Yoram Vardi

Summary of the recommendations on sexual dysfunctions in men

INTRODUCTIONnSexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being.nnnAIMnTo provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men.nnnMETHODSnAn international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures.u2002 New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations.nnnRESULTSnAlgorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to mens and womens individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronies disease; and priapism.nnnCONCLUSIONSnSexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

Guidelines on Male Sexual Dysfunction: Erectile Dysfunction and Premature Ejaculation

CONTEXTnErectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male sexual dysfunctions.nnnOBJECTIVEnTo present the updated version of 2009 European Association of Urology (EAU) guidelines on ED and PE.nnnEVIDENCE ACQUISITIONnA 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 assigned.nnnEVIDENCE SYNTHESISnED is highly prevalent, and 5-20% of men have moderate to severe ED. ED shares common risk factors with cardiovascular disease. Diagnosis is based on medical and sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to the patients 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 for patients who do not respond to PDE5-Is or for whom PDE5-Is are contraindicated include intracavernous injections, intraurethral alprostadil, vacuum constriction devices, or implantation of a penile prosthesis. 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 the on-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.nnnCONCLUSIONSnThese EAU guidelines summarise the present information on ED and PE. The extended version of the guidelines is available at the EAU Web site (http://www.uroweb.org/nc/professional-resources/guidelines/online/).

Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection.

Relaxation of the trabecular smooth muscle of the corpus cavernosum (the erectile tissue) of the penis is mediated by nitric oxide released by the nerves and endothelium. We have investigated the physiological role of oxygen tension in the regulation of trabecular smooth muscle tone. In human subjects, measurement of intracavernosal PO2 in blood drawn from corpus cavernosum in the flaccid state was comparable to that of venous blood (25-43 mmHg). Vasodilatation of the resistance arteries and trabecular smooth muscle relaxation by intracavernosal injection of papaverine and phentolamine caused oxygen tension to rise rapidly to arterial levels (PO2 approximately 100 mmHg). Isolated human and rabbit corpus cavernosum tissue strips in organ baths, exposed to arterial-like PO2 relaxed to the endothelium-dependent dilator acetylcholine and to electrical stimulation of the autonomic dilator nerves. These nitric oxide-mediated responses were progressively inhibited as a function of decreasing PO2 to levels measured in the flaccid penis. Reverting to normoxic conditions readily restored endothelium-dependent and neurogenic relaxation. Relaxation to exogenous nitric oxide was not impaired in low PO2. In rabbit corpus cavernosum, low PO2 reduced basal levels of cGMP and prevented cGMP accumulation induced by stimulation of dilator nerves. Furthermore, low PO2 inhibited nitric oxide synthase activity in corpus cavernosum cytosol. It is concluded that physiological concentrations of oxygen modulate penile erection by regulating nitric oxide synthesis in corpus cavernosum tissue.

Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction.

BACKGROUNDnLow-intensity extracorporeal shockwave therapy (LI-ESWT) is currently under investigation regarding its ability to promote neovascularization in different organs.nnnOBJECTIVEnTo evaluate the effect of LI-ESWT on men with erectile dysfunction (ED) who have previously responded to oral phosphodiesterase type 5 inhibitors (PDE5-I).nnnDESIGN, SETTING, AND PARTICIPANTSnWe screened 20 men with vasculogenic ED who had International Index of Erectile Function ED (IIEF-ED) domain scores between 5-19 (average: 13.5) and abnormal nocturnal penile tumescence (NPT) parameters. Shockwave therapy comprised two treatment sessions per week for 3 wk, which were repeated after a 3-wk no-treatment interval.nnnINTERVENTIONnLI-ESWT was applied to the penile shaft and crura at five different sites.nnnMEASUREMENTSnAssessment of erectile function was performed at screening and at 1 mo after the end of the two treatment sessions using validated sexual function questionnaires, NPT parameters, and penile and systemic endothelial function testing. The IIEF-ED questionnaire was answered at the 3- and 6-mo follow-up examinations.nnnRESULTS AND LIMITATIONSnWe treated 20 middle-aged men (average age: 56.1 yr) with vasculogenic ED (mean duration: 34.7 mo). Eighteen had cardiovascular risk factors. At 1 mo follow-up, significant increases in IIEF-ED domain scores were recorded in all men (20.9 +/- 5.8 vs 13.5+/- 4.1, p<0.001); these remained unchanged at 6 mo. Moreover, significant increases in the duration of erection and penile rigidity, and significant improvement in penile endothelial function were demonstrated. Ten men did not require any PDE5-I therapy after 6-mo follow-up. No pain was reported from the treatment and no adverse events were noted during follow-up.nnnCONCLUSIONSnThis is the first study that assessed the efficacy of LI-ESWT for ED. This approach was tolerable and effective, suggesting a physiologic impact on cavernosal hemodynamics. Its main advantages are the potential to improve erectile function and to contribute to penile rehabilitation without pharmacotherapy. The short-term results are promising, yet demand further evaluation with larger sham-control cohorts and longer follow-up.

Normative values for female genital sensation.

OBJECTIVESnNeurologic disorders might be responsible for many cases of female sexual dysfunction. Yet, they are currently undiagnosed because of the lack of measurement tools to assess genital neural function. Therefore, our objective is to provide norms for sensory thresholds in the vagina and clitoris, for a wide range of patient ages.nnnMETHODSnVaginal and clitoral warm, cold, and vibratory sensory thresholds were measured in 89 healthy paid volunteers by the method of limits. Normograms were derived from this group of healthy volunteers. An additional 61 patients were also tested, for a total of 150 individuals. Sixty-two individuals (42 healthy volunteers and 20 patients) from the total group were tested twice to provide test-to-test repeatability data across the range of clinical (normal and abnormal) responses.nnnRESULTSnNormograms are presented, providing age-corrected upper and lower normal values, expressed as 95% confidence limits for warm, cold, and vibratory thresholds. Intertest repeatability is also reported.nnnCONCLUSIONSnThermal and vibratory thresholds of both the vaginal and clitoral region are clinically feasible, valid, and repeatable. These can be applied as a valuable diagnostic tool to assess neural dysfunction through sensory assessment of the female genitalia.

Vulvar vestibulitis severity—assessment by sensory and pain testing modalities

&NA; Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre‐menopausal women. Previous quantitative sensory test (QST) studies have demonstrated reduced vestibular pain thresholds in these patients. Here we try to find whether QST findings correlate to disease severity. Thirty‐five vestibulitis patients, 17 with moderate and 18 with severe disorder, were compared to 22 age matched control women. Tactile and pain thresholds for mechanical pressure and thermal pain were measured at the posterior fourcette. Magnitude estimation of supra‐threshold painful stimuli were obtained for mechanical and thermal stimuli, the latter were of tonic and phasic types. Pain thresholds were lower and supra‐threshold magnitude estimations were higher in VVS patients, in agreement with disease severity. Cut‐off points were defined for results of each test, discriminating between moderate VVS, severe VVS and healthy controls, and allowing calculation of sensitivity and specificity of the various tests. Our findings show that the best discriminative test was mechanical pain threshold obtained by a simple custom made ‘spring pressure device’. This test had the highest &kgr; value (0.82), predicting correctly 88% of all VVS cases and 100% of the severe VVS cases. Supra‐threshold pain magnitude estimation for tonic heat stimulation also had a high &kgr; value (0.73) predicting correctly 82% overall with a 100% correct diagnosis of the control group. QST techniques, both threshold and supra‐threshold measurements, seem to be capable of discriminating level of severity of this clinical pain syndrome.

Can stronger pelvic muscle floor improve sexual function

Introduction and hypothesisThis study aims to evaluate the association between pelvic floor muscle (PFM) strength and sexual functioning.MethodsRetrospective chart review of consecutive all women who were referred with a primary complaint of sexual dysfunction. Women underwent standardized clinical evaluation including pelvic muscle strength which was ranked from 0 (weak) to 2 (strong). The duration of pelvic muscle contraction was also recorded in seconds. Sexual function was evaluated by using a validated questionnaire, the Female Sexual Function Index (FSFI).ResultsOne hundred seventy-six women with a mean age of 37u2009±u200911xa0years were included. Women with strong or moderate PFM scored significantly higher on the FSFI orgasmic and arousal domains than women with weak PFM (5.4u2009±u20090.8 vs. 2.8u2009±u20090.8, and 3.9u2009±u20090.5 vs. 1.7u2009±u20090.24, respectively; Pu2009<u20090.001). The duration of PFM contraction was correlated with FSFI orgasmic domain and sexual arousal (ru2009=u20090.26, Pu2009<u20090.001; ru2009=u20090.32, Pu2009<u20090.0001, respectively).ConclusionsOur findings suggest that both the orgasm and arousal function are related to better PFM function.

Penile and Systemic Endothelial Function in Men with and without Erectile Dysfunction

BACKGROUNDnAssessment of endothelial function can provide essential information about the mechanisms of cardiovascular disease. Emerging data show that erectile dysfunction (ED) can precede the symptoms of ischemic heart disease, and this suggests that endothelial dysfunction is the link between these two clinical entities.nnnOBJECTIVEnTo evaluate penile and systemic endothelial function in subjects with and without ED.nnnDESIGN, SETTING, AND PARTICIPANTSnFifty-nine subjects were enrolled in the study. According to their International Index of Erectile Function (IIEF) ED domain scores, they were divided into two groups: 40 patients with ED and 19 men without ED (control group). Hemodynamic measurements, penile endothelial function, and forearm endothelial function were assessed in all participants using veno-occlusive plethysmography.nnnMEASUREMENTSnWe measured baseline blood flow in both the forearm and the penis and calculated the corresponding vascular resistances. Postischemic changes in blood flow were recorded serially in both organs for the evaluation of endothelial function. Area under the flow-time curve (AUC), and maximal blood flow after ischemia were considered to be the indices of endothelial function.nnnRESULTS AND LIMITATIONSnGeneral characteristics of the two groups of participants were comparable except for age (40.5+/-3.3 yr in the control group vs 53.3+/-2.3 yr in the ED group). Baseline forearm blood flow was similar in the two groups, but the penile blood flow was significantly lower in men with ED compared with that in the men without ED: 6.2+/-0.6 versus 8.6+/-0.6 ml/min per 100ml of tissue (p=0.006). Penile vascular resistance was higher in the ED group compared with the control group. The indices of forearm endothelial function were comparable in both groups (p=0.70 for the AUCs). However, indices of penile endothelial function were significantly higher in the control group compared with those of the ED group (AUC: 950 units+/-130 vs 450+/-80 units, p=0.001).nnnCONCLUSIONSnThe use of veno-occlusive plethysmography for evaluating penile endothelial function is simple and reliable and provides new information on the pathophysiology of ED at the level of penile vasculature. This is the first study that provides evidence of impaired penile endothelial function without the presence of a significant peripheral endothelial dysfunction. Furthermore, these results provide further support for the notion that the development of ED could predict the future onset of cardiovascular disease.

Who's Afraid of the G‐spot?

INTRODUCTIONnNo controversy can be more controversial than that regarding the existence of the G-spot, an anatomical and physiological entity for women and many scientists, yet a gynecological UFO for others.nnnMETHODSnThe pros and cons data have been carefully reviewed by six scientists with different opinions on the G-spot. This controversy roughly follows the Journal of Sexual Medicine Debate held during the International Society for the Study of Womens Sexual Health Congress in Florence in the February of 2009.nnnMAIN OUTCOME MEASUREnTo give to The Journal of Sexual Medicines reader enough data to form her/his own opinion on an important topic of female sexuality.nnnRESULTSnExpert #1, who is JSMs Controversy section editor, reviewed histological data from the literature demonstrating the existence of discrete anatomical structures within the vaginal wall composing the G-spot. He also found that this region is not a constant, but can be highly variable from woman to woman. These data are supported by the findings discussed by Expert #2, dealing with the history of the G-spot and by the fascinating experimental evidences presented by Experts #4 and #5, showing the dynamic changes in the G-spot during digital and penile stimulation. Experts #3 and #6 argue critically against the G-spot discussing the contrasting findings so far produced on the topic.nnnCONCLUSIONnAlthough a huge amount of data (not always of good quality) have been accumulated in the last 60 years, we still need more research on one of the most challenging aspects of female sexuality.

Standards for Clinical Trials in Male Sexual Dysfunctions

INTRODUCTIONnClinical trials in male sexual dysfunction (MSD) are expanding. Consequently, there is a need for consensus standards in this area.nnnAIMnTo develop an evidence-based, state-of-the-art consensus report on standards for clinical trials in MSD.nnnMETHODSnA literature review was performed examining clinical trials in erectile dysfunction (ED), premature ejaculation (PE), delayed/absent ejaculation, libido disorders/loss of desire, hypogonadism, and Peyronies disease, focusing on publications published in the last 20 years. This manuscript represents the opinions of eight experts from seven countries developed in a consensus process. This document was presented for peer review and debate in a public forum and revisions were made based on recommendations of chairpersons to the International Consultation on Sexual Medicine.nnnMAIN OUTCOME MEASUREnExpert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.nnnRESULTSnAccording to experience and recent publications in dealing with clinical trials in sexual dysfunction, recommendations have been made for conducting trials in patients with ED, PE, delayed ejaculation, libido disorders, hypogonadism, and Peyronies disease.nnnCONCLUSIONSnIt is important that future clinical trials are conducted using standards upon which investigators can rely when reading manuscripts or conducting new trials in this field.