2 diabetes mellitus and erectile dysfunction.

Erectile dysfunction is often associated with diabetes mellitus and athero-thrombotic diseases, such as coronary heart disease, stroke, peripheral vascular disease. An association between erectile dysfunction and asymptomatic coronary artery disease angiographically verified has been recently shown in diabetic patients. Several pathophysiological mechanisms may explain the relationship between erectile dysfunction and athero-thrombosis, especially in diabetic subjects. Among these mechanisms, it is of interest to consider a common pattern of cardiovascular risk factors, the presence of autonomic neuropathy and endothelial dysfunction. The strong association between erectile dysfunction and athero-thrombosis may have some important clinical implications. In particular, erectile dysfunction may be used as a predictor of silent or early athero-thrombotic diseases, especially in diabetic patients.

Recenti Prog Med. 2005 Mar;96(3):155-8

A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis.

OBJECTIVE: Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS). METHODS: This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed. RESULTS: After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE. CONCLUSION: Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.

J Neurol Neurosurg Psychiatry. 2005 May;76(5):700-5

Symptoms of autonomic failure in Parkinson’s disease: prevalence and impact on daily life.

Frequency and clinical importance of autonomic failure in idiopathic Parkinson’s disease (PD) are discussed controversially. 141 patients with PD and 50 healthy age-matched control subjects were interviewed for symptoms of autonomic failure and their influence on daily life using a questionnaire. In PD patients, the prevalence of orthostatic dizziness, bladder dysfunction, erectile dysfunction and hyperhidrosis was significantly higher compared with controls. About 50% of PD patients rated the impact of the symptoms of autonomic failure on their daily lives as “a lot” or “very much” due to orthostatic dizziness, bladder dysfunction and constipation, which were more statistically significant than in age-matched controls. Prevalence and number of autonomic symptoms were not correlated with duration and severity of PD. In 32% of patients, impaired cardiovascular regulation was found by standardized cardiovascular function tests. If testing showed abnormal findings, orthostatic dizziness, bladder dysfunction, constipation and erectile dysfunction were significantly more frequent than in patients with normal regulation, but the impact on daily life due to these symptoms differed significantly only for bladder dysfunction between groups. It is concluded that autonomic failure is a clinically relevant, pervasive problem in PD and compromise patients’ daily life activities in all stages of the disease. This underlines the necessity to adequately search for and treat these non-dopaminergic symptoms during the whole course of the disease.

Clin Auton Res. 2005 Apr;15(2):76-82