Update of the position paper on arterial hypertension and erectile dysfunction.

: Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.

Abnormal deep dorsal vein resulting in veno-occlusive erectile dysfunction.

A 59-year-old man with a 6-year history of erectile dysfunction presented to the andrology outpatient clinic. Multimodality assessment with ultrasound, MRI venography and fluoroscopic venography demonstrated an aberrant emissary vein arising from the corporal bodies causing venogenic erectile dysfunction. Selective coil embolisation of the collateral vein resulted in an almost immediate and sustained improvement in his erections.

Role of disturbed fatty acids metabolism in the pathophysiology of diabetic erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction (VED) is considered as a common complication among people with type 2 diabetes (T2D). We tested whether changes in fatty acid (FAs) classes measured in erythrocytes are associated with increased risk of diabetic VED along with related risk factors. METHODS: We assessed erythrocyte FAs composition, lipid peroxidation parameters and inflammatory cytokines among 72 T2D men with VED, 78 T2D men without VED and 88 healthy volunteers with similar age. Biochemical, hepatic, lipid and hormonal profiles were measured. RESULTS: T2D people with VED had significant decrease in the indexes of Δ6-desaturase and elongase activities compared to the other studied groups. The same group of participants displayed lower erythrocytes levels of dihomo-γ-linolenic acid (C20:3n-6) (P < .001), precursor of the messenger molecule PGE1 mainly involved in promoting erection. Moreover, absolute SFAs concentration and HOMA IR levels were higher in T2D people with VED when compared to controls and associated with impaired NO concentration (1.43 vs 3.30 ng/L, P < .001). Our results showed that IL-6 and TNF-α were significantly increased and positively correlated with MDA levels only in T2D people with VED (r = 0.884, P = .016 and r = 0.753, P = .035; respectively) suggesting a decrease in the relative availability of vasodilator mediators and an activation of vasoconstrictors release. CONCLUSION: Our findings show that the deranged FAs metabolism represents a potential marker of VED in progress, or at least an indicator of increased risk within men with T2D.

Prognostic utility of erectile dysfunction for cardiovascular disease in younger men and those with diabetes.

Multiple published studies have established erectile dysfunction (ED) as an independent risk marker for cardiovascular disease (CVD). In fact, incident ED has a similar or greater predictive value for cardiovascular events than traditional risk factors including smoking, hyperlipidemia, and family history of myocardial infarction. Here, we review evidence that supports ED as a particularly significant harbinger of CVD in 2 populations: men <60 years of age and those with diabetes. Although addition of ED to the Framingham Risk Score only modestly improved the 10-year predictive capacity of the Framingham Risk Score for myocardial infarction or coronary death data in men enrolled in the Massachusetts Male Aging Study, other epidemiologic studies suggest that the predictive value of ED is quite strong in younger men. Indeed, in the Olmstead County Study, men 40 to 49 years of age with ED had a 50-fold higher incidence of new-incident coronary artery disease than those without ED. However, ED had less predictive value (5-fold increased risk) for coronary artery disease in men 70 years and older. Several studies, including a large analysis of more than 6300 men enrolled in the ADVANCE study, suggest that ED is a particularly powerful predictor of CVD in diabetic men as well. Based on the literature reviewed here, we encourage physicians to inquire about ED symptoms in all men more than 30 years of age with cardiovascular risk factors. Identification of ED, particularly in men <60 years old and those with diabetes, represents an important first step toward CVD risk detection and reduction.

Dietary antioxidants improve arteriogenic erectile dysfunction.

Most cases of erectile dysfunction (ED) are associated with oxidative stress risk factors such as diabetes mellitus, smoking, hypercholesterolaemia and hypertension. Our goal was to search for markers of oxidative stress in arteriogenic ED and examine the protective role of dietary antioxidants. Atherosclerosis-induced ED was developed in rabbits by balloon de-endothelialization of the iliac arteries. Ballooned and age-matched control animals were assigned into subgroups receiving pomegranate extract antioxidants in drinking water or tap water as placebo. After 8 weeks, penile blood flow and erectile activity were recorded. Erectile tissue relaxation, oxidative products, oxidative stress-responsive genes and structure were examined using organ bath, enzyme immunoassay, quantitative real-time polymerase chain reaction and transmission electron microscopy, respectively. Arterial ballooning caused diffused atherosclerosis, decreased intracavernosal blood flow and led to ED. Impairment of endothelium-dependent relaxation, diffused fibrosis, increased oxidative products, upregulation of superoxide dismutase (SOD) and aldose reductase (AR) gene expression, mitochondrial and endothelial structural damage and increased caveolae were evident in erectile tissues from atherosclerotic animals receiving placebo. Upregulation of antioxidant enzymes SOD and AR failed to protect ischaemic erectile tissue from oxidative injury. Pomegranate extract significantly improved intracavernosal blood flow, erectile activity, smooth muscle relaxation and fibrosis of the atherosclerotic group in comparison with the atherosclerotic group receiving placebo, but did not normalize them to the age-matched control levels. Pomegranate extract appeared more effective in diminishing oxidative products, preventing SOD and AR gene upregulation, and protecting mitochondrial, endothelial and caveolae structural integrity of the atherosclerotic group. Our data suggest the presence of oxidative stress in ED and a more efficient action of antioxidants on molecular and ultrastructural alterations than on distinct functional deficit and structural damage in the ischaemic penis.

[Nebido in the treatment of hypogonadism syndrome and its complications in men].

The article presents original experience with use of undecanoate (nebido, BayerHealthcare Pharmaceuticals, Germany) in androgenic testosteron replacement therapy in males with hypogonadism. Prospective studies of nebido efficacy were made in males with vein-occlusive erectile dysfunction (n = 20), chronic pelvic pain syndrome (n = 77), metabolic syndrome (n = 170). Retrospective studies assessed efficacy of nebido monotherapy in patients with erectile dysfunction and hypogonadism (n = 34), hematological and urological safety of the drug (n = 40). Laboratory monitoring was performed in all the studies according to ISSAM recommendations. The patients were not included in contraindications to androgenic therapy. Nebido treatment significantly improved libido and erectile function, efficacy of phosphodiesterase of type 5 inhibiors used in moderate and severe erectile dysfunction. Depressive, asthenic, pain symptoms declined in males with chronic pelvic pain. Body fat reduced in metabolic syndrome with alleviation of its other components. Insignificant rise of hemoglobin level and packed cell volume was observed in some patients while a PSA level increase was clinically significant in 10% patients who had initial PSA > 2.5 ng/ml and acromegalia. Also, nebido depressed production of gonadotropins and spermatogenesis. Thus, nebido is highly effective in sexual dysfunction and other somatic disorders caused by hypogonadism. Nebido does not induce severe side effects, but clinically significant rise of PSA level requires treatment discontinuation and more careful urological examination. In view of nebido ability to suppress spermatogenesis, the drug should not be used in reproductively active men.

Persistent erectile dysfunction following radical prostatectomy: the association between nerve-sparing status and the prevalence and chronology of venous leak.

INTRODUCTION: . Failure to recover erectile function after radical prostatectomy (RP) may result from venous leak as a sequela of neuropraxia-induced erectile tissue damage. Venous leak portends a poor prognosis for erections recovery as well as phosphodiesterase type 5 inhibitor (PDE5i) response. AIMS: To define the impact of RP nerve-sparing status on venous leak prevalence and chronology. STUDY POPULATION: men who underwent RP for localized prostate cancer, had functional erections prior to RP, developed postoperative erectile dysfunction (ED), had a Doppler ultrasonography within 6 months of RP, and did not receive any ED treatment for the first 6 months after RP other than on-demand PDE5i. MAIN OUTCOME MEASURES: Venous leak prevalence and erectile function recovery at different time-points. RESULTS: Data on 142 patients were analyzed, mean age: 58 +/- 16 years. Sixty percent had bilateral nerve-sparing (BNS) surgery, 20% unilateral nerve-sparing (UNS) surgery, and 20% non-nerve-sparing (NNS) surgery. Eleven percent and 21% had venous leak by 3 and 6 months, respectively. Venous leak prevalence by 6 months was 7%, 11%, and 75% for BNS, UNS, and NNS surgery (P < 0.001). Mean end-diastolic velocity was 1.8, 2.1, and 7.2 cm/second for the three groups (P < 0.01). The only patients developing venous leak prior to 3 months were NNS patients, one-third of NNS-associated venous leak occurring before this time-point. At 18 months, the proportion of men having return of unassisted erections was 49%, 42%, and 7% with mean erectile function domain scores of 21, 18, and 12, and PDE5i response rates were 72%, 64%, and 12% for the three groups, respectively. CONCLUSIONS: Nerve-sparing status impacts heavily upon the prevalence and the chronology of venous leak development post-RP. NNS RP is associated with early development of venous leak, increased prevalence of venous leak, and reduction in return of natural erections.

Lower urinary tract symptoms and sexual dysfunction: a common approach.

Alpha(1)-adrenergic blockers (alpha(1)-blockers) are considered the most effective monotherapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia. Phosphodiesterase type-5 (PDE-5) inhibitors are the first-line treatment for erectile dysfunction (ED). As LUTS and ED are strongly linked, co-prescription of both drug classes is likely to increase. Interaction studies have confirmed that tadalafil, a long-acting PDE-5 inhibitor, has only marginal effects on blood pressure when co-administered with the selective alpha(1)-blockers, alfuzosin or tamsulosin. alpha(1)-blockers show an incidence of ED similar to placebo; they may even have some benefit on sexual function in men with concomitant LUTS and sexual dysfunction, with the exception of tamsulosin which causes anejaculation. On the other hand, PDE-5 inhibitors have a beneficial effect on LUTS. These agents are likely to act via different mechanisms of action, providing the rationale for combining them to treat LUTS and ED. Indeed, alfuzosin and tadalafil show an additive relaxant effect on human detrusor muscle, human prostate tissue and human corpus cavernosum in vitro. A pilot study also suggests that daily intake of alfuzosin 10 mg and sildenafil 25 mg is well tolerated and may be more effective than monotherapy to improve LUTS and ED. Further research is warranted to establish the value of this combination therapy in LUTS and ED.

Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease.

Since the discovery of sildenafil in 1989 as a highly selective inhibitor of the phosphodiesterase type-5 (PDE-5) receptor, 2 additional PDE-5 inhibitors, tadalafil and vardenafil, have emerged as safe and effective treatments of erectile dysfunction (ED). Enzymes in the PDE family catalyze the hydrolysis of the intracellular signaling molecules cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which is the second messenger of nitric oxide (NO) and a principal mediator of smooth muscle relaxation and vasodilation. Sildenafil was initially introduced for clinical use as the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Erection is largely a hemodynamic event, which is regulated by vascular tone and blood flow balance in the penis. Endothelial dysfunction, an early component of atherosclerosis, may inhibit a vascular event such as erection and is rarely confined to the arteries supplying blood to the penis, but more likely occurs throughout the vascular bed. In addition to the effects of the NO-cGMP signaling pathway on cavernosal smooth muscle, clinical findings have suggested that vascular tone in the pulmonary, coronary, and other vascular tissues expressed by PDE-5 is also influenced by this signal transduction mechanism. This has led to the emergence of novel therapeutic indications for sildenafil over a range of cardiovascular conditions that are either well-established risk factors or comorbidities with ED. Recently, the U.S. Food and Drug Administration approved sildenafil as an orally active therapy for the treatment of primary pulmonary hypertension. The drug will be marketed under the trade name of Revatio, not Viagra, the name used for the ED indication. The approved dose for primary pulmonary hypertension is 20 mg 3 times daily.

Presence of LDL modified by myeloperoxidase in the penis in patients with vascular erectile dysfunction: a preliminary study.

OBJECTIVE: Erectile dysfunction (ED) is a major vascular disorder. Atherosclerosis is closely related to lipoprotein metabolism and especially, oxidative modifications of low-density lipoproteins (LDLs), which are involved in early development of the atherosclerotic lesions. Current major questions include how LDLs are oxidised (OxLDL) in vivo. Myeloperoxidase (MPO) is an enzyme present in the azurophile granules of neutrophils and monocytes that can contribute to LDL oxidation in the presence of H(2)O(2). We have developed a new monoclonal antibody against LDL modified by MPO (Mox-LDL) and have used it on penile biopsies from patients operated on for penile implant. METHODS: Seven patients with vascular ED and one impotent patient after radical prostatectomy (RP) underwent biopsy of the cavernous body during penile implant procedures. An immunohistochemical study with a monoclonal antibody against Mox-LDL and an antibody against apoprotein B (ApoB), the protein moiety of LDL, to confirm the presence of LDL was performed. RESULTS: The staining was positive for Mox-LDL and ApoB and was present between the endothelial cells of the sinusoid spaces and the smooth muscle cells in the seven patients with vascular ED. The patient with RP was negative for Mox-LDL. DISCUSSION: Because it is known that modified LDL could decrease nitric oxide production, Mox-LDL could be one of the agents responsible for ED. Further studies are needed to confirm this hypothesis.

Incidentally diagnosed Peyronie's disease in men presenting with erectile dysfunction.

The aim of this study was to analyze characteristics of patients with Peyronie's disease (PD) diagnosed during a standard evaluation for erectile dysfunction (ED) and compare them with patients presenting with the classical complaints of PD. During a 10-y period, a total of 448 patients were evaluated at our two outpatient clinics, directed by the same author (AK). They were divided into two groups: group I consisted of patients, who presented with only ED and were unaware of their penile deformity, and group II consisted of patients with the classical features of the disease. The clinical characteristics, penile deformities, erectile status and the presence of comorbidities were determined in the two groups. Of 448 Peyronie's patients, 16% (n=71) were detected during diagnostic work-up for ED. In this group of patients, ED was the presenting symptom for a mean period of 31.3+/-9.7 months. The mean age of men was 57.54+/-8.75 and 52.21+/-10.27 y in groups I and II, respectively (P=0.0001). The mean degree of deformity was 31.5+/-12.66 degrees in group I and 41.16+/-19.14 degrees in group II (P=0.0001). In group I (n=71), 69% (n=49) of the patients had a poor erectile response to the combined injection and stimulation (CIS) test. Also, in this group, the mean degrees of deformity in CIS-positive and -negative patients were 27.05+/-12.50 and 33.80+/-12.03 degrees , respectively (P=0.033). Diabetes mellitus (40%) was the leading comorbidity in group I, while at least one comorbidity was observed in 73% of the cases (P=0.001). A remarkable percent of Peyronie's patients (16%) were detected during a standard evaluation for ED. This study analyzed, for the first time, the frequency and the characteristics of incidentally diagnosed Peyronie's patients who presented with only ED. Our data indicate that one should always consider the possibility of PD in older patients with diabetes, presenting with only ED.

Penile colour duplex ultrasonography as a screening tool for venogenic erectile dysfunction.

INTRODUCTION: Vasculogenic impotence is one of the major causes of erectile dysfunction. Cavernosometry and cavernosography is traditionally the gold standard for evaluation of venogenic impotence. However, it is invasive and there are potentially significant complications. Penile colour flow Doppler imaging (PCDI) is non-invasive and can be used to assess venous incompetence. MATERIALS AND METHODS: One hundred and sixty-eight patients were referred for PCDI assessment from March 1998 to February 2001. Forty-three of these also had cavernosogram and cavernosometry done and were included in the study. RESULTS: The sensitivity was 93.9%, the specificity was 90.0%, the accuracy was 93.0% with a negative predictive value of 81.8% and a positive predictive value of 96.9%. Kappa value of 0.81 was obtained, indicating excellent agreement between PCDI and cavernosogram and cavernometry. CONCLUSIONS: Penile colour flow Doppler imaging is accurate in the assessment of venogenic erectile dysfunction. It can replace cavernometry and cavernosogram as a screening tool. Cavernometry and cavernosogram should only be done in cases when PCDI suggests venogenic impotence, and when surgery is contemplated.

Hemodynamic characterization of a functional erection. Arterial and corporeal veno-occlusive function in patients with a positive intracavernosal injection test.

OBJECTIVES: To characterize hemodynamically a functional/rigid erection and study the hypothesis that a positive intracavernosal injection test indicates normal arterial and corporeal veno-occlusive function. METHODS: 33 patients (mean age 39.5 +/- 9 years), who developed rigid erection during pharmacocavernosometry, included in the present study. The presence of axial rigidity was determined at steady state equilibrium intracavernosal pressure, by absence of buckling to axial force of 1 kg, applied to the erect penis and sustained for >/=15 min. Arterial and veno-occlusive hemodynamic parameters were analyzed. RESULTS: Flow-to-maintain at intracavernosal pressure 150 mm Hg and mean pressure decay values ranged between 0.5-13 ml/min and 5-85 mm Hg, respectively. Flow-to-maintain values >5 ml/min were noticed in 8 patients (24. 24%), while pressure decay values >45 mm Hg in 13 patients (39.39%). Pharmacocavernosography revealed moderate opacification of venous structures in 7 cases (21.21%). Abnormal systemic-cavernosal systolic arterial pressure gradients in both cavernosal arteries were noticed in 9 patients (27.27%). All patients with flow-to-maintain values >5 ml/min had normal arterial function. CONCLUSIONS: A functional/rigid erectile response may coexist with arterial insufficiency or corporeal veno-occlusive dysfunction. Presence of normal or borderline arterial inflow may compensate minimal or moderate veno-occlusive dysfunction, resulting in a functional - but not normal - erection. Such information is critical when the intracavernosal injection test is used for diagnostic purposes.

Effects of ultraviolet light on the tension of isolated human cavernosal smooth muscle from non-diabetic and diabetic impotent men.

The effects of ultraviolet (UV) light (310 nm) on human cavernosal smooth muscles were investigated. Cavernosal strips were obtained from men during penile prosthetic surgery. When the cavernosal strips were irradiated with UV light in an organ bath, after precontraction by norepinephrine (100 nM) for 10, 20, 40 and 90 s at intervals of 3 min, the contracted cavernosal smooth muscles from the impotent men without vascular risk factors (controls) showed relaxation depending on the duration of irradiation. However, the relaxation was not found when the strips were pretreated with methylene blue (10 microM) or their epithelia were denuded. The relaxation response of the cavernosal strips from the patients with diabetogenic impotence was significantly reduced compared with that of the controls. Photorelaxation of human cavernosal strips therefore seems to be dependent on endothelium.