Basic Science Evidence for the Link Between Erectile Dysfunction and Cardiometabolic Dysfunction

IntroductionAlthough clinical evidence supports an association between cardiovascular/metabolic diseases (CVMD) and erectile dysfunction (ED), scientific evidence for this link is incompletely elucidated.AimThis study aims to provide scientific evidence for the link between CVMD and ED.MethodsIn this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current literature on basic scientific support for a mechanistic link between ED and CVMD, and deficiencies in this regard with a critical assessment of current preclinical models of disease.ResultsA link exists between ED and CVMD on several grounds: the endothelium (endothelium‐derived nitric oxide and oxidative stress imbalance); smooth muscle (SM) (SM abundance and altered molecular regulation of SM contractility); autonomic innervation (autonomic neuropathy and decreased neuronal‐derived nitric oxide); hormones (impaired testosterone release and actions); and metabolics (hyperlipidemia, advanced glycation end product formation).ConclusionBasic science evidence supports the link between ED and CVMD. The Committee also highlighted gaps in knowledge and provided recommendations for guiding further scientific study defining this risk relationship. This endeavor serves to develop novel strategic directions for therapeutic interventions. Musicki B, Bella AJ, Bivalacqua TJ, Davies KP, DiSanto ME, Gonzalez-Cadavid NF, Hannan JL, Kim NN, Podlasek CA, Wingard CJ, and Burnett AL. Basic science evidence for the link between erectile dysfunction and cardiometabolic dysfunction. J Sex Med 2015;12:2233–2255.     

A Mouse Model of Cavernous Nerve Injury-Induced Erectile Dysfunction: Functional and Morphological Characterization of the Corpus Cavernosum

IntroductionWith the advent of genetically engineered mice, it seems important to develop a mouse model of cavernous nerve injury (CNI).AimTo establish a mouse model of CNI induced either by nerve crushing or by neurectomy and to evaluate time-dependent derangements in penile hemodynamics in vivo and subsequent histologic alterations in the cavernous tissue.MethodsTwelve-week-old C57BL/6J mice were divided into 4 groups (N = 36 per group): control, sham operation, bilateral cavernous nerve crush, and bilateral cavernous neurectomy group.Main Outcome MeasuresThree days and 1, 2, 4, 8, and 12 weeks after CNI, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and TUNEL was performed. Immunohistochemical analysis was performed assaying for caspase-3, transforming growth factor-β1 (TGF-β1), phospho-Smad2, PECAM-1, factor VIII, and smooth muscle α-actin. The numbers of apoptotic cells and phospho-Smad2-immunopositive cells in endothelial cells or smooth muscle cells were counted.ResultsErectile function was significantly less in the cavernous nerve crushing and neurectomy groups than in the control or sham group. This difference was observed at the earliest time point assayed (day 3) and persisted up to 4 weeks after nerve crushing and to 12 weeks after neurectomy. The apoptotic index peaked at 1 or 2 weeks after CNI and decreased thereafter. Cavernous TGF-β1 and phospho-Smad expression was also increased after CNI. The numbers of apoptotic cells and phospho-Smad2-immunopositive cells in cavernous endothelial cells and smooth muscle cells were significantly greater in the cavernous nerve crush and cavernous neurectomy groups than in the control or sham group.ConclusionThe mouse is a useful model for studying pathophysiologic mechanisms involved in erectile dysfunction after CNI. Early intervention to prevent apoptosis in smooth muscle cells and endothelial cells or to inhibit cavernous tissue fibrosis is required to restore erectile function. Jin H-R, Chung YG, Kim WJ, Zhang LW, Piao S, Tuvshintur B, Yin GN, Shin SH, Tumurbaatar M, Han J-Y, Ryu J-K, and Suh J-K. A mouse model of cavernous nerve injury-induced erectile dysfunction: Functional and morphological characterization of the corpus cavernosum.     

Erectile Dysfunction Severity as a Risk Predictor for Coronary Artery Disease

IntroductionErectile dysfunction (ED) is now beginning to be considered as an early manifestation of a subclinical systemic vascular disorder and may be an index of subclinical coronary artery disease (CAD).AimTo further evaluate whether ED is a predicting factor for CAD while adjusting for other common risk factors.MethodsOne hundred eighty‐three patients with newly diagnosed and documented CAD and 134 participants without CAD were enrolled in this case‐control study at our referral center. Univariate and multivariate logistic regression analysis were performed to assess the effect of classic risk factors and ED severity on CAD; calculating odds ratio (OR) and 95% confidence interval (CI). Adjustments were made for potential confounding factors including age, hypertension, diabetes, dyslipidemia, obesity, and smoking.Main Outcome MeasuresThe prevalence of ED and the distribution of CAD risk factors (age, smoking, lipid profile, hypertension, obesity, and diabetes mellitus) were evaluated. The 5‐item International Index of Erectile Function was used to evaluate the presence and the severity of ED.ResultsThe prevalence of ED in CAD‐positive and CAD‐negative groups was 88.5% and 64.2%, respectively (P < 0.05). A statistically significant difference was found for all risk factors (except total cholesterol and low‐density lipoprotein levels), and also ED prevalence between studied groups. Adjusted OR for age, diabetes, hypertension, hypercholesterolemia, and smoking demonstrated a significant confounding effect. Our results also revealed a significant association between severe ED and CAD (OR: 2.22, 95% CI: 1.11–6.03; P < 0.05).ConclusionThis study suggests that ED could be considered as a surrogate marker which can predict the occurrence of CAD, and severe ED could be regarded as an independent risk predictor in addition to the established ones. Salem S, Abdi S, Mehrsai A, Saboury B, Saraji A, Shokohideh V, and Pourmand G. Erectile dysfunction severity as a risk predictor for coronary artery disease.     

The Predictive Value of Arteriogenic Erectile Dysfunction for Coronary Artery Disease in Men

Background

Erectile dysfunction (ED) is assumed to be connected with vascular disease caused by endothelial dysfunction, and characterized by the incapability of the smooth muscle cells lining the arterioles to relax, therefore, inhibit vasodilatation.

Uric Acid Level and Erectile Dysfunction in Patients with Coronary Artery Disease

IntroductionErectile dysfunction (ED) is a frequent complaint of elderly subjects and is closely associated with endothelial dysfunction and cardiovascular disease (CVD). Uric acid is also associated with endothelial dysfunction, oxidative stress, and CVD, raising the hypothesis that an increased serum uric acid might predict ED in patients who are at risk for coronary artery disease (CAD).AimThis study aims to evaluate the association of serum uric acid levels with presence and severity of ED in patients presenting with chest pain of presumed cardiac origin.MethodsThis is a cross-sectional study of 312 adult male patients with suspected CAD who underwent exercise stress test (EST) for workup of chest pain and completed a sexual health inventory for men survey form to determine the presence and severity of ED. Routine serum biochemistry (and uric acid levels) were measured. Logistic regression analysis was used to assess risk factors for ED.Main Outcome MeasuresThe short version of the International Index of Erectile Function questionnaire diagnosed ED (cutoff score ≤ 21). Serum uric acid levels were determined. Patients with chest pain of suspected cardiac origin underwent an EST.ResultsOne hundred forty-nine of 312 (47.7%) male subjects had ED by survey criteria. Patients with ED were older and had more frequent CAD, hypertension, diabetes and impaired renal function, and also had significantly higher levels of uric acid, fibrinogen, glucose, C-reactive protein, triglycerides compared with patients without ED. Uric acid levels were associated with ED by univariate analysis (odds ratio = 1.36, P = 0.002); however, this association was not observed in multivariate analysis adjusted for estimated glomerular filtration rate.ConclusionSubjects presenting with chest pain of presumed cardiac origin are more likely to have ED if they have elevated uric acid levels. Solak Y, Akilli H, Kayrak M, Aribas A, Gaipov A, Turk S, Perez-Pozo SE, Covic A, McFann K, Johnson RJ, and Kanbay M. Uric Acid level and erectile dysfunction in patients with coronary artery disease. J Sex Med 2014;11:165–172.     

Updated Evidence of Association Between Periodontal Disease and Incident Erectile Dysfunction

Introduction

The relationship between periodontal disease (PD) and erectile dysfunction (ED) is still conflicting.

Erectile Dysfunction,Penile Atherosclerosis,and Coronary Artery Vasculopathy in Heart Transplant Recipients

IntroductionVascular erectile dysfunction (ED) is the expression of a systemic vascular disease and in particular of endothelial dysfunction. Dysfunctional endothelium plays also a significant role in the onset and progression of coronary artery vasculopathy (CAV).AimThis pilot study was designed to evaluate the prevalence and pathogenesis of ED and its correlation with CAV in heart transplanted male.MethodsA total of 77 male heart transplanted patients (HTx) evaluated in our center (mean age 61.6 + 10.6 years) were enrolled in the study.Main Outcome MeasuresAll subjects underwent accurate medical history collection, including lifestyle (cigarette smoking, dietary and sedentary habits, drug intake, and erectile function before cardiac transplantation), physical examination (body mass index and arterial pressure), biochemical blood tests (fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides), and hormones (prolactin, luteinizing hormone and total testosterone). Furthermore, they were studied with penile, carotid, femoral echo-color Doppler ultrasonography and coronary angiogram.ResultsIncidence of ED was 24% before HTx and increased up to 65% after. Postischemic cardiomiopathy was an indication to HTx in ED group more frequently than in patients without ED (No-ED group) (45.1% vs. 20%). ED patients showed a lower peak systolic velocity, a higher cavernosal intima-media thickness (IMT), a higher prevalence of cavernosal plaques (26.7% vs. 5.2%, P < 0.05), peripheral vascular disease (60.87% vs. 26.1%, P < 0.05) and CAV (45.8% vs. 25.8%, P < 0.05) with respect to No-ED patients. Coronary flow reserve was significantly reduced in ED vs. No-ED patients (2.43 + 0.7 vs. 2.9 + 0.8, P < 0.04). Finally, cavernous plaque and testosterone plasma levels were statistically associated with CAV.ConclusionsWe showed that ED is a frequent disease in HTx patients, more common when the original pathology is postischemic cardiomiopathy and associated with higher prevalence of cavernous plaques and CAV. Its evaluation should be integral to an HTx rehab program. Caretta N, Feltrin G, Tarantini G, D'Agostino C, Tona F, Schipilliti M, Selice R, Minicuci N, Gerosa G, and Foresta C. Erectile dysfunction, penile atherosclerosis, and coronary artery vasculopathy in heart transplant recipients. J Sex Med 2013;10:2295–2302.     

Cavernous Artery Intima-Media Thickness: A New Parameter in the Diagnosis of Vascular Erectile Dysfunction

IntroductionA precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone.AimWe performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis.MethodsA total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study.Main Outcome MeasuresAll subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Δ-cavernous calliper]).ResultsCavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT.ConclusionsAn increased cavernous IMT (≥0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase. Caretta N, Palego P, Schipilliti M, Ferlin A, Di Mambro A, and Foresta C. Cavernous artery intima-media thickness: A new parameter in the diagnosis of vascular erectile dysfunction. J Sex Med **;**:**–**.     

Angiogenesis Therapy for the Treatment of Erectile Dysfunction

IntroductionOver the past 15 years, significant advances have been made in the treatment of erectile dysfunction (ED). The most significant of these advances has been pharmacological treatment of ED with phosphodiesterase type 5 (PDE5) inhibitors. This therapy greatly increased the awareness of ED and has helped stimulate research into the underlying causes of ED. While treatment with PDE5 inhibitors continues to be the current therapy of choice, approximately 40% of men treated with PDE5 inhibitors fail to have significant improvement in erectile function and PDE5 inhibitors do not reverse the vasculopathic processes associated with ED. With this in mind, new therapies must be developed. The treatment with angiogenic growth factors such as vascular endothelial cell growth factor (VEGF) may be one such therapy.AimThis review will focus on defining key terms in the angiogenic process, angiogenic growth factors, and different delivery methods, and summarize results from angiogenic therapies for the treatment of ED.MethodsA review of the literature was performed on all angiogenic therapies for the treatment of ED. A brief review on the angiogenic factors was also performedResultsAngiogenic therapies for the treatment of ED are possible and promising; however, further investigation is needed to advance clinically.ConclusionsAlthough numerous studies have now employed angiogenic factors for the possible treatment of ED in several animal models, we are still not at the point to begin human investigations. Future studies need to examine proper dosage of the angiogenic agent, route of delivery, time course for delivery, and combination therapies. Lysiak JJ, Kavoussi PK, Ellati RT, Steers WD, and Annex BH. Angiogenesis therapy for the treatment of erectile dysfunction.     

Enhanced Contribution of Orai Channels to Contractility of Human Penile Smooth Muscle in Erectile Dysfunction

BackgroundStore-operated calcium entry and its key players, stromal interaction molecule (STIM) and Orai calcium channels, have been proposed as emergent therapeutic targets in cardiovascular pathophysiology. We hypothesize alteration of STIM/Orai signaling in erectile dysfunction (ED).AimTo evaluate the contribution of STIM/Orai to human penile tissue contraction and to analyze the influence of ED on STIM/Orai signaling at functional and expression levels in human penile vascular tissues.MethodsHuman penile resistance arteries (HPRA) and human corpus cavernosum (HCC) were dissected from cavernosal specimens from 30 organ donors without history of ED (No ED) and from 48 patients with ED undergoing penile prosthesis insertion and functionally evaluated in wire myographs and organ chambers, respectively. Expression of STIM-1, Orai1, and Orai3 in HCC was localized and quantified by immunofluorescence.Main Outcome MeasuresThe main outcome measures are functional responses in HCC and HPRA and STIM/Orai channel protein expression in human cavernosal tissue.ResultsInhibition of Orai channels with YM-58483 (20 μM) significantly reduced norepinephrine–induced contractions in both HCC and HPRA from either No ED or ED subjects, but the effects were more marked in ED (−20.1 ± 5.9% vs −45.5 ± 13.2% and −15.9 ± 4.0% vs −31.4 ± 6.9% reduction in E_max to norepinephrine in HCC and HPRA, respectively). Thromboxane-induced contractions were reduced and neurogenic contractile and relaxant responses modulated by Orai inhibition in penile tissues from patients with ED. In fact, addition of YM-58483 concentration dependently relaxed precontracted HPRA and HCC. These relaxations were significantly more pronounced in tissues from patients with ED (EC₅₀ 7.5 vs 1.3 μM and 10.5 vs 1.3 μM, for HCC and HPRA, respectively). All HCC specimens displayed expression of STIM-1, Orai1, and Orai3. Significantly increased expression of Orai1 and Orai3 but not STIM-1 was observed in patients with ED.Clinical TranslationInhibition of enhanced Orai activity in human penile vascular tissue could facilitate erectile responses, alleviating ED.Strengths and LimitationsEnhanced STIM/Orai activity contribution to penile smooth muscle tone in ED is demonstrated at functional and structural levels in human tissues from a representative sample of patients with ED and in comparison with healthy tissue. We cannot differentiate the specific contribution of risk factors associated with ED to hyperactivity of the Orai system.ConclusionsOrai channels significantly contribute to human penile smooth muscle contraction. Orai contribution to penile smooth muscle tone is functionally enhanced in ED accompanied by increased expression of Orai channels in cavernosal tissue. Orai inhibition could be a potential therapeutic strategy to reduce penile smooth muscle contraction in ED.Sevilleja-Ortiz A, El Assar M, García-Rojo E, et al. Enhanced Contribution of Orai Channels to Contractility of Human Penile Smooth Muscle in Erectile Dysfunction. J Sex Med 2020;17:881–891.     

Erectile Dysfunction Precedes and Is Associated with Severity of Coronary Artery Disease among Asian Indians

IntroductionErectile dysfunction (ED) and coronary artery disease (CAD) often share common risk factors, and there is growing evidence that ED might serve as a clinical marker for cardiovascular disease. Despite rising trends of CAD in Asian Indians, limited data are available on the prevalence of ED and its correlation with CAD severity in such patients.AimTo study the prevalence of ED in Asian Indian patients undergoing coronary angiography and to assess if the severity of ED correlates with angiographic severity of CAD.MethodsIn all patients undergoing coronary angiography, ED was assessed using the International Index of Erectile Function‐5 questionnaire.Main Outcome Measures and ResultsAmong 175 male patients, ED was present in 70%; patients with ED had a higher incidence of multivessel CAD (80% vs. 36%, P 0.001), diffuse CAD (81% vs. 34%, P 0.001), and higher number of mean coronary vessels involved compared with those without ED. Those with severe ED had higher prevalence of multivessel CAD and higher number of mean coronary vessels involved compared with those with milder grades of ED. Onset of symptoms of ED preceded symptoms of CAD by a mean of 24.6 months in 84% of patients. The presence of severe ED was associated with a 21‐fold higher risk of having triple‐vessel disease (odds ratio [OR] 21.94, 95% confidence interval [CI] 3.41–141.09, P = 0.001) and an 18‐fold higher risk of having diffuse angiographic CAD (OR 17.91, 95% CI 3.11–111.09, P = 0.001).ConclusionAsian Indians with angiographic CAD frequently have ED; symptoms of ED precede that of CAD in most patients. Incidence of multivessel and diffuse CAD is significantly more common in patients with ED. It is important for physicians to be aware of the close relationship between the two conditions so that patients with ED can have optimal risk stratification for concomitant CAD whenever required.     

Penile Artery Shunt Syndrome: A Novel Cause of Erectile Dysfunction after Penile Revascularization Surgery

IntroductionPenile revascularization is a surgical treatment option for erectile dysfunction (ED) in healthy individuals due to a focal arterial occlusion in the absence of generalized vascular disease. Most described failures have been attributed to graft stenosis or disruption of the anastomosis.AimWe report a novel phenomenon called Penile Artery Shunt Syndrome that contributed to persistent ED in a patient after penile microvascular arterial bypass surgery.MethodsA 26‐year‐old man presented for evaluation of long‐standing ED, which was attributed to trauma sustained 12 years earlier. He had difficulty obtaining and maintaining erections despite oral pharmacotherapy. Clinical data related to the case were studied, analyzed, and reviewed with urologic and radiologic specialists at multiple centers that collaborated in the care of this patient.Main Outcome MeasuresPenile duplex ultrasound peak systolic velocities and five‐item International Index for Erectile Function questionnaire scores were the main outcome measures.ResultsInitial diagnostic workup of the patient confirmed severe insufficiency of the left cavernosal artery, with no evidence of venous leak. The patient underwent penile microvascular arterial bypass surgery with anastomosis of the left inferior epigastric artery to the left dorsal penile artery. The patient had persistence of severe ED despite patent anastomosis by penile duplex ultrasound. Subsequent arteriography revealed an arterial shunt due to an aberrant obturator artery arising from the donor inferior epigastric artery. The patient underwent embolization of the aberrant obturator artery, with resolution of the shunt and marked improvement in erectile function.ConclusionsThe presence of an aberrant obturator artery arising from the inferior epigastric artery may predispose to persistent ED after revascularization due to the creation of a shunt phenomenon. Pelvic arteriography may be useful in identifying anomalous anatomic considerations prior to penile revascularization and to evaluate patients with persistent postoperative ED. Pavlinec JG, Hakky TS, Yang C, Massis K, Munarriz R, and Carrion RE. Penile Artery Shunt Syndrome: A novel cause of erectile dysfunction after penile revascularization surgery. J Sex Med 2014;11:2338‐2341.     

Management of Erectile Dysfunction in General Practice

IntroductionIn recent years, the availability of effective oral pharmacological treatment for erectile dysfunction (ED) has revolutionized its management; however, it is still unclear how everyday clinical practice has changed in response to this evolving scenario.AimThe aim of this study is to describe general practitioners’ (GPs) beliefs and attitudes toward the management of ED.MethodsEach GP was asked to recruit consecutive men aged ≥18 years and sexually active, with already known erectile problems or with newly diagnosed ED.Main Outcomes MeasuresA written questionnaire was used to investigate GPs’ sociodemographic characteristics and their beliefs toward the management of ED.ResultsOverall, 127 GPs (53.4%) returned the questionnaire and 124 enrolled patients for the study. Only 9.5% of the GPs reported routinely inquiring about ED of patients >40 years of age, whereas 45.7% did it only when the patient raised the problem. GPs’ gender and age were associated with their beliefs about ED treatment and referral to specialist care. Overall, 932 patients were enrolled, of whom 38% had newly diagnosed ED. The problem came to light for initiative of patient in 80% of cases, and 84.8% of men were prescribed a treatment. Patients who on their own initiative discussed of their condition had an almost 3-fold increased probability to be treated than those whose GP began the discussion about ED (odds ratio [OR] = 2.6, confidence interval [CI] 95% 1.5–4.5). Patients followed by female physicians were significantly more likely to be referred to a specialist than those followed by male physicians (OR = 3.3, CI 95% 1.4–5.0).ConclusionsThe management of ED has become an integral component of clinical practice in primary care. Nevertheless, barriers in addressing sexual issues still persist. Appropriate training is needed for a proactive approach to ED screening and management in men over 40s. De Berardis G, Pellegrini F, Franciosi M, Pamparana F, Morelli P, Tognoni G, and Nicolucci A on behalf of the EDEN study group. Management of erectile dysfunction in general practice. J Sex Med **;**:**–**.     

Role of Nanotechnology in Erectile Dysfunction Treatment

IntroductionThe biological importance of nanotechnology-based delivery vehicles for in vivo tissue regeneration is gaining acceptance by the medical community; however, its relevance and incorporation into the treatment of sexual dysfunction are evolving and have not been well evaluated.AimTo provide scientific evidence examining the use of state-of-the-art nanotechnology-based delivery methodology in the treatment of erectile dysfunction (ED) in animal models and in patients.MethodsThis review assessed the current basic science literature examining the role of nanotechnology-based delivery vehicles in the development of potential ED therapies.ResultsThere are four primary areas where nanotechnology has been applied for ED treatment: (i) topical delivery of drugs for on-demand erectile function, (ii) injectable gels into the penis to prevent morphologic changes after prostatectomy, (iii) hydrogels to promote cavernous nerve regeneration or neuroprotection, and (iv) encapsulation of drugs to increase erectile function (primarily of phosphodiesterase type 5 inhibitors).ConclusionBasic science studies provide evidence for a significant and evolving role for nanotechnology in the development of therapies for ED and suggest that properly administered nano-based therapies might be advantageous for treating male sexual dysfunction.     

Prevalence and Risk Factors for Erectile Dysfunction in Chinese Adult Males

BackgroundThere is a lack of nationwide epidemiologic survey data on the prevalence estimate of erectile dysfunction (ED) in Chinese men living on the mainland China.AimTo attain the representative prevalence estimate of ED in the Chinese male population and to analyze potential risk factors associated with ED by demographics, socioeconomic status, and medical comorbidities.MethodsThe study was community based. The five-item Internation Index of Erectile Function questionnaire and in-person interview were used to obtain data. The survey subjects were 5,210 non-institutionalized Chinese men at least 40 years old residing in 30 provinces and autonomies of China. Multiple logistic regression analysis was used to disclose risk factors associated with ED.OutcomesThe prevalence estimate of ED was 40.56% in Chinese men at least 40 years old.ResultsThe prevalence of ED increased with increasing age. A significant high prevalence of ED was observed in men who smoked heavily, were estranged from a partner, had diabetes, and lower urinary tract symptoms from benign prostatic hyperplasia. Smoking more than 30 cigarettes daily and obesity (body mass index ≥ 30 kg/m²) significantly increased the risk for ED by multivariable-adjusted odds ratios. Stable or erratic sexual partners, personal incomes, alcohol consumption, and cardiovascular and/or cerebrovascular diseases were not risk factors associated with ED prevalence. Other sexual problems commonly seen in this group of men included difficulty achieving erectile rigidness, ejaculation, and climax during intercourse.Clinical TranslationKnowledge on the prevalence of ED and its associated risk factors will help physicians in the clinical management and prevention of ED with the use of counseling for lifestyle adjustment and drug therapy.Strengths and LimitationsData on the influence of psychological conditions on ED were not collected. ED was not categorized as minor, moderate, or severe for analysis during processing of data.ConclusionThe national representative prevalence of ED was determined for the first time in the Chinese male population.Zhang X, Yang B, Li N, Li H. Prevalence and Risk Factors for Erectile Dysfunction in Chinese Adult Males. J Sex Med 2017;14:1201–1208.     

Predictors of Erectile Function Normalization in Men With Erectile Dysfunction Treated With Placebo

Background

Clinical study and practice data have shown sildenafil improves sexual function in men with erectile dysfunction (ED). However, some men treated with placebo in double-blind, placebo-controlled sildenafil studies also report improved erectile function as measured by International Index of Erectile Function (IIEF)–Erectile Function Domain (EFD) scores.

Risk Factors for Erectile Dysfunction in Men With HTLV-1

BackgroundErectile dysfunction (ED) occurs in more than 50% of patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. In the general population, atherosclerosis is the main risk factor related to ED.AimTo compare the contribution of neurologic disorders from HTLV-1 with that of atherosclerosis as risk factors for ED in men with HTLV-1.MethodsIn this cross-sectional study, men 18 to 70 years old with HTLV-1 were classified into one of two groups according to the presence or absence of ED. They were compared for obesity, waist circumference, dyslipidemia, metabolic syndrome, diabetes mellitus, high blood pressure, and neurologic manifestations. Comparisons between proportions were performed using the χ² or Fisher exact test. Logistic regression analysis was performed to identify predictors of ED. Subjects with HTLV-1 were classified into three groups based on Osame's Disability Motor Scale and the Expanded Disability Status Scale: (i) HTLV-1 carriers; (ii) probable HTLV-1–associated myelopathy or tropical spastic paraparesis; and (iii) definitive HTLV-1–associated myelopathy or tropical spastic paraparesis. The International Index of Erectile Function was used to determine the degree of ED.ResultsIn univariate logistic regression, age older 60 years (P = .003), diabetes mellitus (P = .042), and neurologic disease (P < .001) were associated with ED. In the multivariate model, the odds of ED was highest in patients with neurologic disease (odds ratio = 22.1, 95% CI = 5.3–92.3), followed by high blood pressure (odds ratio = 6.3, 95% CI = 1.4-30.5) and age older than 60 years (odds ratio = 4.6, 95% CI = 1.3–17.3).Clinical ImplicationsIn men infected with HTLV-1, neurologic dysfunction is a stronger predictor of ED than risk factors for atherosclerosis.Strengths and LimitationsThe small number of patients limited the power of the statistical analysis, but clearly neurologic manifestations had a greater association with ED than risk factors for atherosclerosis, and there was no association between metabolic syndrome and severity of ED.ConclusionNeurologic impairment is the major cause of ED in individuals infected with HTLV-1 and risk factors for atherosclerosis did not have a strong relation with ED in this population.de Oliveira CJV, Neto JAC, Andrade RCP, et al. Risk Factors for Erectile Dysfunction in Men With HTLV-1. J Sex Med 2017;14:1195–1200.     

Metformin Treatment Improves Erectile Function in an Angiotensin II Model of Erectile Dysfunction

IntroductionIncreased angiotensin II (AngII) levels cause hypertension, which is a major risk factor for erectile dysfunction (ED). Studies have demonstrated that increased AngII levels in penile tissue are associated with ED. A recent study showed that metformin treatment restored nitric oxide synthase (NOS) protein expression in penile tissue in obese rats; however, whether metformin treatment can be beneficial and restore erectile function in a model of ED has not yet been established.AimThe goal of this study was to test the hypothesis that AngII induces ED by means of increased corpus cavernosum contraction, and that metformin treatment will reverse ED in AngII-treated rats.MethodsMale Sprague-Dawley rats were implanted with mini-osmotic pumps containing saline or AngII (70 ng/minute, 28 days). Animals were then treated with metformin or vehicle during the last week of AngII infusion.Main Outcome MeasuresIntracavernosal pressure; corpus cavernosum contraction and relaxation; nNOS protein expression; extracellular signal-regulated kinase (ERK1/2), AMP-activated protein kinase (AMPK), and eNOS protein expression and phosphorylation.ResultsAngII-induced ED was accompanied with an increase in corpus cavernosum contractility, decreased nitrergic relaxation, and increased ERK1/2 phosphorylation. Metformin treatment improved erectile function in the AngII-treated rats by reversing the increased contraction and decreased relaxation. Metformin treatment also resulted in an increase in eNOS phosphorylation at ser1177.ConclusionsMetformin treatment increased eNOS phosphorylation and improved erectile function in AngII hypertensive rats by reestablishing normal cavernosal smooth muscle tone. Labazi H, Wynne BM, Tostes R, and Webb RC. Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. J Sex Med 2013;10:2154–2164.