Eaton CB. Liu YL. Mittleman MA. Miner M. Glasser DB. Rimm EB. A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men. International Journal of Impotence Research. 19(2):218-25, 2007 Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation. We evaluated the cross-sectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good - 28.2%, good - 25.1%, fair - 19.2%, poor - 13.6%, to very poor - 13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P=0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P=0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P=0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P=0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.

Jackson G. The importance of risk factor reduction in erectile dysfunction. [Review] [27 refs] Current Urology Reports. 8(6):463-6, 2007 Erectile dysfunction (ED) is associated with modifiable risk factors. Obesity, physical inactivity, and the metabolic syndrome increase the incidence of ED and markers of low-grade inflammation, which in turn are associated with endothelial dysfunction. Intensive intervention with lifestyle advice focusing on a healthy diet, weight loss, and increased physical activity benefits men with ED, reducing the markers of inflammation and improving endothelial function. Though phosphodiesterase type 5 inhibitors are highly effective in treating ED, lifestyle advice and aggressive risk reduction remain fundamental to the overall vascular good health of the individual.

Aversa A. Vitale C. Volterrani M. Fabbri A. Spera G. Fini M. Rosano GM. Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes. Diabetic Medicine. 25(1):37-44, 2008 OBJECTIVE: Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). METHODS: In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. RESULTS: After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 +/- 0.5 to 12.5 +/- 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. CONCLUSIONS: In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition.

Karadag F. Ozcan H. Karul AB. Ceylan E. Cildag O. Correlates of erectile dysfunction in moderate-to-severe chronic obstructive pulmonary disease patients. Respirology. 12(2):248-53, 2007 OBJECTIVE AND BACKGROUND: Erectile dysfunction (ED) has important negative effects on male quality of life and self-esteem. The aim of this study was to acquire an insight into the sexual status of COPD patients. METHODS: Ninety-five male patients aged 48-75 years, with moderate-to-severe stable COPD, and 30 age-matched subjects with normal pulmonary function were included. After clinical evaluation and measurement of serum sex hormones and TNF-alpha concentration, subjects were asked to answer the International Index of Erectile Function (IIEF) questionnaire as a method to diagnose and classify ED. RESULTS: Varying degrees of ED were detected in 87% of COPD patients and 83% of controls. Although the total percentages of subjects with various severities of ED seemed similar, moderate and severe ED was 57% in COPD group and 20% in control subjects, suggesting a more severe course of ED in COPD patients. ED score of COPD patients was not correlated with age, smoking burden, duration of COPD, FEV1%, PaO2, PaCO2, serum dehydroepiandrosterone-sulphate, testosterone or estradiol levels. When patients were subgrouped according to severity of ED, serum TNF-alpha concentration, used as a marker of systemic inflammatory status in COPD, was significantly higher in patients with moderate-to-severe ED compared with mild-moderate ED. CONCLUSION: The present study showed that ED is frequent and more severe in COPD patients than age-matched controls. Chronic systemic inflammation is likely to play a role in ED in COPD; the role of TNF-alpha should be evaluated further. Patients with COPD need comprehensive management including a detailed sexual evaluation.

Blans MC. Visseren FL. Banga JD. Hoekstra JB. van der Graaf Y. Diepersloot RJ. Bouter KP. Infection induced inflammation is associated with erectile dysfunction in men with diabetes. European Journal of Clinical Investigation. 36(7):497-502, 2006 BACKGROUND: In diabetic patients with erectile dysfunction, endothelial dysfunction is a major underlying cause. Infection-induced inflammation may be associated with endothelial dysfunction. The goal of this study was to determine whether erectile dysfunction in patients with diabetes is associated with infections of Chlamydia pneumoniae or cytomegalovirus and/or with low-grade inflammation. MATERIALS AND METHODS: Diabetic patients, 57 with and 33 without erectile dysfunction, were enrolled in a case-control study. Both groups of patients consists of type 1 and type 2 diabetics. Serum antibodies against cytomegalovirus and C. pneumoniae and markers of inflammation, including high-sensitivity C-reactive protein and fibrinogen, were measured. RESULTS: Adjusted odds ratios for erectile dysfunction in cytomegalovirus IgG, C. pneumoniae IgG and C. pneumoniae IgA seropositive men were 2.4 (95%CI; 1.0-6.0), 3.0 (95%CI; 1.2-8.1) and 1.8 (95%CI; 0.7-4.6), respectively. Odds ratios for the highest tertiles of high-sensitivity C-reactive protein and fibrinogen concentrations compared to the lowest tertile were 4.3 (95%CI; 1.4-13.1) and 6.6 (95%CI; 2.1-21.2), respectively. CONCLUSION: Elevated high-sensitivity C-reactive protein or fibrinogen serum levels and infection with cytomegalovirus or C. pneumoniae were associated with erectile dysfunction in diabetes. The relation between cytomegalovirus and erectile dysfunction is markedly present in patients with elevated high-sensitivity C-reactive protein and fibrinogen levels, suggesting a modifying effect by the inflammation.

Vlachopoulos C. Aznaouridis K. Ioakeimidis N. Rokkas K. Vasiliadou C. Alexopoulos N. Stefanadi E. Askitis A. Stefanadis C. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. European Heart Journal. 27(22):2640-8, 2006 AIMS: Erectile dysfunction (ED) confers an independent cardiovascular risk. We investigated the role of low-grade inflammation and endothelial dysfunction in ED patients with or without coronary artery disease (CAD). METHODS AND RESULTS: We evaluated 141 men (age 58.8 years) for ED and CAD through a rigourous investigation (including coronary angiography to reveal occult CAD). Blood levels of inflammatory (hsCRP, IL-6, IL-1beta, and TNF-alpha) and endothelial-prothrombotic markers/mediators (vWF, tPA, PAI-1, and fibrinogen) were significantly increased in ED patients and correlated negatively with sexual performance. ED was associated with higher levels of these substances (except for IL-6) on top of CAD alone. For most substances, the unfavourable impact of ED alone was not significantly different than the impact of CAD alone. In multivariable models, these markers/mediators predicted independently ED presence. In our population, the negative predictive value of the combination of fibrinogen <225 mg/dL with IL-6 <1.24 pg/mL for excluding ED was 91.7% (95% CI: 61.5-99.8). CONCLUSION: ED is associated with increased inflammatory and endothelial-prothrombotic activation in men with or without CAD. ED confers an incremental unfavourable impact on the circulating levels of these markers/mediators when combined with CAD. These findings have implications for increased cardiovascular risk in ED patients.

Simpson JD. Doux JD. Lee PY. Yun AJ. Peripheral arterial disease: a manifestation of evolutionary dislocation and feed-forward dysfunction. Medical Hypotheses. 67(4):947-50, 2006. Peripheral arterial disease in the legs represents a subset of atherosclerosis that manifests a particularly sinister profile. A predominance of sympathetic activity in the periphery favors the development of neurogenic atherosclerosis. Atherosclerosis may then produce flow derangements and decreased physical activity that serves to escalate sympathetic bias in a vicious cycle. Restoration of normal flow in peripheral arterial disease may not only produce local benefit due to improved perfusion, but also represent a gateway to correcting many systemic conditions that may at first glance appear unrelated but share a common etiology of autonomic dysfunction, such as gout, acute coronary syndromes, stroke, sleep apnea, arrhythmias, depression, erectile dysfunction, inflammation, hypercoagulability, sleep disorders, bowel dysfunction, renal failure, and aging.

Tuncel A. Akbulut Z. Atan A. Basar MM. Common symptoms in men with prostatic inflammation. International Urology & Nephrology. 38(3-4):583-6, 2006. PURPOSE: We evaluated 96 patients with prostatic inflammation in terms of their symptoms and aimed to find common types and frequencies of symptoms in these patients. PATIENTS AND METHODS: The mean age of the patients was 38.0+/-8.7 (range 21-58) years. Physical examination, digital rectal examination, microscopic prostatic secretion assessment and urine cultures after taking a detailed medical history were performed. Urine samples before and after prostatic massage were collected for urine culture. Frequency and types of patients' symptoms were evaluated. All patients were asked about lower urinary tract symptoms, sexual dysfunction and other complaints. RESULTS: Lower urinary tract symptoms and lumbal pain were more prevalent in elder patients. Ejaculation disorder was the most common sexual problem (n=65, 67.7%). Erectile dysfunction and decreased libido were observed in 29 (30.2%) and 22 (22.9%) of the patients. Other complaints were lumbal pain (n=34, 35.4%), perineal fullness (n=50, 52.1%), haemospermia (n=20, 20.8%) and scrotal pain (n=43, 44.8%). CONCLUSION: Prostatic inflammation was usually seen in men of the third and fourth decade. Sexual dysfunction was the most common symptom in this particular group of patients.

Shamloul R. el-Nashaar A. Chronic prostatitis in premature ejaculation: a cohort study in 153 men. Journal of Sexual Medicine. 3(1):150-4, 2006 INTRODUCTION: Premature ejaculation is a common male sexual dysfunction, affecting 30-40% of sexually active men in an age-dependent manner. Chronic prostatitis has been suggested as an important organic cause of premature ejaculation. AIM: The aim of this study was to confirm previous data reported on the incidence of chronic prostatitis in a large cohort of patients with primary and secondary premature ejaculation. METHODS: A total of 153 consecutive heterosexual men aged 29-51 years with premature ejaculation and another 100 male healthy subjects were included in this study. Sequential microbiologic specimens were obtained according to the standardized Meares and Stamey protocol. Nonbacterial prostatitis was defined by the evidence of prostatic inflammation but negative cultures of urine and prostatic fluids in men with various genitourinary symptoms. RESULTS: There was no significant difference between patients and control subjects regarding age, education, or intercourse frequency. Prostatic inflammation was found in 64% and chronic bacterial prostatitis in 52% of the patients with premature ejaculation, respectively, showing statistical significance compared with control subjects (P < 0.05). CONCLUSIONS: Results in our study showed a high prevalence of chronic prostatitis in patients with premature ejaculation. Examination of the prostate, physically and microbiologically, should be considered during assessment of patients with premature ejaculation.

Giugliano F. Esposito K. Di Palo C. Ciotola M. Giugliano G. Marfella R. D'Armiento M. Giugliano D. Erectile dysfunction associates with endothelial dysfunction and raised proinflammatory cytokine levels in obese men. Journal of Endocrinological Investigation. 27(7):665-9, 2004 Erectile and endothelial dysfunction may have some shared pathways through a defect in nitric oxide activity. We evaluated associations between erectile function, endothelial function and markers of systemic vascular inflammation in 80 obese men, aged 35-55 yr, divided into two equal groups according to the presence/absence of erectile dysfunction. Compared with non-obese age-matched men [no.=50, body mass index (BMI)=24 +/- 1], obese men (all) had impaired indices of endothelial function as suggested by the reduced mean blood pressure and platelet aggregation responses to L-arginine, and higher circulating concentrations of the proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), as well as C-reactive protein (CRP). The mean erectile function score was 14 +/- 4 (range 7-19) in obese men with erectile dysfunction and 23.5 +/- 1 (range 22-25) in obese men without erectile dysfunction. Endothelial function showed a greater impairment in impotent obese men as compared with potent obese men. The mean blood pressure and platelet aggregation decreases following L-arginine were -1.5 +/- 1.1 mmHg and -1.1 +/- 1.2%, respectively, in obese men with erectile dysfunction, and -3.4 +/- 1.2 mmHg and -5.6 +/- 2.1%, respectively, in obese men without erectile dysfunction (p < 0.01). Circulating CRP levels were significantly higher in obese men with erectile dysfunction as compared with obese men without erectile dysfunction (p < 0.05). Erectile function score was positively associated with mean blood pressure responses to L-arginine and negatively associated with BMI, waist-to-hip ratio (WHR), and CRR Erectile and endothelial dysfunction associate in obese men and may contribute to their raised cardiovascular risk through impaired nitric oxide availability elicited by a low-grade inflammatory state.

Yudkin JS. Juhan-Vague I. Hawe E. Humphries SE. di Minno G. Margaglione M. Tremoli E. Kooistra T. Morange PE. Lundman P. Mohamed-Ali V. Hamsten A. The HIFMECH Study Group. Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study. Metabolism: Clinical & Experimental. 53(7):852-7, 2004 Risk of coronary heart disease has been related to insulin resistance, but the mechanism for this is incompletely understood. Variables attributed to insulin resistance are associated with low-grade inflammation. A case-control study was performed of 469 male myocardial infarction (MI) survivors aged < 60 years and 575 control subjects recruited from centers in northern and southern Europe. Principal factor analysis was used to explore correlations between insulin resistance and inflammatory variables. Three factors resulted: (a) "Metabolic Syndrome" (insulin/proinsulin/ triglyceride/body mass index [BMI]); (b) "Inflammation" (fibrinogen/C-reactive protein [CRP]/interleukin-6 [IL-6]); and (c) "Blood Pressure" (systolic and diastolic blood pressure). The "Metabolic Syndrome" factor was related to the "Inflammation" factor (largely independently of obesity), the "Blood Pressure" factor, smoking, and south location (all P < or = .0002). There were significant relationships between all 3 factors and case status (P < or = .0002). Markers of low-grade inflammation are strongly related to metabolic syndrome variables independently of obesity. This raises the possibility that links between insulin resistance and cardiovascular disease could, in part, represent common consequences of low-grade inflammation.

Achike FI. Kwan CY. Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway. [Review] [155 refs] Clinical & Experimental Pharmacology & Physiology. 30(9):605-15, 2003 1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or purified drugs derived from Chinese medicinal herbs with proposed actions on NO pathways are also reviewed.