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Erectile dysfunction and its pharmacology: An overview
Abstract
It has been estimated that currently over 150 million men worldwide suffer from erectile dysfunction (ED) and by 2025, the figure will increase beyond 322 millions. ED is the inability to achieve, and/or maintain penile erection sufficient for satisfactory sexual intercourse, and was previously regarded as the part of aging. It is associated with certain diseases and life style habits with a cause-effect relationship, including diabetes mellitus, hypertension, dyslipidemia, and cigarette smoking. Internationally, most of the men with ED fail to pursue treatment due to the complex nature of sexuality, taboos, cultural restrictions, and acceptance of ED as a normal sequel of aging. In this review, we discussed the physiology, diagnosis, and risk factors associated with ED and current treatment strategies for ED.
... Also, some researchers included iatrogenic endocrine disorders (amenorrhea, galactorrhoea and gynecomastia) as sexual dysfunction which is not termed under sexual dysfunction as per ICD-10, DSM-IV-TR, and therefore, may have affected the data on prevalence rates. Sexual dysfunction documented as antipsychotic-induced includes, decrease libido, erectile dysfunction, delay orgasm, anorgasmia, and ejaculation disorders (delayed or inhibited ejaculation, retrograde ejaculation, spontaneous ejaculation in the absence of sexual stimulation, decreased ejaculatory volume) [23][24][25]. In our study, the prevalence of sexual dysfunction with risperidone and haloperidol is 12.5 % each; decreased libido and premature ejaculation were found to be associated with them. ...
Objective: To assess the role of clinical pharmacists in the identification and management of drug-induced sexual dysfunction in collaboration with the psychiatrist and also to determine the prevalence and pattern of drug-induced sexual dysfunction, identify nature and extend of drug-induced sexual dysfunction, and assess the pattern of management of drug-induced sexual dysfunction. Methods: This periodic prevalence interventional study was carried out among patients who visited the psychiatric department of a university hospital over three month’s period. Patients were screened for sexual dysfunction using the Arizona Sexual Experience Scale (ASEX) by study pharmacists. Results: Of the 100 patients reviewed, only 50% of subjects met the study criteria. Depression (42%) was the most common clinical diagnosis among the study patients. The overall prevalence of drug-induced sexual dysfunction was 16%. A higher incidence of drug-induced sexual dysfunction was observed in men (62.5%). Decrease libido (40%) was the most prominently observed drug-induced sexual dysfunction in both genders. Antidepressant (50%) was the most common class of drugs implicated in sexual dysfunction. Drug-induced sexual dysfunction was pharmacologically managed with vaginal lubrication (40%), Tadalafil (20%) and Tadalafil+Dapoxetine combination (40%). Conclusion: With this study, provided a vision, further how prospective studies in this arena may be carried out for better understanding drug-induced sexual dysfunction and how a clinical pharmacist can contribute for better health care of patients in the sex clinic by collaborating with medical practitioners.
... Sildenafil is the first-line oral therapy that is effective for the treatment of ED. Though effective in circumventing the cause of ED, oral sildenafil therapy provides only short-term symptomatic relief of the condition [17]. The Asian MALES study has revealed that a majority or near majority of Asian men with self-reported ED have never sought treatment [18]. ...
Objective: This systematic review was conducted to summarize and evaluate the effect of Eurycoma longifolia (EL) on sexual behavior in the sexually dysfunctional male.Methods: Ovid Medline, Wiley Online Library, Scopus, BioMed Central, Hindawi and Google Scholar databases were searched for relevant studies published from 1995 to 2016 and search was limited to relevant studies published in English. Studies assessing aphrodisiac properties of EL on male sexual behavior in sexually dysfunctional animal models or human were included.Results: Among the 155 studies identified in the literature search, a total of 6 eligible articles (5 animal studies and one human study) were selected and reviewed. All studies reported positive aphrodisiac activities and supported the use of the plant as an aphrodisiac.Conclusion: This systematic review highlighted the effect of EL extract as an aphrodisiac agent to improve sexual behavior in the sexually dysfunctional male. Further studies are required to determine the specific mechanisms of action and identification of the bioactive components of EL responsible for its potential efficacy.
Diabetes would not just have a high blood glucose level in the individual body, yet these days diabetes likewise goes with numerous other organic issues like hypertension, feeble the myocardial layer working, sexual broke, and so on. These are some real issue which is these days joined by diabetes to a person’s body. Guys are for the most part being determined to have the sexual broke issue, guys, as well as experience a sexual broke issue. As similarly we may see less clinical examinations, including sexual broke issues looked for the sort two diabetic ladies. The primary goal of this article is to illuminate the situation that females proceed with much trouble with regards to the sexual broke Complication that might be physiological or neurotic if there should arise an occurrence of sorting two diabetes in ladies. It chiefly involves the useful extent of females like sexual drive, excitement, vaginal grease, Orgasm and general fulfilment space. Talking about the treatmentaccess of the ailment in the analyti way for it, Diabetes essentially hinders the sexual execution of Diabetic Women. Determinants of sexual ability incorporate age and extent of diabetes.
Phosphodiesterase (PDE) inhibitors are important therapeutic agents, but their effects on photoreceptor PDE (PDE6) and photoreceptor cells are poorly understood. The potency and selectivity of various classes of PDE inhibitors on purified rod and cone PDE6 and on intact rod outer segments (ROS) were characterized.
The inhibition constant (K(i)) of isozyme-selective PDE inhibitors was determined for purified rod and cone PDE6. Perturbations of cGMP levels in isolated ROS suspensions by PDE inhibitors were quantitated by a cGMP enzyme-linked immunoassay.
Most PDE5-selective inhibitors were excellent PDE6 inhibitors. Vardenafil, a potent PDE5 inhibitor (K(i) = 0.2 nM), was the most potent PDE6 inhibitor tested (K(i) = 0.7 nM). Zaprinast was the only drug that inhibited PDE6 more potently than did PDE5. PDE1-selective inhibitors were equally effective in inhibiting PDE6. In intact ROS, PDE inhibitors elevated cGMP levels, but none fully inhibited PDE6. Their potency for elevating cGMP levels in ROS was much lower than their ability to inhibit the purified enzyme. Competition between PDE5/6-selective drugs and the inhibitory gamma-subunit for the active site of PDE6 is proposed to reduce the effectiveness of drugs at the enzyme-active site.
Several classes of PDE inhibitors inhibit PDE6 equally as well as the PDE family to which they are targeted. In intact ROS, high PDE6 concentrations, binding of the gamma-subunit to the active site, and calcium feedback mechanisms attenuate the effectiveness of PDE inhibitors to inhibit PDE6 and disrupt the cGMP signaling pathway during visual transduction.
Objective: A gas chromatography (GC) method using flame ionization (FID) and mass spectrometry (MS) was developed and validated for the determination of nine local anaesthetics in counterfeit drugs sold illegally as treatments for male premature ejaculation. Methods: The GC-FID and GC-MS method validations demonstrated reliable specificity, selectivity, linearity, precision, and accuracy, and the validated methods were successfully applied to the analyses of collected samples. Results: Approximately 60% of the samples contained, at least, one of the local anaesthetics, which included menthol, 2-phenoxyethanol, eugenol, lidocaine, prilocaine, and tetracaine. Lidocaine was the most frequently detected compound in the analysed samples and occurred in a wide concentration range (2.81–52.40 mg/g). The concentrations of the detected compounds varied greatly between 0.03–52.40 mg/g. Conclusion: Continuous use of these counterfeit products, which contain high concentrations of local anaesthetics, can cause serious human health effects. Therefore, the continued screening of illegal products is required and our proposed methods could be used for the monitoring and quantification of local anaesthetics in counterfeit products.
Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance. Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 μg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days. Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level. Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP. © 2015, International Journal of Pharmacy and Pharmaceutical Science. All right resurved.
The effects of Eurycoma longifolia JACK were studied on the orientation activities of sexually experienced male rats towards receptive females (mounting, licking, anogenital sniffing), environment (exploration, raring, climbing), themselves (genital grooming, non-genital grooming) and mobility (unrestricted, restricted) after dosing them with 200, 400 and 800 mg/kg body weight twice daily for 10 d prior to the test. The results showed that E. longifolia JACK modified the orientation activities of the treated male rats in that they significantly displayed more frequent and vigorous mounting, licking and anogenital sniffing towards the receptive females, and it further intensified self orientation as indicated by the increased grooming of the genitals compared to the controls (p<0.05). In addition, rats treated with 800 mg/kg of methanol, water and butanol extracts of E. longifolia JACK continued to show confinement to a particular area of the cage (around the female), thus showing restriction in movement as compared to the controls (p<0.05). However, the treated males possessed a lack of interest in the external environment as indicated by a reduction in exploration, raring and climbing on the cage wall. Hence, the present study further supports the folk use of E. longifolia JACK as an aphrodisiac.
The sexual dysfunctions are extremely common but are rarely recognized by primary care physicians. They represent inhibitions in the appetitive or psychophysiologic changes that characterize the complete adult sexual response and are classified into four major categories: (1) sexual desire disorders (hypoactive sexual desire, sexual aversion disorder), (2) sexual arousal disorders (female sexual arousal disorder, male erectile dysfunction), (3) orgasmic disorders (inhibited male or female orgasm, premature ejaculation), and (4) sexual pain disorders (dyspareunia, vaginismus).
Articles about the sexual dysfunctions were obtained from a search of MEDLINE files from 1966 to the present using the categories as key words, along with the general key word "sexual dysfunction." Additional articles came from the reference lists of dysfunction-specific reviews.
Cause and pathogenesis span a continuum from organic to psychogenic and most often include a mosaic of factors. Organic factors include chronic illness, pregnancy, pharmacologic agents, endocrine alterations, and a host of other medical, surgical, and traumatic factors. Psychogenic factors include an array of individual factors (e.g., depression, anxiety, fear, frustration, guilt hypochondria, intrapsychic conflict), interpersonal and relationship factors (e.g., poor communication, relationship conflict, diminished trust, fear of intimacy, poor relationship models, family system conflict), psychosexual factors (e.g., negative learning and attitudes, performance anxiety, prior sexual trauma, restrictive religiosity, intellectual defenses), and sexual enactment factors (e.g., skill and knowledge deficits, unrealistic performance expectations). Understanding the cause and pathophysiology of sexual disorders will help primary care physicians diagnose these problems accurately and manage them effectively.
The localization, synthesis, and activity of endothelin and the receptor types mediating its effects in penile corpus cavernosum were investigated in whole tissue and in cultured cells derived from this tissue. With immunocytochemistry, utilizing an antiendothelin 1 (ET-1) monoclonal antibody, endothelin-like immunoreactivity was localized intensely in the endothelium and to a lesser degree in the trabecular smooth muscle. Human corpus cavernosum endothelial cells in culture expressed preproendothelin 1 mRNA, as determined by Northern blot analysis. Significant amounts of endothelin-like immunoreactivity were measured by radioimmunoassay in the supernatants of corpus cavernosum endothelial cells in culture. Endothelins are potent constrictors and caused long-lasting contractions of corporeal strips in organ chambers. Equilibrium binding analysis of endothelins to their receptor sites revealed high-affinity, specific, and saturable binding of labeled endothelins to corporeal membranes. Competition binding experiments demonstrated receptors with high affinity for ET-1 and -2 and low affinity for ET-3 and another, less abundant, set of receptors with high affinity for ET-1, -2, and -3. Affinity labeling of endothelins to corporeal membranes, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, revealed that ET-1 and -2 cross-linked specifically to three different molecular mass components (75, 52, and 34 kDa). ET-3 bound only to the 34-kDa component. It is concluded that human corpus cavernosum endothelium has the ability to synthesize and release endothelin, that endothelins contract corporeal smooth muscle, and that at least two distinct endothelin receptors may exist and are differentiated by their affinity for ET-3.
When it results from depressive illness, sexual dysfunction may improve as the patient responds to antidepressant therapy. However, many antidepressants can cause sexual side effects including loss of libido, lack of orgasm, erectile disturbances, and inhibition of ejaculation. These side effects from antidepressants are reversible, usually respond to a reduction in dosage, and should be the focus of physician-patient communication to prevent noncompliance with therapy. The types and mechanisms of sexual side effects from antidepressants are presented.
We provide current, normative data on the prevalence of impotence, and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study. The Massachusetts Male Aging Study was a community based, random sample observational survey of noninstitutionalized men 40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston, Massachusetts. Blood samples, physiological measures, socio-demographic variables, psychological indexes, and information on health status, medications, smoking and lifestyle were collected by trained interviewers in the subject's home. A self-administered sexual activity questionnaire was used to characterize erectile potency. The combined prevalence of minimal, moderate and complete impotence was 52%. The prevalence of complete impotence tripled from 5 to 15% between subject ages 40 and 70 years. Subject age was the variable most strongly associated with impotence. After adjustment for age, a higher probability of impotence was directly correlated with heart disease, hypertension, diabetes, associated medications, and indexes of anger and depression, and inversely correlated with serum dehydroepiandrosterone, high density lipoprotein cholesterol and an index of dominant personality. Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension. We conclude that impotence is a major health concern in light of the high prevalence, is strongly associated with age, has multiple determinants, including some risk factors for vascular disease, and may be due partly to modifiable para-aging phenomena.
From November 1985 to April 1990, 216 consecutive patients were treated with the vacuum constriction device. Patients were mailed an initial questionnaire (group 1) and a long-term questionnaire (group 2) at a median followup of 3 and 29 months, respectively. Of 202 available patients 161 in group 1 (75%) and 115 in group 2 (57%) responded. Regular use of the vacuum constriction device was reported by 69% group 1 and 70% group 2 patients. patient and partner satisfaction was 82% and 87% in group 1, and 84% and 89% in group 2, respectively. There were no significant differences between the groups with respect to regular use and patient or partner satisfaction (p < 0.05). Quality of erection was evaluated for hardness, length and circumference, and with satisfaction greater than 90% in both groups. Median times per month of successful intercourse were 1, 4 and 4 for the year before, during and after obtaining the vacuum constriction device in group 2. Also, 79% of the patients in group 2 reported a statistically significant increase in the frequency of intercourse per month in the first year, which was sustained beyond the first year in 77% (p < 0.01). Our results support the efficacy of the vacuum constriction device for the treatment of impotence. Overall regular use rates as well as patient and partner satisfaction appear to be high. Furthermore, excellent initial results appear durable in most patients.
We assessed patient preference, satisfaction and overall outcome of goal directed management of erectile dysfunction.
The results of goal directed therapy of impotence were assessed by an independent telephone survey of 377 consecutive men who had not received prior therapy and who were followed for a minimum of 2 years.
Patients preferred medical to surgical therapies despite significantly higher satisfaction rates achieved with surgery. Average number of treatment modalities chosen by each patient was 2 (range 0 to 5). Ultimately, only 40% of the patients achieved a long-term satisfactory result with goal directed therapy. The remainder were not satisfied with the last treatment but chose no further therapy, were lost to followup or refused therapy from the outset.
Our results clearly demonstrate a patient preference for the least invasive forms of therapy. Patients avoid significantly more effective but also more invasive treatment options despite unsatisfactory results with less invasive methods. Future research efforts should be concentrated on the development of new medical therapies to enhance overall patient satisfaction.
To investigate the efficacy in treating erectile dysfunction and to develop a natural drug without complications, the results of ginseng treatments are compared to placebo and other drug. A total of 90 patients with 30 patients in each group were closely followed. Changes in symptoms such as frequency of intercourse, premature ejaculation, and morning erections after treatment were not changed in all three groups (p > 0.05). However in the group receiving ginseng, changes in early detumescence and erectile parameters such as penile rigidity and girth, libido and patient satisfactions were significantly higher than that of other groups (p < 0.05). The overall therapeutic efficacies on erectile dysfunction were 60% for ginseng group and 30% for placebo and trazodone treated groups, statistically confirming the effect of ginseng (p < 0.05). No complete remission of erectile dysfunction was noted, but partial responses were reported. No cases of aggravation of symptoms were reported. AVS-penogram, which is a recording of penile hemodynamic changes during the natural erection after audiovisual erotic stimulation, is not changed after administration of ginseng. However if administered for a prolonged period of time, the cummulative effect on vascular flow might be seen. The administration of Korean red ginseng has shown to have superior effects compared to the placebo or trazodone. Definitely more researches are required to elucidate the mechanism of ginseng. The effects of saponin, extracted from ginseng, on smooth muscle of erectile tissues, can be evaluated using organ chamber or nitric oxide titration, thereby pinpointing the exact action mechanism of saponin. As more informations are available, possible breakthrough in treatment of erectile dysfunction could be arisen from active saponin extracted from red ginseng, bringing hopes to many sufferers of erectile dysfunction.
Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder.
Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 microg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home.
During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P<0.001). On average, 7 of 10 alprostadil administrations were followed by intercourse in men responsive to treatment. The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo). The most common side effect was mild penile pain, which occurred after 10.8 percent of alprostadil treatments, but the pain rarely resulted in refusal to continue in the study. Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil. Hypotension-related symptoms were uncommon at home. No men had priapism or penile fibrosis.
In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.
Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder.
This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration.
Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study.
Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.
A study comparing intracorporeal injection of prostaglandin E1 (one-drug solution) and papaverine plus prostaglandin E1 (2-drug solution) for treatment of impotence.
A total of 100 impotent patients had intracorporeal injections of the one-drug and 2-drug solution alternatively in 3 sessions. The quality and duration of erections were assessed.
Seventy-five per cent of the patients developed full erection with the 2-drug solution compared to 50% with the one-drug solution. The average duration of erections was 60 minutes and 45 minutes, respectively. The complication rate was higher for the 2-drug solution.
Papaverine plus prostaglandin E1 is superior to prostaglandin E1 alone for treatment of impotence, but has a higher rate of complications. Intracavemous injection of vasoactive drugs is a very effective and important way for treatment of impotence. Papaverine plus prostaglandin E1 had been used for treatment of impotence alone or combined. A blind study was done to compare efficiency and complication rates of intracavemous injection of papaverine plus prostaglandin E1 (2-drug solution) with prostaglandin E1 alone.
The erect penis has always been a symbol of power, virility, and fertility. Inability to obtain or maintain an erection, known clinically as erectile dysfunction, is a major health problem. It can cause considerable distress, unhappiness, and relationship problems. The search has therefore continued from time immemorial to find an effective safe, and easy to administer treatment for erectile problems. Although a number of these treatments became available in the last two decades, they all had problems with efficacy, safety, or ease of administration. Clinicians in this field often are told at the end of an assessment interview, "I wish you have a magic pill". An effective and safe oral treatment is, no doubt, the most acceptable and easy to use option. Finding such a treatment has always been the dream of many scientists, and many attempts have been made over the years. These ranged from herbal remedies used by native healers, mostly in Eastern countries, to the more sophisticated designer drugs, which are based on a better understanding of the physiological mechanism of erection. This article describes some of these attempts.
Erectile dysfunction is a common problem, particularly in diabetics. It is associated with a considerable burden of suffering. No generally accepted drug treatment exists. We systematically reviewed and meta-analyzed all randomized, placebo controlled trials of yohimbine monotherapy for erectile dysfunction to determine its therapeutic efficacy. Our secondary aim was to evaluate the safety of yohimbine.
We used computerized literature searches and standardized data extraction to rate methodological quality in a meta-analysis using computer statistical software.
Seven trials fit the predefined inclusion criteria. Overall methodological quality of these studies was satisfactory. The meta-analysis demonstrated that yohimbine is superior to placebo in the treatment of erectile dysfunction (odds ratio 3.85, 95% confidence interval 6.67 to 2.22). Serious adverse reactions were infrequent and reversible.
The benefit of yohimbine medication for erectile dysfunction seems to outweigh its risks. Therefore, yohimbine is believed to be a reasonable therapeutic option for erectile dysfunction that should be considered as initial pharmacological intervention.
To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe.
In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug.
A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis.
Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.
Studies have shown that there is an association between depression and male erectile dysfunction (MED). However. these earlier studies suffer considerable methodological flaws including: a) lack of a multidisciplinary approach; b) poor sampling techniques; and finally, c) poor and variable measures of MED and depression. Our objectives are: a) to determine whether MED is associated with depressive symptoms and b) to determine whether this association is independent of aging and para-aging factors.
Data were obtained from the Massachusetts Male Aging Study (MMAS). The MMAS was a cross-sectional, population-based multidisciplinary survey of health in normally aging men (aged 40-70 years) conducted from 1986 to 1989. In the analytic model, depressive symptoms, as measured by a score of 16 or greater on the Center for Epidemiological Studies-Depression (CES-D) scale, was used as a predictor of MED, which was assessed with a self-administered questionnaire.
MED was associated with depressive symptoms after controlling for potential confounders (odds ratio (OR) 1.82, 95% confidence interval (Ct) 1.21-2.73).
We conclude that the relationship between depressive symptoms and MED in middle-aged men is robust and independent of important aging and para-aging confounders, such as demographic, anthropometric and lifestyle factors, health status, medication use, and hormones.
Erectile dysfunction (ED) is the most common sexual problem in men, after premature ejaculation, affecting up to 30 million in the United States. In a society in which sexuality is widely promoted, ED impacts on feelings of self-worth and self-confidence and may impair the quality of life of affected men and their partners. Damage to personal relationships can ensue; and the anger, depression, and anxiety engendered spill over into all aspects of life. Patients are often embarrassed or reluctant to discuss the matter with their primary care practitioners. Unfortunately, many physicians fail to take the opportunity to promote open discussion of sexual dysfunction. They too, may avoid the topic through personal embarrassment. Since the National Institutes of Health (NIH) Consensus Conference on Impotence in 1992, the inadequate level of public and professional understanding of ED has begun to be addressed. As a first step in breaking down the communication barriers between patients and practitioners, it is important that physicians have a thorough understanding of the wide variety of conditions associated with ED and how the different risk factors for ED may be readily identified. This review addresses the diagnosis of ED and identifies diagnostic tests that can be used by primary care physicians to determine the patients most at risk and the treatments most suited to meet the patients' and their partners' goal for therapy.
To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI).
Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schramek's grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schramek's grading.
The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy.
MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patient's level of satisfaction with the quality of the erection compared with intracavernosal injections.
Published studies on the epidemiology of erectile dysfunction and the physiology/ pathophysiology of erectile function are reviewed.
A literature search of more than 400 studies of the epidemiology and pathophysiology of impotence and erectile dysfunction published during the last 3 decades was conducted and the most pertinent articles are discussed.
It has been estimated that the prevalence of erectile dysfunction of all degrees is 52% in men 40 to 70 years old, with higher rates in those older than 70 years. Erectile dysfunction has a significant negative impact on quality of life. Risk factors for erectile dysfunction include aging, chronic illnesses, various medications and cigarette smoking. A nitric oxide/cyclic guanosine monophosphate mechanism has an important role in mediating the corporal smooth muscle relaxation necessary for erectile function. Other mechanisms involving neuropeptides, gap junctions and ion channels also may modulate corporal smooth muscle tone. Erectile dysfunction can be due to vasculogenic, neurogenic, hormonal and/or psychogenic factors as well as alterations in the nitric oxide/cyclic guanosine monophosphate pathway or other regulatory mechanisms, resulting in an imbalance in corporal smooth muscle contraction and relaxation.
Erectile dysfunction is a common condition associated with aging, chronic illnesses and various modifiable risk factors. Normal penile erection is a hemodynamic process that is dependent on corporal smooth muscle relaxation mediated by parasympathetic neurotransmission, nitric oxide, and possibly other regulatory factors and electrophysiological events. As more knowledge is gained of the physiology and regulatory factors that mediate normal erectile function, the mechanisms involved in the pathophysiology of erectile dysfunction should be further elucidated.
It is important to realise that virtually every part of the body, including the urological system, is adversely affected by smoking. Smoking is the most important known preventable cause of urinary bladder cancer and is also associated with a risk of prostatic and renal cancer. The exact mechanism by which smoking increases the incidence of urological malignancy is not known. One possibility is that chemicals in cigarette smoke inhibit the synthesis of cytoprotective eicosanoids. Deficient local protection, against the hostile environment caused by the presence of urine, could then encourage the process of carcinogenesis. Smoking is a powerful predictor of erectile dysfunction; cessation may restore normal function. Cigarette smoke also exerts adverse effects on sperm motility and count. Although there is no convincing evidence of reduced fertility in male smokers, it is advisable for men to quit smoking should they have marginal semen quality and wish to start a family. Smoking causes substantial urological pathology; these facts can be used to convince patients with urological problems to quit smoking.
In 1994, the Massachusetts Male Aging Study presented an inverse correlation of the serum levels of dehydroepiandrosterone (DHEA) and the incidence of erectile dysfunction (ED). We evaluated the efficacy of DHEA replacement in the treatment of ED in a prospective, double-blind, randomized, placebo-controlled study.
The inclusion criteria included ED, normal physical and neurologic examinations, serum levels of testosterone, dihydrotestosterone, prolactin, and prostate-specific antigen (PSA) within the normal range, and a serum DHEA sulfate level below 1.5 micromol/L. Also all patients had a full erection after a pharmacologic erection test with 10O microg prostaglandin E1; pharmacocavernosography showed no visualization in corporeal venous structures. Forty patients from our impotence clinic were recruited and randomly divided into two groups of 20 patients each. Group 1 was treated with an oral dose of 50 mg DHEA and group 2 with a placebo one time a day for 6 months. The International Index of Erectile Function (IIEF), a 15-item questionnaire, was used to rate the success of this therapy.
Therapy response was defined as the ability to achieve or maintain an erection sufficient for satisfactory sexual performance according to the National Institutes of Health Consensus Development Panel on Impotence. DHEA treatment was associated with higher mean scores for all five domains of the IIEF. There was no impact of DHEA treatment on the mean serum levels of PSA, prolactin, testosterone, the mean prostate volume, and the mean postvoid residual urine volume.
Our results suggest that oral DHEA treatment may be of benefit in the treatment of ED. Although our patient data base is too small to do relevant statistical analysis, we believe that our data show a biologically obvious trend that justifies further extended studies.
We conducted a study to evaluate the impact of obesity on erectile function in men with erectile dysfunction.
Three hundred and twenty-five consecutive patients with erectile dysfunction were evaluated. We classified the men into 2 groups according to body weight: <120% of the ideal body weight, and >/=120%. We compared several erectile capacities and the findings of penile duplex ultrasonography.
There was a statistically significant decrease in the quality of residual erectile function in patients with obesity (penile rigidity grade 1.32 versus 1.62 in the nonobese patients). Obese patients also have an increased prevalence of vascular risk factors based on a review of the medical records and vascular impairment by duplex ultrasound study (43 and 62% in the obese patients versus 30 and 42% in the nonobese patients, respectively, p < 0.05). However, when we focused only on the patients without any vascular risk factors, no significant difference between the 2 groups was noted in the quality of residual erectile function and also the prevalence of penile vascular impairments (p > 0.05).
These data demonstrate that obesity in itself does not seem to be an underlying factor, but does impose a risk to vasculogenic impotence by developing chronic vascular disease.
The aim of this study was to assess the longterm mechanical reliability of AMS (American Medical Systems) three-piece inflatable implants and their impact on patient-partner satisfaction in 200 consecutive patients with erectile dysfunction who underwent surgery in five different institutions.
Patient charts included in the study were collected and extensively assessed to record pre- and intraoperative data and postoperative complications. All patients and 120 partners were then seen often in the office at a mean follow-up of 59 months (range 6-130) and they were extensively questioned about function of the device and its impact on the couple's sexual life.
At the long-term follow-up, 185 patients (92.5%) were still engaging in sexual intercourse with a mean frequency of 1.7/week. Patients and partners reported prosthetic erections as excellent, satisfactory or poor in 96 (48%), 100 (50%) and 4 (2%) cases, and in 20 (17%), 80 (66%) and 20 (17%) cases, respectively. Postoperative sexual activity was considered excellent, satisfactory or poor by 140 (70%), 44 (22%) and 16 (8%) patients and by 34 (28%), 81 (68%) and 5 (4%) partners, respectively. Reasons for patients' complaints included postoperative penile shortening in 60 (30%) cases and poor glandular engorgement in 40 (20%) cases. Partners' main complaint was unnaturalness of the prosthetic erection, a factor reported by 30 (25%) subjects. Complications requiring surgical exploration included infection in 12 patients (6%) and mechanical failure in 8 patients (4%). Kaplan-Meier estimates demonstrated significantly decreased mechanical survival for the Ultrex type of cylinders compared to the CX type of cylinders.
AMS three-piece inflatable implants provide an overall patient and partner satisfaction rate of 92 and 96%, respectively. However, postoperative penile shortening and poor glandular engorgement were the causes of some complaints among the patient population as well as the unnaturalness of prosthetic erection among female partners. In the long-term, mechanically speaking, CX cylinders seem to be more reliable than the Ultrex ones.
Erectile dysfunction (ED), a wide spread and troublesome condition among middle-aged men, is partly vascular in origin. In the Massachusetts Male Aging Study, a random-sample cohort study, we investigated the relationship between baseline risk factors for coronary heart disease and subsequent ED, on the premise that subclinical arterial insufficiency might be manifested as ED.
Men ages 40-70, selected from state census lists, were interviewed in 1987-1989 and reinterviewed in 1995-1997. Data were collected and blood was drawn in participants' homes. ED was assessed from responses to a privately self-administered questionnaire. Analysis was restricted to 513 men with no ED at baseline and no diabetes, heart disease, or related medications at either time.
Cigarette smoking at baseline almost doubled the likelihood of moderate or complete ED at followup (24% vs. 14%, adjusted for age and covariates, P = 0.01). Cigar smoking and passive exposure to cigarette smoke also significantly predicted incident ED, as did overweight (body-mass index > or =28 kg/m(2)) and a composite coronary risk score. Weaker prospective associations were seen for hypertension and dietary intake of cholesterol and unsaturated fat.
Erectile dysfunction and coronary heart disease share some behaviorally modifiable determinants in men who, like our sample, are free of manifest ED or predisposing illness. Open questions include whether modification of coronary risk factors can prevent ED and whether ED may serve as a sentinel event for coronary disease.
The objective of the present study was to investigate the effect of oral treatment of Tribulus terrestris (TT) extract on the isolated corpus cavernosal tissue of New Zealand white (NZW) rabbits and to determine the mechanism by which protodioscin (PTN), a constituent of the TT, exerts its pharmacological effects.
Twenty-four NZW rabbits were randomly assigned to 4 experimental groups of 6 each. Group I served as control. Groups II to IV were treated with the extract at different dose levels, i.e. 2.5 mg/kg, 5 mg/kg and 10 mg/kg body weight, respectively. The TT extract was administered orally, once daily, for a period of 8 weeks. The rabbits were then sacrificed and their penile tissue isolated to evaluate the responses to both contracting and relaxing pharmacological agents and electrical field stimulation (EFS).
PTN on its own had no effect on the isolated corpus cavernosal strips. The relaxant responses to EFS, acetylcholine and nitroglycerin in noradrenaline precontracted tissues from treated groups showed an increase in relaxation of a concentration dependent nature compared to that of the tissues from control group. However, the contractile, anti-erectile response of corpus cavernosal tissue to noradrenaline and histamine showed no significant change between the treatment and the control groups.
The relaxant responses to acetylcholine, nitroglycerin and EFS by more than 10%, 24% and 10% respectively compared to their control values and the lack of such effect on the contractile response to noradrenaline and histamine indicate that PTN has a proerectile activity. The enhanced relaxant effect observed is probably due to increase in the release of nitric oxide from the endothelium and nitrergic nerve endings, which may account for its claims as an aphrodisiac. However, further study is needed to clarify the precise mechanism of its action.
Traditional herbs have been a revolutionary breakthrough in the management of erectile dysfunction and have become known world‐wide as an ‘instant’ treatment. The modern view of the management of erectile dysfunction subscribes to a single etiology, i.e. the mechanism of erection. A large number of pharmacological agents are orally consumed and vasoactive agents inserted intraurethrally or injected intrapenially to regain good erection.
Modern phytochemicals have developed from traditional herbs. Phytochemicals focus their mechanism of healing action to the root cause, i.e. the inability to control the proper function of the whole body system. Hence phytochemicals manage erectile dysfunction in the frame of sexual dysfunction as a whole entity.
Protodioscin is a phytochemical agent derived from Tribulus terrestris L plant, which has been clinically proven to improve sexual desire and enhance erection via the conversion of protodioscine to DHEA (De‐Hydro‐Epi‐Androsterone).
Preliminary observations suggest that Tribulus terrestris L grown on different soils does not consistently produce the active component Protodioscin.
Further photochemical studies of many other herbal plants are needed to explain the inconsistent results found with other herbal plants, such as in diversities of Ginseng, Eurycoma longifolia, Pimpinella pruacen, Muara puama, Ginkgo biloba, Yohimbe etc.
To our knowledge a causal relationship between altered levels of androgens and erectile dysfunction has not yet been established. We reviewed the literature to assess the usefulness of androgen replacement for erectile dysfunction.
Meta-analysis was chosen as the method of evaluating the literature. Study inclusion criteria were testosterone given as the only therapy for erectile dysfunction and a clearly stated definition of response for evaluating treatment success or failure.
We evaluated 73 articles obtained by a MEDLINE search of 1966 to 1998 and included 16 in our study. The overall response rate was 57%. In the 9 series with response rate by etiology patients with primary versus secondary testicular failure had a response rate of 64% versus 44% (p <0.001). Intramuscular and oral methods of delivery were equivalent with a response rate of 51.3% and 53.2%, respectively. However, the response to transdermal therapy was significantly different from that of intramuscular and oral treatment (80.9% versus 51.3% and 53.2%, respectively, p <0.001). The mean confidence level response for testosterone treatment was 16. 7% in the placebo and 65.4% in the treated group (p <0.0001).
Our meta-analysis of the usefulness of androgen replacement therapy for erectile dysfunction indicates that the response rate for a primary etiology was improved over that for a secondary etiology, transdermal testosterone therapy was more effective than intramuscular or oral treatment, and intramuscular and oral treatments were equivalent. In addition, there was a statistically significant difference in favor of testosterone over placebo, implying a role for supplementation in select groups.
This paper: (i) describes the worldwide prevalence of erectile dysfunction (ED); (ii) presents age-specific incidence rates for ED in the US; (iii) summarizes some key epidemiologic correlates of ED in the general population; and (iv) considers the possibility that ED may be a biobehavioral marker (sentinel event) of subsequent cardiovascular disease in men. Clinical, anthropometric, life style and hormonal data are presented from the milestone Massachusetts Male Aging Study (MMAS), a large (over 1000) prospective cohort of randomly sampled community-dwelling, normally aging men. Newly updated population prevalence and (more importantly) age-specific incidence rates are reported. We also estimate the likely magnitude of ED that will accompany the worldwide globalization of aging. Key correlates (predictors) of incident ED, especially vasculogenic influences, are identified and discussed. In conclusion, ED is a common biobehavioral phenomenon and there are strong physiological and epidemiological reasons for considering it a major marker (or predictor) of subsequent cardiovascular disease in men. International Journal of Impotence Research (2000) 12, Suppl 4, S6-S11.
To asses the efficacy and safety of Topiglan (1% alprostadil in a formulation with 5% SEPA [soft enhancer of percutaneous absorption]) or placebo gel (0.25 mL) applied to the glans penis only in 60 patients with moderate to severe erectile dysfunction in a two-visit, in-office clinical trial.
During the first visit, open-label placebo gel was applied. At the second visit, blind, random allocation to Topiglan (n = 31) or placebo gel (n = 29) occurred. Thirty minutes after application, an erotic movie showing heterosexual sex began; at 45 minutes, a penile vibrator was used. Audiovisual and tactile stimulation were discontinued at 65 minutes, and the patient was observed until 90 minutes after application. At the scheduled time points, the erection response was assessed by both the investigator and the patient and signs and symptoms of tolerance were evaluated.
Topiglan produced a greater angle of erection (P = 0.003) and maximum rigidity (P = 0.033) compared with the placebo gel. The responses to Topiglan were greater than to placebo gel at all time points after application, with the greatest differences observed at 45 and 60 minutes. Of the 31 patients treated with Topiglan, 12 (38.9%) achieved an erection judged sufficient for vaginal penetration (P = 0.005); 2 (6.9%) of the 29 patients who received placebo gel did so. Penile erythema was more common with Topiglan; symptoms of minor to mild warmth or burning and, less commonly, tingling and coolness were reported by most patients after both Topiglan and placebo gel application. No significant changes in vital signs were noted.
Topiglan applied to the glans penis increased penile rigidity and expectations regarding vaginal penetration in patients with erectile dysfunction.
Smoking is associated with an increased risk of developing erectile dysfunction (ED). For example, in the Massachusetts Male Aging Study (MMAS), cigarette smoking amplified the risk of ED associated with other risk factors (e.g. hypertension, diabetes and dyslipidaemia) or with ageing. At the molecular level, several changes associated with smoking have been documented in man and experimental models. These changes could contribute to the pathogenesis of ED. Furthermore, studies performed in dogs demonstrated a smoking-related reduction in arterial flow and venous restriction. Similarly, impaired penile flow has been documented in men who smoke. Cigarette smoking also interferes with the effectiveness of intracavernous papaverine and PGEI. Quitting is the 'first-line' therapy of ED and one of the most important measures for the prevention of atherosclerosis.
The development of external erection devices has evolved as the social stigma surrounding the treatment of erectile dysfunction has gradually disappeared during the late twentieth century. Although the success of surgical and medical therapy for erectile dysfunction has been documented, especially since the introduction of sildenafil citrate, patient demand for an effective, noninvasive, drug-free management of erectile dysfunction has remained. As the population continues to age, acquiring the comorbidities commonly associated with erectile dysfunction, such as hypertension, diabetes mellitus, and atherosclerotic vascular disease, the demand for such treatment should persist. This article examines the development, mechanism of action, efficacy, and patient satisfaction with regard to vacuum constriction and external erection devices.
To establish the efficacy and safety of a fixed, 3-mg dose of apomorphine SL compared with placebo, and to compare 3 mg with 4 mg apomorphine SL in patients with erectile dysfunction.
This randomized, double-blind, crossover study included 296 heterosexual men with ED of various etiologies and severities. Two crossover groups were evaluated separately: 3 mg apomorphine SL vs. placebo (n = 194), and 3 vs. 4 mg apomorphine SL (n = 102). The primary efficacy variable was the percentage of attempts resulting in erections firm enough for intercourse; additional variables included the percentage of attempts resulting in intercourse and time to erection. Partner assessments were also analyzed.
3 mg apomorphine SL was significantly more effective than placebo (p<0.001) for the percentage of attempts resulting in erections firm enough for intercourse and resulting in intercourse, as assessed by both patients and partners. Median time to erection was 18.8 min. The 3-mg dose was not significantly different from 4 mg in the evaluation of efficacy variables, but the incidence of adverse events was higher with 4 mg. Nausea was the most common event, reported by 3.3% of patients on 3 mg vs. 14.1% on 4 mg; in the placebo comparison, nausea was reported by 7.0% of patients taking 3 mg apomorphine SL vs. 1.1% of those taking placebo.
3 mg apomorphine SL was significantly more effective than placebo and comparable to 4 mg, while offering an improved risk-benefit ratio.
Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardenafil x HCl (hereafter called vardenafil) and sildenafil were given intravenously, and measurements were taken for 0-5 h. The effects of phentolamine and milrinone were also evaluated. Vardenafil (0.1-3 mg/kg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect. Sildenafil was effective in this model after i.v. administration. The alpha-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower t(max) compared with vardenafil and sildenafil. Intravenous administration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of erectile dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis.
Erectile dysfunction (ED) affects as many as 30 million men in the United States. Its risk factors are similar to those for atherosclerotic heart disease. Physicians should ask male patients--particularly those with cardiovascular disease--about ED and men with confirmed ED about cardiovascular risk factors. Oral sildenafil is an effective therapy for both organic and psychogenic ED; it is contraindicated in patients taking organic nitrates.
Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, but also by visual, olfactory, and imaginary stimuli. The reflex involves both autonomic and somatic efferents and is modulated by supraspinal influences. Several central transmitters involved in the erectile control have been identified. Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as oxytocin and adrenocorticotropic/alpha-melanocyte-stimulating hormone, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via stimulation of alpha(1)-adrenoceptors. Neurogenic NO is considered the most important factor for relaxation of penile vessels and corpus cavernosum. The role of other mediators released from nerves or endothelium has not been definitely established. Erectile dysfunction (ED) may be due to inability of penile smooth muscles to relax. This inability can have multiple causes. However, patients with ED respond well to the pharmacological treatments that are currently available. The drugs used are able to substitute, partially or completely, the malfunctioning endogenous mechanisms that control penile erection. Most drugs have a direct action on penile tissue facilitating penile smooth muscle relaxation, including prostaglandin E(1), NO donors, phosphodiesterase inhibitors, and alpha-adrenoceptor antagonists. Dopamine receptors in central nervous centers participating in the initiation of erection have been targeted for the treatment of ED. Apomorphine, administered sublingually, is the first of such drugs.
The tubers of Lepidium meyenii contain the benzylated derivative of 1,2-dihydro-N-hydroxypyridine, named macaridine, together with the benzylated alkamides (macamides), N-benzyl-5-oxo-6E,8E-octadecadienamide and N-benzylhexadecanamide, as well as the acyclic keto acid, 5-oxo-6E,8E-octadecadienoic acid. The structure elucidation of the isolated compounds was based primarily on 1D and 2D NMR spectroscopic analyses, including 1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC and 1H-1H NOESY experiments, as well as from 1H-15N NMR HMBC correlations for macaridine and N-benzylhexadecanamide.
Background Sildenafil is a potent inhibitor of cyclic guanosine monophosphate in the corpus cavernosum and therefore increases the penile response to sexual stimulation. We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, or mixed causes.
We conducted integrated analyses of the efficacy and safety of tadalafil, a potent, selective phosphodiesterase 5 inhibitor, for the treatment of erectile dysfunction.
A total of 1,112 men with a mean age of 59 years (range 22 to 82) and mild to severe erectile dysfunction of various etiologies were randomized to placebo or tadalafil, taken as needed without food or alcohol restrictions, at fixed daily doses of 2.5 mg, 5 mg, 10 mg, or 20 mg up to a maximum of once daily [DOSAGE ERROR CORRECTED] in 5 randomized, double-blind, placebo controlled trials lasting 12 weeks. The 3 co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function and the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile. Additional efficacy instruments included a Global Assessment Question.
Compared with placebo, tadalafil significantly enhanced all efficacy outcomes. Patients receiving 20 mg. tadalafil experienced a significant mean improvement of 7.9 in International Index of Erectile Function erectile function domain score from baseline (p <0.001 versus placebo), 75% of intercourse attempts (Sexual Encounter Profile question 3, a secondary efficacy outcome) were successfully completed (p <0.001 versus placebo) and 81% reported improved erections at end point compared with 35% in the control group (p <0.001). Tadalafil was consistently efficacious across disease severities and etiologies, as well as in patients of all ages. Tadalafil was well tolerated, and headache and dyspepsia were the most frequent adverse events.
Tadalafil was effective and well tolerated in this patient population.
Traditional implantation of the AMS Sphincter 800 Urinary Control System (American Medical Systems, Minnetonka, Minnesota) requires 2 incisions. The cuff is placed via a perineal incision, and the pressure regulating balloon and pump are placed through a separate suprapubic incision. We describe a novel implantation of all the artificial urinary sphincter components using a single upper scrotal incision. The scrotal incision allows excellent access to the proximal bulbar urethra and retropubic and subdartos spaces, and leaves the bulbocavernosus muscle intact.
A total of 37 patients have undergone artificial urinary sphincter implantation using the new operative technique for revisions or reimplantations of a sphincter previously removed for infection/erosion (12) or as an initial procedure (25). In 9 of the 25 patients and 2 of the 12 dual implantation of a 3-piece penile prosthesis through the same incision was performed.
All patients are using the devices. Of the patients 66% are completely dry with no pad use and the remainder use 1 pad for accident prevention. Operative time was reduced due to easier exposure of the urethra and a second incision for placement of the pressure regulating balloon was not necessary. Followup at 1 year shows no difference in complication rate with the single incision technique compared to the traditional method.
Artificial urinary sphincter implantation through a single scrotal incision is easier and faster than the traditional 2-incision technique. Success in achieving continence is similar to traditional methods. Long-term followup is necessary to ensure that complications remain low.
The durability of key efficacy response parameters and safety of vardenafil was evaluated in a pivotal trial conducted in a broad population of men with erectile dysfunction (ED) in North America. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel-group, 6-month comparison study, men >18 years of age with ED for >6 months received 5-mg, 10-mg, and 20-mg doses of vardenafil as needed for up to 26 weeks. The primary efficacy variables were the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain scores, and the Sexual Encounter Profile (SEP) mean per-patient success rates for penetration (SEP question 2) and maintenance of erections (SEP question 3). Safety data were also collected over time. Improvement in all primary efficacy variables was observed in all vardenafil groups versus placebo. These improvements occurred early and were either sustained or increased through week 26. Vardenafil in 10-mg and 20-mg doses was significantly superior to placebo at all time points for all efficacy variables (P <0.01), and all doses were superior to placebo at endpoint (P <0.001). Most treatment-emergent adverse events (headache, flushing, dyspepsia, and rhinitis) were mild or moderate in intensity, and incidence generally decreased over time. All 3 doses of vardenafil were superior to placebo across all primary efficacy variables and all study time points in a broad range of patients with ED, regardless of etiology or severity. Vardenafil was well tolerated. These results demonstrate that vardenafil provides sustained efficacy with reduced incidence of nuisance side effects over time. High resolution video, medium resolution video, low resolution video.
This open-label study investigated the efficacy of sildenafil citrate at 12 hours postdose among prior treatment responders.
Eight 100-mg doses of sildenafil were provided to 40 eligible patients with erectile dysfunction (ED), who were to record the results of each sexual attempt in a patient diary. Each patient was instructed to make a sexual attempt at 1 and 12 hours postdose on 4 occasions (part 1) and only at 12 hours postdose on 4 subsequent occasions (part 2).
Of 40 enrolled patients, 34 (85%) completed the study. In these evaluable patients, 97% and 74% of patients achieved erections that resulted in successful intercourse at 1 hour and 12 hours postdose, respectively. There was a nonsignificant reduction in the percentage of responders at 12 hours during part 1 versus part 2 of this study (71% versus 78%).
This study demonstrates that, in the majority of these patients with ED, sildenafil remains clinically active 12 hours after administration. Larger studies may be necessary to confirm and clarify the therapeutic window of sildenafil.
To assess prevalence and risk factors for erectile dysfunction (ED) by using the International Index of Erectile Function- 5 (IIEF-5) in men undergoing a health investigation.
Men aged 20-80 years participating in a health-screening project in the area of Vienna completed the IIEF-5 for evaluation of ED. In parallel, all men underwent a detailed health examination including physical assessment, evaluation of various life-style factors, medical history and a blood analysis.
A total of 2869 men were analysed. According to the IIEF-5 score, 32.2% reported on any degree of ED (IIEF-5 score <22), 23.7% had mild ED (IIEF-5 score 17-21), 5.0% mild to moderate ED (IIEF-5 score 12-16), 2.2% moderate ED (IIEF-5 score 8-11) and 1.3% severe ED (IIEF-5 score 5-7). The proportion of men with ED remained stable from 20 to 50 years (26-29%) and increased thereafter to 37.5% (51-60 years) and to 71.2% in those 71-80 years of age. Severe ED (IIEF-5 score 5-7) increased from 0.4% (20-30 years) to 0.5% (41-50 years), 1.3% (51-60 years) and to 9.6% in those aged 71-80 years. Risk factors for ED were age, diabetes (OR: 3.0; 95%CI: 1.53-5.87), hyperlipidemia (OR: 2.29; 95%CI: 1.42-3.7), lower urinary tract symptoms (OR: 2.2; 95%CI: 1.76-2.76), hypertension (OR: 2.05; 95%CI: 1.61-2.6), psychological stress (OR: 1.68; 95%CI: 1.43-1.98) and low physical activity (OR: 1.35; 95%CI: 1.15-1.6) (all, p < 0.05).
Overall, 32.2% of men in our study had ED according to the IIEF-5. Apart from age, most important risk factors for ED were diabetes, hyperlipidemia, lower urinary tract symptoms, hypertension and psychological stress.
Erectile dysfunction (ED) is a highly prevalent disorder associated with a significant burden of illness. The prevalence and incidence of ED are strongly age-related, affecting more than half of men >60 years. The first Princeton Consensus Conference (Princeton I) in 1999 developed guidelines for safe management of cardiac patients regarding sexual activity and the treatment of ED.
The second conference (Princeton II) was convened to update the recommendations based on the expanding knowledge base and new treatments available. This article reviews and expands on the Princeton II guidelines to address sexual dysfunction and cardiac risk.
A consensus panel of experts reviewed recent multinational studies in safety and drug interaction data for three phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease.
Erectile dysfunction is an early symptom or harbinger of cardiovascular disease, due to the common risk factors and pathophysiology mediated through endothelial dysfunction. Major comorbidities include diabetes, hypertension, hyperlipidemia and heart disease. Any asymptomatic man who presents with ED that does not have an obvious cause (e.g., trauma) should be screened for vascular disease and have blood glucose, lipids, and blood pressure measurements. Ideally, all patients at risk but asymptomatic for coronary disease should undergo an elective exercise electrocardiogram to facilitate risk stratification. Lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease, is literature-supported.
The recognition of ED as a warning sign of silent vascular disease has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise. Men with ED and other cardiovascular risk factors (e.g., obesity, sedentary lifestyle) should be counseled in lifestyle modification.
Penile prostheses, introduced as the first effective organic treatment for erectile dysfunction over three decades ago, have an important role in the treatment of erectile dysfunction when other nonprosthetic treatment options have proven unsatisfactory. Although they are the least chosen and most invasive treatment option, they have the highest satisfaction rate of all available ED options and provide a predictable and reliable result.
To provide recommendations/guidelines concerning state-of-the-art knowledge for utilization of the penile prosthesis in the management of men with erectile dysfunction.
An International Consultation in collaboration with the major sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. There were 10 experts from seven countries concerning the Penile Implant for Erectile Dysfunction.
Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.
Recommendations/guidelines for penile prosthesis (hydraulic, semi-rigid and soft silicone) insertion for management of men with erectile dysfunction were updated. Consensed issues included: criteria for patient selection, informed consent procedures, strategies for preoperative preparation, operative incisions/technical considerations and outcome results in terms of patient satisfaction and device survival. Updated information was reviewed concerning therapies for device failures, device insertion in scarred corporal bodies and strategies for managing implant infections.
There is a need for more research in developing management strategies for insertion of penile prostheses in men with ED.
Erectile dysfunction (ED) is defined as the consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity (2nd International Consultation on Sexual Dysfunction-Paris, June 28th-July 1st, 2003). Following the discovery and introduction of sildenafil, research on the mechanisms underlying penile erection has had an enormous boost and many preclinical and clinical papers have been published in the last 5 years. This review is structured in order to give the reader an overview of the clinical and preclinical data available on the peripheral regulation of and the mediators involved in human penile erection. The most widely accepted risk factors for ED are discussed. The article is focused on human data, and the safety and effectiveness of the 3 commercially available Phosphodiesterase-5 (PDE5) inhibitors used to treat ED are also discussed.