Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation

EURURO-3367; No. of Pages 11 Guidelines – Sexual Medicine Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation Konstantinos Hatzimouratidis Edouard Amar , Ian Eardley Francois Giuliano Dimitrios Hatzichristou Francesco Montorsi Yoram Vardi Eric Wespes a 2nd Department of Urology, Aristotle University of Thessaloniki, Thessaloniki, Greeceb Hoˆpital Bichat, Paris, Francec Pyrah Department of Urology, St. James University Hospital, Leeds, UKd AP-HP, Neuro-Urology-Andrology, Raymond Poincare´ Hospital, Garches, Francee Department of Urology, University Vita-Salute San Raffaele, Scientific Institute H. San Raffaele, Milan, Italyf Department of Neuro-Urology, Rambam Medical Centre and Technion Faculty of Medicine, Haifa, Israelg Hoˆpital Civil de Charleroi, Hoˆpital Erasme, Urology Department, Brussels, Belgium Context: Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male Accepted February 10, 2010 Published online ahead of Objective: To present the updated version of 2009 European Association of Urology (EAU) guidelines print on February 20, 2010 on ED and PE.
Evidence acquisition: A systematic review of the recent literature on the epidemiology, diagnosis,and treatment of ED and PE was performed. Levels of evidence and grades of recommendation were Erectile dysfunction Evidence synthesis: ED is highly prevalent, and 5–20% of men have moderate to severe ED. ED shares Male sexual dysfunction common risk factors with cardiovascular disease. Diagnosis is based on medical and sexual history, Premature ejaculation including validated questionnaires. Physical examination and laboratory testing must be tailored to the patient's complaints and risk factors. Treatment is based on phosphodiesterase type 5 inhibitors(PDE5-Is), including sildenafil, tadalafil, and vardenafil. PDE5-Is have high efficacy and safety rates, even in difficult-to-treat populations such as patients with diabetes mellitus. Treatment options forpatients who do not respond to PDE5-Is or for whom PDE5-Is are contraindicated include intracav- ernous injections, intraurethral alprostadil, vacuum constriction devices, or implantation of a penileprosthesis.
PE has prevalence rates of 20–30%. PE may be classified as lifelong (primary) or acquired (secondary). Diagnosis is based on medical and sexual history assessing intravaginal ejaculatory latency time, perceived control, distress, and interpersonal difficulty related to the ejaculatory dysfunction. Physical examination and laboratory testing may be needed in selected patients only.
Pharmacotherapy is the basis of treatment in lifelong PE, including daily dosing of selective serotonin reuptake inhibitors and topical anaesthetics. Dapoxetine is the only drug approved for theon-demand treatment of PE in Europe. Behavioural techniques may be efficacious as a monotherapy or in combination with pharmacotherapy. Recurrence is likely to occur after treatment withdrawal.
Conclusions: These EAU guidelines summarise the present information on ED and PE. The extended version of the guidelines is available at the EAU Web site # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. 2nd Department of Urology, Aristotle University of Thessaloniki, 54006,Thessaloniki, Greece. Tel. +302310991543; Fax: +302310676092.
E-mail address: (K. Hatzimouratidis).
0302-2838/$ – see back matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi: EURURO-3367; No. of Pages 11 Table 1 – Indications for specific diagnostic tests Patients with primary erectile disorder (not caused by organic disease or Erectile dysfunction (ED; or impotence) and premature psychogenic disorder)Young patients with a history of pelvic or perineal trauma who could ejaculation (PE) are the two most prevalent complaints in benefit from potentially curative vascular surgery male sexual medicine. The most recent summary of the Patients with penile deformities (eg, Peyronie's disease, congenital European Association of Urology (EAU) guidelines on ED curvature) that might require surgical correction was published in 2006. The EAU's Guidelines Office decided Patients with complex psychiatric or psychosexual disordersPatients with complex endocrine disorders to expand these guidelines to include PE. Therefore, the new Specific tests may also be indicated at the request of the patient or his guidelines include an update of the ED guidelines and a completely new section on PE based on a review of available For medicolegal reasons (eg, penile prosthesis implant, sexual abuse) scientific information, current research, and clinical prac-tice in the field. (The extended version of the guidelines isavailable at the EAU Web site dysfunction or congestive heart failure (New York Heart ].) Levels of evi- Association class I), postsuccessful coronary revascularisa- dence and grades of recommendation also were assigned.
tion, controlled hypertension, and mild valvular disease. All The aim of this review is to present a summary of the 2009 other patients were included in intermediate- or high-risk update of the EAU guidelines on ED and PE.
categories and required a cardiology consultation prior toengaging in sexual activity (sexual activity for high-risk Erectile dysfunction patients is not recommended).
Definition, epidemiology, and risk factors Specific examinations and tests Although most patients with ED can be managed within the ED is the persistent inability to attain and maintain an primary care setting, some circumstances, presented in erection sufficient to permit satisfactory sexual perfor- require specific diagnostic testing Specific mance . ED affects physical and psychosocial health and diagnostic tests are presented in . Nocturnal penile has a significant impact on the quality of life (QoL) of tumescence and rigidity testing using Rigiscan should take sufferers and their partners and families. Epidemiologic place for at least two nights. A functional erectile studies of ED suggest that approximately 5–20% of men mechanism is indicated by an erectile event of 60% have moderate to severe ED . The difference in reported rigidity recorded on the tip of the penis lasting for 10 min incidences is probably due to differences in the methodol- The intracavernous injection test provides limited ogy and in the age and socioeconomic status of the study information about vascular status; however, duplex ultra- sound provides a simple (albeit intrusive) way of assessing ED shares common risk factors with cardiovascular vascular status. Further vascular investigation is unneces- disease, including lack of exercise, obesity, smoking, sary if duplex ultrasound is normal, as indicated by a peak hypercholesterolaemia, and metabolic syndrome . The systolic blood flow >30 cm/s and a resistance index >0.8. If risk of ED may be reduced by modifying these risk factors, the ultrasound is abnormal, however, arteriography and particularly exercising or losing weight . Another risk dynamic infusion cavernosometry and cavernosography factor for ED is radical prostatectomy (RP) in any form should be performed only in patients who are potential (open, laparoscopic, or robotic) because of the risk of candidates for vascular reconstructive surgery .
cavernosal nerve injury, poor oxygenation of the corpora A summary of recommendations for the diagnostic cavernosa, and vascular insufficiency. Some 25–75% of men work-up of ED is presented in .
undergoing RP experience postoperative ED. Patients beingconsidered for nerve-sparing RP, ideally, should be potent, Treatment of erectile dysfunction and the cavernosal nerves must be preserved to ensureerectile function recovery after RP .
Only certain types of ED have the potential to be cured withspecific treatments. For psychogenic ED, psychosexual Diagnosis and work-up therapy may be given either alone or with another The basic work-up (minimal diagnostic evaluation) out- Table 2 – Specific diagnostic tests lined in must be performed in every patient with ED Nocturnal penile tumescence and rigidity using Rigiscan . Because of the potential cardiac risks associated with sexual activity, the Second Princeton Consensus Conference  Intracavernous vasoactive drug injection Duplex ultrasound of the cavernous arteries stratified patients with ED wanting to initiate or resume  Dynamic infusion cavernosometry and cavernosography sexual activity into three risk categories. The low-risk group  Internal pudendal arteriography included asymptomatic patients with fewer than three risk Neurologic studies (eg, bulbocavernosus reflex latency, nerve-conduction factors for coronary artery disease (excluding male gender), mild or stable angina (evaluated and/or being treated), Specialised psychodiagnostic evaluation uncomplicated past myocardial infarction, left ventricular Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi:

EURURO-3367; No. of Pages 11 Fig. 1 – Basic diagnostic work-up in patients with erectile dysfunction.
ED = erectile dysfunction; IIEF = International Index of Erectile Function.
therapeutic approach, but this therapy takes time and has endocrinologic causes for testicular failure have been had variable results .
excluded. Although some data suggest that testosterone For posttraumatic arteriogenic ED in young patients, administration does not cause prostate cancer, it is currently surgical penile revascularisation has a 60–70% long-term contraindicated in men with a history of prostate carcinoma or with symptoms of prostatism. Close follow-up is neces- For hormonal causes of ED, testosterone replacement sary, including digital rectal examination, serum prostate- therapy is effective but should be used only after other specific antigen testing, and haematocrit assessment as Table 3 – Recommendations for the diagnostic work-up of erectile dysfunction (ED) Clinical use of a validated questionnaire related to ED may help assess all sexual function domains and the effect of a specific treatment modality.
Physical examination is needed in the initial assessment of ED to identify underlying medical conditions associated with ED.
Routine laboratory tests, including glucose-lipid profile and total testosterone, are required to identify and treat any reversible risk factors and modifiable lifestyle factors.
Specific diagnostic tests are indicated by only a few conditions.
LE = level of evidence; GR = grade of recommendation.
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EURURO-3367; No. of Pages 11 well as monitoring of the development of hepatic or prostatic Most men with ED will be treated with options that are not cause specific . This approach requires a structured Although there is some debate, the use of pro-erectile treatment strategy that depends on efficacy, safety, drugs following RP seems important in achieving erectile invasiveness, and cost as well as patient and partner function following surgery. Several trials have shown higher satisfaction. The choice of treatment options must consider rates of recovery of post-RP erectile function in patients the effects on patient and partner satisfaction and other QoL receiving any phosphodiesterase type 5 inhibitor (PDE5-I) factors as well as efficacy and safety. A treatment algorithm or intracavernosal injections (therapeutic or prophylactic).
for ED is given in Rehabilitation should start as soon as possible following A summary of recommendations for the treatment of ED Fig. 2 – Treatment algorithm for erectile dysfunction (ED).
PDE5 = phosphodiesterase type 5.
Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi: EURURO-3367; No. of Pages 11 Table 4 – Recommendations for the treatment of erectile dysfunction (ED) Lifestyle changes and risk factor modification must precede or accompany ED treatment.
Pro-erectile treatments must be given at the earliest opportunity after radical prostatectomy.
If a curable cause of ED is found, treat the cause first.
PDE5-Is are first-line therapy.
Daily administration of PDE5-Is may improve results and restore erectile function.
Inadequate/incorrect prescription and poor patient education are the main causes of a lack of response to PDE5-Is.
Testosterone replacement restores efficacy in hypogonadic nonresponders to PDE5-Is.
Apomorphine can be used in mild to moderate ED, psychogenic ED, or in patients with contraindications to PDE5-Is.
A vacuum constriction device can be used in patients with stable relationship.
Intracavernous injection is second-line therapy.
Penile implant is third-line therapy.
LE = level of evidence; GR = grade of recommendation; PDE5-I = phosphodiesterase type 5 inhibitor.
First-line therapy Efficacy was confirmed in postmarketing studies. Vardenafil Oral pharmacotherapy. Three potent selective PDE5-Is also improved erections in difficult-to-treat subgroups.
have been approved by the European Medicines Agency forthe treatment of ED . They are not initiators of erection Choice of or preference for different phosphodiesterase and require sexual stimulation for an erection to occur.
type 5 inhibitors. The choice of a PDE5-I depends on the Efficacy is defined as rigidity sufficient for vaginal frequency of intercourse (occasional use or regular therapy, three to four times weekly) and the patient's personal Sildenafil (Viagra), launched in 1998, was the first PDE5-I experience with the agent. Consideration should be given to available. It is effective 30–60 min from administration. A which drug better fits the patient's premorbid sexual script heavy fatty meal may reduce or prolong absorption. It is with his partner to optimise response. Patients need to administered in 25-, 50-, and 100-mg doses. The recom- know whether a drug is short or long acting, its possible mended starting dose is 50 mg, which is adapted according disadvantages, and how to use it.
to patient response and side-effects. Efficacy may last for upto 12 h. In premarketing studies, after 24 wk of treatment in On-demand or chronic use of phosphodiesterase type 5 a dose-response study, improved erections were reported inhibitors. Although PDE5-Is were initially introduced as on- by 56%, 77%, and 84% of men taking 25, 50, and 100 mg of demand treatment, in 2008, tadalafil was also approved for sildenafil, respectively, compared with 25% of men taking continuous, everyday use in 2.5- and 5-mg doses. Two placebo. The efficacy of sildenafil in almost every subgroup studies assessing daily use of 5- and 10-mg tadalafil of patients with ED has been well established in pre- and for 12 wk and daily use of 2.5- and 5-mg tadalafil for 24 wk showed that daily dosing was well tolerated and signifi- Tadalafil (Cialis) was licensed for ED in 2003. It is cantly improved erectile function. Similar results have been effective from 30 min after administration, but its peak found in diabetic patients . These studies, however, efficacy occurs after about 2 h. Efficacy is maintained for up lacked an on-demand treatment arm. Daily tadalafil to 36 h. Its efficacy is not affected by food. It is administered provides an alternative to on-demand dosing for couples in 10- and 20-mg doses. The recommended starting dose is who prefer spontaneous rather than scheduled sexual 10 mg, which is adapted according to patient response and activity or who have frequent sexual activity. Daily dosing side-effects. In premarketing dose-response studies, im- overcomes the requirement for dosing and sexual activity to proved erections were reported after 12 wk of treatment by be temporally linked. Other studies have shown that 67% and 81% of men taking 10 mg and 20 mg of tadalafil, chronic but not on-demand tadalafil treatment improved respectively, compared with 35% of men taking placebo. The endothelial function, with sustained effects after its results were confirmed in postmarketing studies. Tadalafil discontinuation. This finding was confirmed in another also improved erections in difficult-to-treat subgroups.
study of chronic sildenafil use in men with type 2 diabetes Vardenafil (Levitra) was licensed for ED in 2003. It is . In contrast, a randomised clinical study found that effective 30 min from administration. A fatty meal (>57% in once-daily dosing of vardenafil at 10 mg/d did not offer any fat) reduces its effect. It is administered in 5-, 10-, and sustainable effect after cessation of treatment compared 20-mg doses. The recommended starting dose is 10 mg, with on-demand vardenafil in patients with mild to which is adapted according to the response and side-effects.
In vitro, it is 10-fold more potent than sildenafil; however,this does not necessarily mean greater clinical efficacy. In Adverse events. Common adverse events include premarketing dose-response studies, improved erections headache (10–16%), flushing (5–12%), dyspepsia (4–12%), after 12 wk of treatment were reported by 66%, 76%, and nasal congestion (1–10%), and dizziness (2–3%) 80% of men taking 5 mg, 10 mg, and 20 mg of vardenafil, Sildenafil and vardenafil have been associated with visual respectively, compared with 30% of men taking placebo.
abnormalities in <2% of patients, while tadalafil has been Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi: EURURO-3367; No. of Pages 11 associated with back pain/myalgia in 6% of patients.
associated hypogonadism, changing to another PDE5-I, or Adverse events are generally mild in nature and self- continuous use of a PDE5-I. Limited evidence supports using limited by continuous use, and the dropout rate due to these interventions Additionally, an accumulating adverse events is similar to that seen with placebo.
body of evidence supports the use of psychosexualeducational counselling in combination with pharmaceuti- Cardiovascular safety. Clinical trials and postmar- cal treatments to further optimise response.
keting data of all PDE5-Is have demonstrated no increase inmyocardial infarction rates No PDE5-I has adversely Vacuum constriction devices. A vacuum constriction affected total exercise time or time to ischemia during device (VCD) applies negative pressure to the penis to exercise testing in men with stable angina. In fact, they may draw venous blood into the penis, which is then retained by improve exercise tests.
application of a visible constricting band at the base of the Nitrates are totally contraindicated with all PDE5-Is due penis. This method seems more acceptable to older patients to unpredictable hypotension. The duration of interaction . Efficacy, defined by an erection satisfactory for between organic nitrates and PDE5-Is varies according to intercourse, is as high as 90%. Satisfaction rates range the PDE5-I and nitrate. If a patient develops angina while between 27% and 94% . After 2 yr, only 50–64% of men using a PDE5-I, other antiangina agents may be used instead continue to use VCDs. Most men who discontinue use of of nitroglycerine or until the appropriate time has passed VCDs do so within 3 mo. The adverse effects associated with (24 h for sildenafil or vardenafil and 48 h for tadalafil) .
vacuum therapy are penile pain, numbness, and delayed In general, the adverse event profile of the PDE5-I is not ejaculation; these effects occur in <30% of patients.
worsened, even when the patient is on multiple antihyper-tensive agents.
Second-line therapy Patients not responding to oral drugs may be offered a-Blocker interactions. The concomitant use of intracavernous injections. Alprostadil (Caverject, Edex/ PDE5-Is with a-blockers may result in orthostatic hypoten- Viridal) is the only drug approved for intracavernous sion under some conditions. The labelling for sildenafil treatment of ED. It is the most efficacious monotherapy currently includes a precaution advising that 50 or 100 mg for intracavernous treatment using 5- to 40-mg doses (not 25 mg) of sildenafil should not be taken within 4 h of Erection appears after 5–15 min and lasts according to the taking an a-blocker. The use of vardenafil with an a-blocker is dose injected. The patient should be enrolled in an office- not recommended; however, coadministration of vardenafil based training programme (one or two visits) to learn the with tamsulosin is not associated with clinically significant correct injection process. Efficacy rates are about 70%, with hypotension. Tadalafil is contraindicated in patients taking reported sexual activity after 94% of injections and a-blockers, except for tamsulosin . Generally, the patient satisfaction rates of 87–93.5% in patients and 86–90.3% in should be stable in his a-blocker therapy before using a partners. Dropout rates of 41–68% have been reported, with PDE5-I. The long-acting a-blockers (doxazosin, terazosin) most dropouts occurring within the first 2–3 mo .
should be avoided in this concomitant use. Alfuzosin and Complications of intracavernous alprostadil include tamsulosin are the preferred a-blockers.
penile pain (50% of patients after 11% of injections),prolonged erections (5%), priapism (1%), and fibrosis (2%) Dosage adjustments. Lower doses of PDE5-Is may . Drug combinations (mainly the three-drug combina- be required in patients taking ketoconazole, itraconazole, tion of alprostadil plus papaverine plus phentolamine) may erythromycin, clarithromycin, and HIV protease inhibitors increase efficacy by up to 90%. Fibrosis was found to be (ritonavir, saquinavir) Higher doses of PDE5-Is may be more common (5–10%) if papaverine was used (depending necessary in patients taking rifampicin, phenobarbital, on total dose). After 4 h of erection, patients are advised to phenytoin, or carbamazepine. Kidney or hepatic dysfunction consult their doctors to avoid any damage to the may require dose adjustments. In patients with hypogonad- intracavernous tissue, as this will result in permanent ism, androgen supplementation improves erectile response.
impotence A 19-gauge needle is used to aspirate bloodand decrease the intracavernous pressure. This simple Management of nonresponders to phosphodiesterase technique is usually sufficient to make the penis flaccid. If type 5 inhibitors. The two main reasons that patients fail to the penis then becomes rigid again, phenylephrine should respond to a PDE5-I are either incorrect drug use or be injected into the intracavernous muscle, starting at inefficacy of the drug Physicians should check that the 200 mg every 5 min and increasing to 500 mg if necessary. If patient is using a licensed medication and that the this problem occurs, the dosage of the next intracavernosal medication has been properly prescribed and correctly injection is usually reduced.
used (ie, that there is adequate sexual stimulation and Prostaglandin E1 may be administered intraurethrally dosage and enough time between taking the medication as a semisolid pellet (125–1000 mg) A band placed and an attempt at intercourse).
at the base of the penis improves the resulting rigidity.
The clinical success rate is lower than with intracaver- Provided that a patient is using a PDE5-I appropriately, nosal injections, but about 70% of patients are satisfied or efficacy can be improved in several ways, including very satisfied with treatment. Side-effects include local modification of associated risk factors, treatment of Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi: EURURO-3367; No. of Pages 11 pain (29–41%), dizziness (1.9–14%), and urethral bleeding latency time (IELT) <1–2 min, is about 2–5% The aetiology of PE is unknown, with little data to supportsuggested biological and psychological hypotheses, includ- Third-line therapy (penile prostheses) ing anxiety, penile hypersensitivity, and serotonin receptor Surgical implantation of a penile prosthesis may be dysfunction In contrast to ED, the prevalence of PE is considered in patients who fail pharmacotherapy or who not affected by age Risk factors for PE are generally want a permanent solution. Prostheses are either malleable unknown. PE has a detrimental effect on self-confidence (semirigid) or inflatable (two or three piece). Most patients and on relationship with the partner. It may cause mental prefer the three-piece inflatable devices because erections distress, anxiety, embarrassment, and depression; however, are more ‘‘natural,'' but these implants are much more most men with PE do not seek help .
expensive. Satisfaction rates of 70–87% are reported frompatients after appropriate consultation .
Diagnostic work-up The two main complications of penile prosthesis implantation are mechanical failure (<5% after 5-yr follow- Diagnosis of PE is based on the patient's medical and sexual up with currently available three-piece prostheses) and history The history should classify PE as lifelong or infection . With antibiotic prophylaxis, the infection rate acquired and determine whether PE is situational (under is 2–3% and may be further reduced by using an antibiotic- specific circumstances or with a specific partner) or consistent. Special attention should be given to the length requires removing the prosthesis, antibiotic administration, of time of ejaculation, degree of sexual stimulus, impact on and reimplantation after 6–12 mo; however, an 82% success sexual activity and QoL, and drug use or abuse. It is also rate has been achieved using salvage therapy, involving important to distinguish PE from ED.
removal and reimplantation immediately following copious The use of IELT alone is not sufficient to define PE irrigation of the corpora with a multiantibiotic solution .
because there is significant overlap between men with and Although diabetes is considered to be a main risk factor for without PE In everyday clinical practice, self-estimated infection, this association is not supported by current data.
IELT is sufficient. Diagnosis should be multidimensional andshould assess IELT, perceived control, distress, and inter- Premature ejaculation personal difficulty due to ejaculatory dysfunction. The needto assess PE objectively has produced several question- Definition, epidemiology, and risk factors naires, such as the Premature Ejaculation Diagnostic Tool(PEDT) Other questionnaires used to characterise PE There has been difficulty in gaining consensus about how and determine treatment effects include the Premature best to define PE. The Second International Consultation on Ejaculation Profile (PEP) , the Index of Premature Sexual and Erectile Dysfunction has defined PE as ‘‘ejacula- Ejaculation (IPE) , and the Male Sexual Health tion with minimal stimulation and earlier than desired, Questionnaire Ejaculatory Dysfunction (MSHQ-EjD) before or soon after penetration, which causes bother or Currently, their role is optional in everyday clinical practice.
distress, and over which the sufferer has little or no Physical examination includes a brief examination of the voluntary control'' The International Society for Sexual vascular, endocrine, and neurologic systems to identify Medicine has adopted a completely new definition, and the underlying medical conditions associated with PE or other first evidence-based definition, for lifelong PE: ‘‘Premature sexual dysfunctions, such as chronic illness, endocri- ejaculation is a male sexual dysfunction characterised by nopathy, autonomic neuropathy, Peyronie's disease, ure- ejaculation which always or nearly always occurs prior to or thritis, or prostatitis. Laboratory or physiologic testing should within about one minute of vaginal penetration; and inability be directed by specific findings from history or physical to delay ejaculation on all or nearly all vaginal penetrations; examination and is not routinely recommended .
and negative personal consequences, such as distress, bother, A summary of recommendations for the diagnosis of PE frustration and/or the avoidance of sexual intimacy'' . All definitions have taken into account the time to ejaculation,the inability to control or delay ejaculation, and the negative Treatment of premature ejaculation consequences (bother/distress) from PE.
PE may be classified as lifelong (primary) or acquired In many relationships, PE causes few if any problems . In (secondary) . Lifelong PE is characterised by onset from such cases, treatment should be limited to psychosexual the first sexual experience and remains a problem through- counselling. Before beginning treatment, it is essential to out life. Ejaculation occurs too quickly, either before vaginal discuss patient expectations thoroughly. ED or other sexual penetration or <1–2 min afterwards. Acquired PE is char- dysfunction or genitourinary infection (eg, prostatitis) acterised by a gradual or sudden onset, with ejaculation being should be treated first or at the same time as PE.
normal before onset of the problem. Time to ejaculation is Various behavioural techniques have demonstrated short but not usually as fast as in lifelong PE benefit in treating PE. In lifelong PE, behavioural techniques PE is a common male sexual dysfunction, with preva- are not recommended for first-line treatment . They are lence rates of 20–30% . Limited data suggest that the time intensive, require the support of a partner, and can be prevalence of lifelong PE, defined as intravaginal ejaculatory difficult to do.
Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi: EURURO-3367; No. of Pages 11 Table 5 – Recommendations for diagnosis of premature ejaculation (PE) Diagnosis and classification of PE is based on medical and sexual history. It should be multidimensional and should assess IELT, perceived control, distress, and interpersonal difficulty due to the ejaculatory dysfunction.
Clinical use of self-estimated IELT is adequate. Stopwatch-measured IELT is necessary in clinical trials.
Patient-reported outcomes have the potential to identify men with PE. Further research is needed before patient-reported outcomes can be recommended for clinical use.
Physical examination may be necessary in initial assessment of PE to identify underlying medical conditions associated with PE or other sexual dysfunctions, particularly ED.
Routine laboratory or neurophysiologic tests are not recommended. Additional tests should be directed by specific findings from history or physical examination.
ED = erectile dysfunction; LE = level of evidence; GR = grade of recommendation; IELT = intravaginal ejaculatory latency time.
Pharmacotherapy is the basis of treatment in lifelong PE, diffusion of the topical anaesthetic agent into the vaginal but all medical treatments (except dapoxetine in some wall, causing numbness in the partner. In two randomised countries) are off-label indications. Only chronic selective clinical trials, lidocaine-prilocaine cream significantly serotonin reuptake inhibitors (SSRIs) and on-demand topical increased the stopwatch-measured IELT compared to anaesthetic agents have consistently shown efficacy in PE.
placebo . No significant side-effects have been A summary of recommendations for the treatment of PE reported. An aerosol formulation of lidocaine 7.5 mg plus is presented in and a treatment algorithm is given in prilocaine 2.5 mg (Topical Eutectic Mixture for Premature Ejaculation [TEMPE]) is under evaluation and has shownsimilar results SS-cream is a topical anaesthetic agent Psychological and behavioural strategies made from the extracts of nine herbs. It is applied to the Behavioural strategies mainly include the ‘‘stop-start'' glans penis 1 h before intercourse and is washed off programme developed by Semans and its modification, immediately prior to coitus. In a randomised clinical trial, the ‘‘squeeze'' technique, proposed by Masters and Johnson application of 0.2 g of SS-cream significantly improved IELT (several modifications exist) Masturbation before and satisfaction compared with the placebo group anticipation of sexual intercourse is another technique Mild local burning and mild pain were reported by 18.5% of used by many younger men.
patients. No adverse effects on sexual function or on the Success rates of 50–60% have been reported in the short partner were observed, and no systemic side-effects were term A double-blind, randomised, crossover study showed that pharmacologic treatment resulted in greaterIELT prolongation than behavioural therapy Further- Selective serotonin reuptake inhibitors more, clinical experience suggests that improvements Daily SSRIs are the first choice of treatment in PE but are achieved with these techniques are generally not maintained used off label. Commonly used SSRIs include paroxetine in the long term However, there is emerging evidence (20–40 mg/d), sertraline (25–200 mg/d), and fluoxetine that these behavioural psychosexual techniques can be (10–60 mg/d). Based on a systematic review and meta- combined with the pharmaceutical treatments described analysis, SSRIs were expected to increase the geometric below to extend and optimise treatment effects mean IELT by 2.6-fold to 13.2-fold Paroxetine wasfound to be superior to fluoxetine, clomipramine, and Topical anaesthetic agents sertraline. Ejaculation delay may start a few days after drug Lidocaine-prilocaine cream (5%) is applied 20–30 min prior intake, but it is more evident after 1–2 wk and may be to intercourse. Prolonged application of a topical anaes- maintained for several years. Common side-effects of SSRIs thetic agent (30–45 min) may result in loss of erection due include fatigue, drowsiness, yawning, nausea, vomiting, dry to numbness of the penis. A condom is required to avoid mouth, diarrhoea, and perspiration; they are usually mild Table 6 – Recommendations for premature ejaculation (PE) treatment ED, other sexual dysfunction, or genitourinary infection (eg, prostatitis) should be treated first.
Behavioural techniques can benefit PE; however, they are time intensive, require the support of a partner, and can be difficult to do.
Pharmacotherapy is the basis of treatment in lifelong PE Daily SSRIs are first-line, off-label, pharmacologic treatment for PE. The pharmacokinetic profiles of currently available SSRIs are not amenable to on-demand dosing.
Dapoxetine is a short-acting SSRI that has been approved in Europe for the on-demand treatment of PE.
Topical anaesthetic agents provide viable alternatives to SSRIs (off label).
Recurrence is likely after treatment cessation.
Behavioural therapy may augment pharmacotherapy to enhance prevention of relapse.
LE = level of evidence; GR = grade of recommendation; ED = erectile dysfunction; SSRIs = selective serotonin reuptake inhibitors.
Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi:

EURURO-3367; No. of Pages 11 Dapoxetine is a potent SSRI that has been specially designed as an on-demand oral treatment for PE. Anintegrated analysis of two randomised clinical trialsreported that dapoxetine, 30 and 60 mg, improved IELTsignificantly compared with placebo Improved ejacu-lation control was reported by 51% and 58% of patients inthe 30-mg and 60-mg dosage groups, respectively. Bothdapoxetine doses were effective on the first dose. In anotherrandomised clinical trial, the mean average IELT increasedfrom 0.9 min at baseline (all groups) to 1.9 min, 3.2 min, and3.5 min with placebo and dapoxetine 30 mg and dapoxetine60 mg, respectively The geometric mean IELT in-creased from 0.7 min at baseline to 1.1 min, 1.8 min, and2.3 min, respectively ( p < 0.001). The most commonadverse events were nausea (16.5–30.6%), dizziness(7.7–13.4%), diarrhoea (3.9–11.3%), and headache (6.4–13.6%). However, these adverse events led to discontinua-tion in only 1.3%, 3.9%, and 8.2% of subjects with placebo,dapoxetine 30 mg, and dapoxetine 60 mg, respectively.
Dapoxetine has been approved (December 2008) for thetreatment of PE in seven European countries (Sweden,Austria, Finland, Germany, Spain, Italy, and Portugal).
Phosphodiesterase type 5 inhibitors Several recent studies have supported the therapeutic roleof PDE5-Is in PE; however, only one randomised clinical trialcompares sildenafil to placebo Although IELT was notsignificantly improved, sildenafil increased confidence, theperception of ejaculatory control, and overall sexualsatisfaction as well as reduced anxiety and decreased therefractory time to achieve a second erection after ejacula-tion.
In another randomised clinical trial, lidocaine-prilocaine monotherapy showed similar efficacy to that of combina-tion with sildenafil, while the efficacy of sildenafil alone wassimilar to placebo In another study, sildenafilsignificantly improved IELT and satisfaction and reducedoverall anxiety compared with several SSRIs and the‘‘pause-squeeze'' technique . Several open-label studiesfound that sildenafil combined with an SSRI is superior toSSRI monotherapy.
ED and PE are the two most common male sexualdysfunctions. PDE5-Is are the first-line treatment optionfor ED, whereas SSRIs represent the most efficacioustreatment option for PE. Physicians should identify patients' Fig. 3 – Management of premature ejaculation (PE) provided separately.
needs and expectations and adapt treatment accordingly.
IELT = intravaginal ejaculatory latency time; ED = erectile dysfunction;SSRIs = selective serotonin reuptake inhibitors.
This summary of the EAU guidelines provides the frame-work for diagnosis and treatment of ED and PE in clinicalpractice.
and gradually improve after 2–3 wk. Decreased libido,anorgasmia, anejaculation, and ED have been also reported.
Author contributions: Konstantinos Hatzimouratidis and Eric Wespes On-demand treatment is inferior to daily dosing but may be had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
combined with an initial trial of daily treatment orconcomitant low-dose daily treatment to reduce adverse Study concept and design: Hatzimouratidis, Amar, Eardley, Giuliano, Hatzichristou, Montorsi, Vardi, Wespes.
Please cite this article in press as: Hatzimouratidis K, et al. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction andPremature Ejaculation. Eur Urol (2010), doi: EURURO-3367; No. of Pages 11 erectile dysfunction: results of a multicenter, randomized, double- Hatzichristou, Montorsi, Vardi, Wespes.
blind, placebo-controlled trial. Eur Urol 2006;50:351–9.
Analysis and interpretation of data: Hatzimouratidis, Amar, Eardley, [15] Rajfer J, Aliotta PJ, Steidle CP, Fitch III WP, Zhao Y, Yu A. Tadalafil Giuliano, Hatzichristou, Montorsi, Vardi, Wespes.
dosed once a day in men with erectile dysfunction: a randomized, Drafting of the manuscript: Hatzimouratidis.
double-blind, placebo-controlled study in the US. Int J Impot Res Critical revision of the manuscript for important intellectual content: Hatzimouratidis, Amar, Eardley, Giuliano, Hatzichristou, Montorsi, Vardi, [16] Hatzichristou D, Gambla M, Rubio-Aurioles E, et al. Efficacy of tadalafil once daily in men with diabetes mellitus and erectile Statistical analysis: None.
dysfunction. Diabet Med 2008;25:138–46.
Obtaining funding: None.
[17] Vlachopoulos C, Ioakeimidis N, Rokkas K, Stefanadis C. Cardiovascu- Administrative, technical, or material support: Hatzimouratidis.
lar effects of phosphodiesterase type 5 inhibitors. J Sex Med 2009;6: Other (specify): None.
[18] Zumbe´ J, Porst H, Sommer F, Grohmann W, Beneke M, Ulbrich E.
Comparable efficacy of once-daily versus on-demand vardenafil in Financial disclosures: I certify that all conflicts of interest, including men with mild-to-moderate erectile dysfunction: findings of the specific financial interests and relationships and affiliations relevant RESTORE study. Eur Urol 2008;54:204–12.
to the subject matter or materials discussed in the manuscript [19] Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H. Randomized (eg, employment/affiliation, grants or funding, consultancies, honoraria, study of testosterone gel as adjunctive therapy to sildenafil in stock ownership or options, expert testimony, royalties, or patents filed, hypogonadal men with erectile dysfunction who do not respond received, or pending), are the following: None.
to sildenafil alone. J Urol 2004;172:658–63.
Funding/Support and role of the sponsor: None.
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