Erectile failure in the aged: evaluation and treatment

With aging, there are changes in both libido and erectile function. Although the majority of aged men remain interested in sex, less than 15% report continued sexual intercourse. The cause of this "libido-potency gap" is due primarily to erectile failure. Penile erection is dependent upon a complex interaction of the autonomic nervous system, cardiovascular system, and local neurotransmitters such as acetylcholine and vasoactive intestinal polypeptide. Sexual stimulation causes augmented blood flow into the corpora cavernosa, and restricted outflow, resulting in penile rigidity. With aging, there is a decline in gonadal steroids, nerve conduction velocity, and vascular compliance, any of which could interfere with normal erections. When disease is superimposed on the normal changes of aging, erectile function is further impaired. Evaluation of an elderly male with impotence may consist of a detailed drug history and trial of alternate therapy, as in the case of adverse drug reactions. More often, evaluation entails hormonal assays, penile vascular assessment, neurologic assessment, and an evaluation of nocturnal erectile function. Based on the results of these assessments, appropriate treatment alternatives can be chosen. With the availability of multiple treatment options, patients and physicians can now choose from a range of noninvasive or invasive alternatives depending upon the etiology, associated disorders, and preference of the patient.     

Quality of life following radical prostatectomy

Radical prostatectomy is a procedure performed with increasing frequency in patients with localized prostate cancer. Although, the operative morbidity is considerably low, urinary incontinence and erectile dysfunction remain an important and persistent problem. Since several years the impact of radical prostatectomy on the quality of life (HRQOL) is investigated. However, there are only few prospective studies dealing with rather small groups of patients. These studies indicate that urinary and sexual function have major impact on HRQOL. Although, there is a steady improvement in urinary function and decrease in urinary bother only about 65% of the patients reach the baseline at the end of the first year. In spite of this almost 90% of patients reach baseline in all other HRQOL domains such as general health perception, physical and social function after a mean period of 5 months. The importance of sexual desire and erectile capacity decreases with age; being important in 75 and 84% of men at the 5th decenium and 48 and 59% at the 6th decenium. After standard radical prostatectomy almost all of the patients are impotent. Applying so-called nerve sparing techniques erectile function may be preserved in careful selected patients. It is the common theme that preservation of the 'neurovascular bundles' equals a high rate, but still age depended postoperative potency; however difficulties in regaining urinary control may embarrass the patient to such an extent to withdraw from sexual activity. Furthermore, the change of sexual ability and quality may have impact on the partner who do not want to initiate sexual activity because of the possible failure. This may cause an increased level of emotional distance, which again is deleterious for sexual activities. Patients who are sexually active prior to surgery report major distress in case of postoperative erectile impotence, but even in case of maintained erectile capacity some patients are bothered by the sexual dysfunction. Sexual counselling and providing the optimal erectile aid is therefore very important. Psychological distress of spouses may be significantly greater than that of the patients; general cancer distress, treatment related worries, concerns on physical limitations and pain are the main reasons. However, it may well be that women are willing to report their problems more often than their partners who may have a grin-and-bear-it attitude. In spite of this caveate, it is important to include the patient's spouse into the discussions on therapy and associated morbidity early on. Since radical prostatectomy for localized prostate cancer is only one of the possible treatment options, the patient has to be informed about the incidence and various types of morbidity which is associated with treatment and their possible impact on HRQOL. Appropriate and honest counselling will have significant influence on the well being of the patient after completing therapy.     

增龄对大鼠阴茎勃起功能的影响

目的　探讨增龄在勃起功能障碍 ( ED)中的作用。方法　应用注射阿朴吗啡和电刺激海绵体神经的方法 ,观察低月龄大鼠与老龄大鼠阴茎勃起情况 ,采用免疫组化方法检测大鼠阴茎组织一氧化氮合酶 ( NOS)的染色情况。结果　注射阿朴吗啡后 ,老龄大鼠阴茎勃起次数要少于低月龄大鼠 ( P<0 .0 5) ;电刺激海绵体神经后 ,老龄组大鼠阴茎海绵体内压增幅与低月龄大鼠相近 ( P>0 .0 5) ,但勃起潜伏期延长 ( P<0 .0 5) ;组织化学染色显示低月龄大鼠阴茎组织 NOS的染色明显强于老龄大鼠。结论　增龄对大鼠阴茎勃起功能有一定的影响 ,主要表现在中枢调节及 NOS水平下降两方面     

Surgical management of erectile dysfunction

Since the introduction of sildenafil citrate, oral systemic therapy has become the first line of therapy for men with erectile dysfunction (ED). Men who are not candidates for or who fail treatment with an oral agent may choose second-line therapies such as intraurethral prostaglandins, penile injection therapy, sex therapy, or a vacuum erection device. These second-line therapies may be unpalatable or inadequate for some men, and these men constitute the candidates for surgical intervention for ED. This article reviews surgical management of vascular ED, surgical management of Peyronie’s disease, and penile prosthesis implantation. At the current time, the appropriate candidate for penile revascularization is a young man with proven arterial insufficiency resulting from pelvic trauma. Results in other populations are disappointing. Peyronie’s disease with curvature significant enough to interfere with intercourse may be managed with tunical lengthening or shortening procedures in potent men and with prosthetic implantation in men with ED. Modern three-piece penile prostheses are associated with excellent device reliability, high rates of patient satisfaction, and acceptably low complication rates.     

Management of erectile dysfunction in hypertension:Tips and tricks

Arterial hypertension is a major risk factor for cardiovascular disease and affects approximately one third of the adult population worldwide. The vascular origin of erectile dysfunction is now widely accepted in the vast majority of cases. Erectile dysfunction is frequently encountered in patients with arterial hypertension and greatly affects their quality of life of hypertensive patients and their sexual partners. Therefore, the management of erectile dysfunction in hypertensive patients is of paramount importance. Unfortunately, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients, mainly due to the lack of familiarity with this clinical entity by treating physicians. This review aims to discuss the more frequent problems in the management of hypertensive patients with erectile dysfunction and propose ways to overcome these problems in everyday clinical practice.     

Prolactinoma in a diabetic dialysis patient with erectile dysfunction: a difficult differential diagnosis

Dialysis patients often suffer from erectile dysfunction. The prevalence of this symptom in the context of dialysis is as high as 90%. Diabetes, diffuse vascular disease and pharmacological therapy are attendant causes of this condition, severely impairing the quality of life. Due to the high frequency of erectile dysfunction in uremic patients, minimalist diagnostic approaches are often used. Nevertheless, a careful differential diagnosis is also warranted in well dialyzed patients to identify causes and corrigible patterns. The case reported here exemplifies this critical issue. A 44 year old obese diabetic patient complained about the recent onset of erectile dysfunction. On examination, the penile echo-Doppler was normal, and suggested a cause other than dia-betic vascular disease. The high dialysis efficiency (daily hemodialysis, flexible schedules, EKRc from 15 to 25 ml/min) warranted the same diagnostic work-up as would adopted for non-uremic patients. Whilst the rising prolactine level (76.1 microg/l and 129 ng/ml) was still in the range commonly found in dialysis patients, a nuclear magnetic resonance examination was carried out and led to the identification of prolactinoma. Therapy with cabergoline was found effective and sexual potency was restored. Normalization of hormonal patterns followed within 2 months. This is the first case so far reported in a daily dialysis patient. It underlines the importance of a non-minimalist approach to the problem of sexual disorders in renal replacement therapy (RRT) patients, at least when dialysis efficiency is high and onset is rapid. It also suggests considering prolactinoma as an emerging diagnosis in the general population, which can be detected by the use of sensitive imaging techniques in the differential diagnosis of this condition.     

Sildenafil Citrate,a Selective Phosphodiesterase Type 5 Inhibitor:: Research and Clinical Implications in Erectile Dysfunction

Under normal physiological conditions, following sexual stimulation, release of nitric oxide (NO) from penile non-adrenergic, non-cholinergic nerves and the endothelium activates guanylyl cyclase and induces intracellular cGMP synthesis in erectile tissue trabecular smooth muscle cells. Increased cGMP levels reduce intracellular Ca²⁺ concentrations, inhibiting smooth muscle contractility and thereby initiating the erectile response. Phosphodiesterase type 5 (PDE type 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE type 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, resulting ultimately in restoration of basal smooth muscle contractility and penile flaccidity. Sildenafil citrate is a potent PDE type 5 reversible and selective inhibitor that blocks cGMP hydrolysis effectively (K_i ∼3 nM). Under conditions of excessive adrenergic tone or impaired neurovascular status, following sexual stimulation, sildenafil acts to enhance NO-mediated smooth muscle relaxation, resulting in improved penile erection in men with erectile dysfunction. In this review, we summarize the current state of knowledge of the physiology of penile erection and the pharmacology, metabolism and clinical experience with sildenafil citrate in the management of erectile dysfunction.     

All Men with Vasculogenic Erectile Dysfunction Require a Cardiovascular Workup

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction.     

Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection

Nitric oxide (NO) generated by neuronal NO synthase (nNOS) initiates penile erection, but has not been thought to participate in the sustained erection required for normal sexual performance. We now show that cAMP-dependent phosphorylation of nNOS mediates erectile physiology, including sustained erection. nNOS is phosphorylated by cAMP-dependent protein kinase (PKA) at serine(S)1412. Electrical stimulation of the penile innervation increases S1412 phosphorylation that is blocked by PKA inhibitors but not by PI3-kinase/Akt inhibitors. Stimulation of cAMP formation by forskolin also activates nNOS phosphorylation. Sustained penile erection elicited by either intracavernous forskolin injection, or augmented by forskolin during cavernous nerve electrical stimulation, is prevented by the NOS inhibitor l-NAME or in nNOS-deleted mice. Thus, nNOS mediates both initiation and maintenance of penile erection, implying unique approaches for treating erectile dysfunction.     

The erectile-endothelial dysfunction nexus: new opportunities for cardiovascular risk prevention

Erectile and endothelial dysfunction are common in individuals with multiple cardiovascular risk factors and are longitudinal predictors of cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction is intimately linked through increased expression and activation of endothelial nitric oxide synthase, and the subsequent physiological actions of nitric oxide. Endothelial production of nitric oxide by endothelial nitric oxide synthase in the corpus cavernosum is involved in the maintenance of penile erection. Erectile dysfunction can be detected clinically using systematic questioning and could potentially be employed as an independent predictor of cardiovascular risk to target treatment of cardiovascular risk factors. Both erectile and endothelial dysfunction respond to lifestyle modifications, particularly in individuals with the metabolic syndrome. Drugs that improve endothelial dysfunction can also improve erectile dysfunction, but responses are not always concordant. Phosphodiesterase type 5 inhibitors, however, are powerful agents that commonly improve erectile and endothelial dysfunction, with potential cardiac applications. The recent Princeton consensus requires more extensive implementation and evaluation in clinical practice. The judicious diagnosis of erectile dysfunction, nevertheless, provides a unique opportunity for the prevention of cardiovascular disease.     

Basis for the use of localized hypothermia during radical pelvic surgery

Controlled tissue cooling, or hypothermia, has been used therapeutically for decades to mitigate the negative effects of traumatic, ischemic, and surgical insults. When applied systemically, moderate hypothermia can attenuate or prevent the extent of neurologic sequelae. Localized hypothermia, on the other hand, has the capacity to reduce tissue edema, suppress inflammation, and minimize the severity of peripheral nerve injury. Therapeutic hypothermia has been used in critical care, neurosurgery, ophthalmology, otolaryngology, cardiothoracic surgery and most recently in urology. Nerve injury during radical pelvic surgery can result in urinary incontinence or retention, impotence and bowel dysfunction. Localized hypothermia during radical prostatectomy has demonstrated improved recovery of urinary continence and erectile function, and similar benefits might be observed in other types of radical pelvic surgery.     

Surgical treatment of Peyronie's disease

Peyronie's disease is a sexually debilitating disease causing significant penile deformity and erectile dysfunction as well as psychological stress for many men. The incidence of Peyronie's disease appears to be increasing and urologists are being called upon more frequently to treat this debilitating condition. Urologists have an opportunity to help men suffering from Peyronie's disease to improve their lives and the lives of their partners. Appropriate treatment should be individualized and tailored to the patient's expectations, disease history, physical exam findings, and coital function. After medical therapy is considered and the Peyronie's disease has stabilized, surgical correction is an excellent option for patients with functional impairment from their Peyronie's disease. Surgical outcomes are excellent with expected return to normal sexual function following Peyronie's disease treatment.     

Nocturnal Penile Tumescence Is Diminished but Not Ablated in Postproctectomy Impotence

PURPOSE: We aimed to assess objectively the integrity of the parasympathetic neural pathway that controls the inflow choke vessels to the corpora cavernosa in a group of male patients with postproctectomy erectile dysfunction. METHODS: The study group was male patients with erectile dysfunction after proctectomy for rectal cancer and inflammatory bowel disease identified by sexual function questionnaire. The group underwent two consecutive nights of home nocturnal penile tumescence monitoring with the Nocturnal Electrobioimpedance Volumetric Assessment device. The control group was also monitored. It comprised preoperative potent patients with rectal cancer and inflammatory bowel disease who had not yet undergone a variety of surgical procedures. Demographics and nocturnal penile tumescence parameters were recorded, including number, duration, and percentage increase in penile volume of tumescent events. RESULTS: Thirty-four impotent study group and 28 potent control group patients underwent nocturnal penile tumescence monitoring. The groups were well matched for mean age (difference, 1.4 years; 95 percent confidence interval, -5.8 to 8.6 years) and proportion with rectal cancer (difference, 6 percent; 95 percent confidence interval, -1 to 13 percent). The number of nocturnal penile tumescent events was greater for the potent group than for the control group (mean rank, 40.4 vs. 24.2; P = 0.0004). There was no significant difference between the mean duration (difference, 2.6 minutes; mean rank, 27.9 vs. 34.4; P = 0.16) or the mean penile volume increase (difference, 5.4 percent increase; mean rank, 30.6 vs. 32.6; P = 0.66) for tumescent events between the study and control groups. Mean age was significantly higher in complete than in partial impotence (60.9 vs. 53.1 years; difference, 7.8 years; 95 percent confidence interval, 0.1 to 15.5 years). There was a nonsignificant trend to a lower mean number of tumescence events among sildenafil responders than among nonresponders (3.5 vs. 4.8 events; mean rank, 11.2 vs. 17.3; P = 0.14). CONCLUSION: Nocturnal penile tumescence activity is diminished but not ablated by the trauma of surgical dissection. This suggests that some of the cavernous nerves that govern inflow to the corpora cavernosa are intact after surgery and that the nerve lesion responsible for erectile dysfunction is partial, and it explains why the response to sildenafil in such patients is surprisingly high.     

Erectile dysfunction and diabetes mellitus: mechanistic considerations from studies in experimental models

Diabetes is a major risk factor for erectile dysfunction. The condition degrades both neural and vascular endothelium penile control systems. Experimental and epidemiological evidence suggest that both hyperglycemia and dyslipidemia contribute to the etiology. These are the driving forces for elevated oxidative stress and the formation of advanced glycation and lipoxygenation end products, the major target being the nitric oxide systems of nerve and endothelium. This causes reversible functional loss followed by less reversible degenerative changes. These mechanisms have direct effects, such as the nitric oxide quenching, but perhaps more importantly, indirect effects on the regulation of nitric oxide synthase expression and activity, which can involve recruitment of proinflammatory cell signaling pathways. The latter include protein kinase C, mitogen-activated kinases, and the nuclear factor kappa B cascade. Diabetes also changes the trophic influences on nerve and endothelium. Together, these form potential therapeutic targets against diabetic erectile function, and indeed vascular disease in general.     

The Role of Nitric Oxide in Erectile Dysfunction: Implications for Medical Therapy

Erectile dysfunction is a common, multifactorial disorder that is associated with aging and a range of organic and psychogenic conditions, including hypertension, hypercholesterolemia, diabetes mellitus, cardiovascular disease, and depression. Penile erection is a complex process involving psychogenic and hormonal input, and a neurovascular nonadrenergic, noncholinergic mechanism. Nitric oxide (NO) is believed to be the main vasoactive nonadrenergic, noncholinergic neurotransmitter and chemical mediator of penile erection. Released by nerve and endothelial cells in the corpora cavernosa of the penis, NO activates soluble guanylyl cyclase, which increases 3',5'-cyclic guanosine monophosphate (cGMP) levels. Acting as a second messenger molecule, cGMP regulates the activity of calcium channels as well as intracellular contractile proteins that affect the relaxation of corpus cavernosum smooth muscle. Impaired NO bioactivity is a major pathogenic mechanism of erectile dysfunction. Treatment of erectile dysfunction often requires combinations of psychogenic and medical therapies, many of which have been only moderately successful in the past. The advent of oral phosphodiesterase type 5 (PDE-5) inhibitors, however, has greatly enhanced erectile dysfunction treatment; patients have demonstrated high tolerability and success rates for improved erectile function. The efficacy of the PDE-5 inhibitors also serves to illustrate the importance of the NO-cGMP pathway in erectile function since these agents counteract the degradation of NO-generated cGMP. Because not all patients respond to PDE-5 inhibitors, additional therapies are being investigated, such as soluble guanylyl cyclase activators and NO donors, which act on NO-independent and NO-dependent pathways, respectively.     

Clonidine suppresses copulatory behavior and erectile reflexes in male rats: lack of effect of naloxone pretreatment

Adrenergic transmitters and opioid peptides are implicated in the regulation of male sexual behavior. In the present studies we examine a possible interaction between these two neurochemical systems in the regulation of components of male sexual behavior. In mating tests, clonidine (0.25 mg/kg, 6 min pretest) induced a profound deficit in intromissive and ejaculatory behavior whereas naloxone (5 mg/kg, 20 min pretest) evinced a facilitation of ejaculatory behavior, evidenced by decreases in the ejaculation latency in the initial copulatory series and by decreases in ejaculation latency and intercopulatory interval in the second copulatory series. Importantly, prior treatment with naloxone did not prevent or attenuate the copulatory suppression induced by clonidine. In ex copula penile reflex tests, clonidine (0.25 mg/kg, 6 min pretest) decreased the incidence of seminal emission and the number of penile responses (erections, cups and flips). Naloxone (5 mg/kg, 20 min pretest) was without effect on any of the parameters of penile reflex activity and, further, failed to prevent or attenuate the erectile suppression induced by clonidine. A final study evaluated the dose-response relationship of clonidine-induced erectile dysfunction. A similar degree of erectile dysfunction was observed after 0.005, 0.025 or 0.25 mg/kg clonidine, whereas 0.0005 mg/kg was without effect. Previous studies demonstrated a dose-dependent inhibition of mounting, intromissive and ejaculatory behavior, with 0.25 mg/kg selectively eliminating ejaculatory behavior in mating tests. These data demonstrate a dose-dependent inhibition of penile reflexes, with inhibition occurring at doses lower than those required to induce copulatory dysfunction. Further, we suggest that opioid receptors sensitive to naloxone blockade are not involved in the clonidine-induced suppression of copulatory or erectile function.     

Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats

Apomorphine, a nonselective dopamine receptor agonist, facilitates penile erection and is effective in patients suffering from erectile dysfunction. The specific dopamine receptor subtype(s) responsible for its erectogenic effect is not known. Here we report that the dopamine D(4) receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D(4) receptor agonist that activates human dopamine D(4) receptors with an EC(50) of 12.4 nM and 61% efficacy, with no effect on dopamine D(1), D(2), D(3), or D(5) receptors. ABT-724 dose-dependently facilitates penile erection when given s.c. to conscious rats, an effect that is blocked by haloperidol and clozapine but not by domperidone. A proerectile effect is observed after intracerebroventricular but not intrathecal administration, suggesting a supraspinal site of action. s.c. injections of ABT-724 increase intracavernosal pressure in awake freely moving rats. In the presence of sildenafil, a potentiation of the proerectile effect of ABT-724 is observed in conscious rats. The ability of ABT-724 to facilitate penile erection together with the favorable side-effect profile indicates that ABT-724 could be useful for the treatment of erectile dysfunction.     

Finger and penile tactile sensitivity in sexually functional and dysfunctional diabetic men

Summary Tactile sensitivity of the penis is related to sexual functioning, however its role in diabetic erectile problems is unclear. We evaluated penile sensitivity in 10 diabetic men with erectile dysfunction, 17 sexually functional diabetic men and 14 control subjects. Finger and penile thresholds and ratings of intensity and pleasantness for finger and penis were assessed using vibrotactile stimulation. Glycosylated haemoglobin and total and bioavailable testosterone measurements were determined and subjects completed self-reports on sexual function. Diabetic men with erectile problems had higher values of glycosylated haemoglobin than sexually functional diabetic men (p = 0.02) and both groups had lower bioavailable testosterone than control subjects (p K 0.05). Sexually dysfunctional diabetic men had a higher finger threshold than the other two groups (p < 0.01). Penile threshold for the sexually dysfunctional group was also marginally higher compared with the functional diabetic group (p < 0.052) but did not differ from control subjects (p = 0.09). Diabetic men with erectile dysfunction exhibited different response patterns than sexually functional men on dimensions of intensity and pleasantness to penile stimulation. Although these data do not directly implicate subjective response to penile stimulation in diabetic erectile problems, they suggest such anomalous response could be one contributing factor. [Diabetologia (1999) 42: 336–342] Received: 28 April 1998 and in final revised form: 30 October 1998     

Several techniques proposed for the differential diagnosis of diabetic impotence

The measurements of changes in penile circumference during nocturnal erection is commonly used to differentiate between organic and psychogenic impotence. Unfortunately, this measuring technique do not record variations in penile rigidity which may be insufficient to achieve coitus despite a normal circumference. We carried out a study with a penile cuff to measure penile rigidity. The validation of this penile cuff as a measurement device of penile rigidity permits us to determine the criteria of normality of penile rigidity and, subsequently, to differentiate more accurately between organic and psychogenic dysfunctions. Measurement of the bulbocavernous reflex (BCR) is widely used to diagnose underlying neurologic disorders in erectile dysfunctions. A prolonged BCR latency, more than 45 ms, or absence of a reflex response of the BC muscles during electrical stimulation of the glans penis, is considered like a sign of neurologic disease. We recorded the BCR in 90 subjects. Nineteen had abnormal BCR latencies. Furthermore, eight of these 19 subjects had normal nocturnal erections, thus confirming the diagnosis of psychogenic impotence. These results cast doubt on the validity of BCR measurements of the diagnosis of organic erectile dysfunction due to a neurologic disease. We recorded the BCR in 90 subjects. Nineteen had abnormal BCR latencies. Furthermore, eight of these 19 subjects had normal nocturnal erections, thus confirming the diagnosis of psychogenic impotence. These results cast doubt on the validity of BCR measurements for the diagnosis of organic erectile dysfunction due to a neurologic disease.