A comprehensive history of injection therapy for erectile dysfunction, 1982-2023.

INTRODUCTION: Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982. OBJECTIVES: To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy. METHODS: Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed. RESULTS: The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine. CONCLUSIONS: After 40 years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.

The Lost Penis Syndrome: A New Clinical Entity in Sexual Medicine.

INTRODUCTION: The "lost penis syndrome" (LPS) is a term often used in non-clinical settings to describe the subjective perception of the loss of cutaneous and proprioceptive feelings of the male organ during vaginal penetration. Although deserving clinical attention, this syndrome did not receive any consideration in the medical literature. Notwithstanding, it represents a relatively unexceptional condition among patients in sexual medicine clinics, and it is often reported together with other sexual dysfunctions, especially delayed ejaculation, anejaculation, male anorgasmia and inability to maintain a full erection. OBJECTIVES: To draft a new conceptual characterization of the LPS, defined as a lack of penile somesthetic sensations during sexual penetration due to various causes and leading to several sexual consequences in both partners. METHODS: Based on an extensive literature review and physiological assumptions, the mechanisms contributing to friction during penovaginal intercourse, and their correlation to LPS, have been explored, as well as other nonanatomical factors possibly contributing to the loss of penile sensations. RESULTS: Efficient penile erection and sensitivity, optimal vaginal lubrication and trophism contribute to penovaginal friction. Whenever one of these processes does not occur, loss of penile sensation defined as LPS can occur. Sociocultural, psychopathological and age-related (ie, couplepause) factors are also implicated in the etiology. Four types of LPS emerged from the literature review: anatomical and/or functional, behavioral, psychopathological and iatrogenic. According to the subtype, a wide variety of treatments can be employed, including PDE5i, testosterone replacement therapy and vaginal cosmetic surgery, as well as targeted therapy for concomitant sexual comorbidity. CONCLUSION: We held up the mirror on LPS as a clinically existing multifactorial entity and provided medical features and hypotheses contributing to or causing the occurrence of LPS. In the light of a sociocultural and scientific perspective, we proposed a description and categorization of this syndrome hypothesizing its usefulness in daily clinical practice. Colonnello E, Limoncin E, Ciocca G, et al. The Lost Penis Syndrome: A New Clinical Entity in Sexual Medicine. Sex Med Rev 2022;10:113-129.

Review of the Current Status of Low Intensity Extracorporeal Shockwave Therapy (Li-ESWT) in Erectile Dysfunction (ED), Peyronie's Disease (PD), and Sexual Rehabilitation After Radical Prostatectomy With Special Focus on Technical Aspects of the Different Marketed ESWT Devices Including Personal Experiences in 350 Patients.

INTRODUCTION: Although the literature of the positive effects of penile low intensity extracorporeal shockwave therapy is meanwhile substantial, there are substantial differences regarding both the sources of energies and extracorporeal shockwave therapy (ESWT) devices. OBJECTIVES: To provide an overview on the energy range and energy differences of the 6 currently marketed ESWT devices along with personal ESWT experiences in 350 patients. METHODS: This review includes all published preclinical and clinical penile ESWT studies with evaluation of the technical differences of the 6 ESWT devices and the personal experiences with these 6 devices in ED and PD. The main outcomes measures were success rates in ED (International Index of Erectile Function-erectile function change, conversion of phosphodiesterase type 5 inhibitors non-responders) and PD (change in deviation and plaque size), differences of used sources of energy, and energy flux densities (EFDs). RESULTS: 3 different sources of energies are used, that is electromagnetic, electrohydraulic, and piezoelectric .The devices markedly distinguish in the available spectrum of the EFD ranging between 0.09 and 0.55 mJ/mm². In terms of the biological effects, the relevant energy parameters are -6 dB and the 5 MPa focus, which differ substantially between the ESWT devices. In addition, a great variability in the treatment protocols and applied energy is obvious. The preliminary own experiences with low intensity extracorporeal shockwave therapy in 160 ED non-responders and 190 patients with PD with success rates of 45% and 47%, respectively, are reported. CONCLUSION: Positive results were published with all 6 ESWT devices in question in patients with organic ED but with huge differences regarding the EFD and the total energies applied. There is growing evidence that concentrated treatment protocols and increasing energies may yield better results. In this context, it may be argued that at least some of the published studies were markedly underpowered .Owing to the paucity of published studies, the literature of the effects of ESWT in PD and for penile rehabilitation after pelvic surgery is currently not conclusive. Porst H. Review of the Current Status of Low Intensity Extracorporeal Shockwave Therapy (Li-ESWT) in Erectile Dysfunction (ED), Peyronie's Disease (PD), and Sexual Rehabilitation After Radical Prostatectomy With Special Focus on Technical Aspects of the Different Marketed ESWT Devices Including Personal Experiences in 350 Patients. Sex Med 2021;9:93-122.

[Reflexions on 50 Years of Sexual Medicine in Urology Focusing on Male Sexual Dysfunctions]. / Reflexionen über 50 Jahre Sexualmedizin in der Urologie mit Fokus auf männliche Sexualstörungen.

Diagnosis and therapy of male sexual dysfunctions made enormous progress over the last 50 years. Starting with the development of hydraulic penile implants in 1973 meanwhile several effective and well-tolerated conservative treatments such as the PDE-5 inhibitors avanafil, sildenafil, tadalafil and vardenafil, transurethral PGE1 (MUSE) and self-injection therapy with a variety of vasoactive drugs like alprostadil, papaverine/phentolamine (bimix), PGE1/papaverine/phentolamine (trimix/triple drug) or VIP (aviptadil)/phentolamine-Invicorp) have been developed for the treatment of ED. More recently Li-ESWT has provided impressive results both in PDE-5i responders and non-responders and partly also in Peyronie's disease. Regarding premature ejaculation (PE) meanwhile with oral dapoxetine and topical lidocaine/prilocaine spray two effective treatment options are officially available which may be combined in men with severe PE and with PDE-5 inhibitors in men with PE and ED. Hormonal disorders such as hypogonadism, hyperprolactinemia and thyroid disorders may be linked to male sexual disorders and successfully treated with T-substitution, prolactin inhibitors or thyroid specific medications.Whereas vascular surgery for ED such as deep dorsal vein ligation/resection or arterial revascularization procedures dominated the 80ies and 90ies last century they have been considered outdated and are replaced in severe ED of organic etiology by the modern new three piece inflatable penile implants whose high technical standard meanwhile provide 10 years survival rates of about 70 %.

Current Strategies in the Management of Peyronie's Disease (PD)-Results of a Survey of 401 Sexual Medicine Experts Across Europe.

INTRODUCTION: Peyronie's disease (PD) is a progressive and devastating penile disorder that often results in severe penile curvature with penile shrinking, making vaginal insertion difficult or even impossible. Until now, in contrast to other penile disorders such as erectile dysfunction, PD is characterized by a paucity of conservative treatment options. AIM: To investigate the current status quo in the management of PD across European experts in sexual medicine. METHODS: Members of the European Society of Sexual Medicine and of various andrology and urology societies across Europe, with the majority (78%) being urologists, were contacted via e-mail and newsletters and asked to fill in an online questionnaire. The survey comprised 56 items developed by an expert consensus of the educational committee of the European Society of Sexual Medicine. In the end, 401 participants responded to the entire survey, with 277 reporting treating PD patients themselves and knowing this penile entity very well. MAIN OUTCOME MEASURES: Main outcome measures include description of current strategies regarding diagnosis and treatment of PD as reported by specialists in this field. RESULTS: Of the physicians treating PD patients, 94% performed penile palpation, and 74% perform ultrasonography. 45% assessed the degree of penile curvature by means of intravenous drug testing, but only 17% measured it accurately with a goniometer. Penile length, flaccid or in erect state, was measured by only 39% or 25%, respectively. Only 45% assessed testosterone. Primary treatment options were oral (65%), counseling (57%), and topical/local therapy (30%). Among oral drug users, tadalafil 5 mg was the most commonly used (57%), followed by vitamin E (40%). Regarding intralesional therapy, collagenase clostridium histolyticum was the leading drug (34%), followed by calcium channel blockers (17%). Considering surgical procedures, the original Nesbit technique was the preferred procedure (33%). 36% of the specialists expressed their dissatisfaction with the currently available treatment options, and 64% reported the impression that their patients were mostly dissatisfied with the treatment outcomes. CLINICAL IMPLICATIONS: Innovative and presumably multi-modal treatment protocols for PD are urgently needed. STRENGTHS & LIMITATIONS: The survey represents 1 of the largest studies on the management of PD. The results are representative for the standard management of PD mostly among European Urologists with specialization in sexual medicine and may therefore not be generalizable to regions outside Europe or to other physicians treating PD. CONCLUSION: Around one-third of experts and, from their perspective, around two-thirds of patients are dissatisfied with the currently available PD treatment options. Porst H, Burri A, the European Society for Sexual Medicine (ESSM) Educational Committee. Current Strategies in the Management of Peyronie's Disease (PD)-Results of a Survey of 401 Sexual Medicine Experts Across Europe. J Sex Med 2019;16:901-908.

Novel Treatment for Premature Ejaculation in the Light of Currently Used Therapies: A Review.

INTRODUCTION: Besides erectile dysfunction, premature ejaculation (PE) is the most frequent male sexual disorder and shows a high level of bother and distress. The negative consequences of long-term and unsuccessfully treated PE on both patient and partner are well established in the literature and include personal distress, impairment of the partner's sexual function, and interpersonal difficulties. AIM: To outline the consequences of untreated PE and the advantages and disadvantages of currently available treatment options with a special focus on a new topical eutectic lidocaine/prilocaine metered dose spray (Fortacin; Lidocaine/Prilocaine, Recordati, Milan, Italy) which represents the second officially approved drug in this indication. METHODS: Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases such as Web of Science, Medline, PubMed, and Google Scholar, hand searches, and authoritative texts. Combinations of keywords including premature ejaculation, ejaculatory control, intravaginal ejaculation latency time, IELT, PE, PDE5 inhibitors (PDE5i), SSRIs, topical anesthetics, lidocaine, prilocaine, and treatment were used. In the end, 59 studies published between 2000 and 2018 were considered relevant for this review. MAIN OUTCOME MEASURES: Published studies on PE-related negative psychosocial outcomes, as well as advantages and disadvantages of currently available off-label and officially approved treatment options. RESULTS: Although a variety of treatment options for PE have shown marked improvements in stopwatch-measured intravaginal ejaculation latency time (IELT) and patient-reported outcomes as assessed by the Premature Ejaculation Profile (PEP), none of the investigated drugs has reached market approval. The only so far officially approved medication-dapoxetine-is characterized by high discontinuation rates of up to 90%, mostly because of high side effects, cost issues, efficacy below expectations, and the need for scheduling sexual intercourse. CONCLUSION: With the official approval in Europe the new dose-metered lidocaine-prilocaine spray (Fortacin) may become a real first-line therapy option for PE and may offer a satisfactory and affordable solution, especially because of its unique galenic preparation, making its handling easy and customer friendly. In addition, it has the potential to significantly increase the currently low patients' acceptance of available monotherapies and become an established second-line therapy for the severe PE patients with IELTs <1 to 2 minutes or with ante-portal ejaculation in combination with oral therapy. Porst H, Burri A. Novel treatment for premature ejaculation in the light of currently used therapies: A review. Sex Med Rev 2019; 7:129-140.

Penile traction therapy with the new device 'Penimaster PRO' is effective and safe in the stable phase of Peyronie's disease: a controlled multicentre study.

OBJECTIVES: To evaluate the efficacy and safety of a new penile traction device (PTD), 'Penimaster PRO', in a group of patients with stable Peyronie's disease (PD) compared with a non-intervention group in a multicentre study. MATERIAL AND METHODS: A total of 93 patients with chronic stable PD (without erectile dysfunction, with no significant pain, and with a unidirectional curvature of at least 45° being stable for > 3 months) were recruited and followed for a 12-week period. Of these patients, 47 were randomly assigned to the Penimaster PRO group (PG) and 46 to the non-intervention group (NIG). Patients were asked to apply the PTD 3-8 h a day for 12 consecutive weeks, with specific instructions regarding the progressive increase of traction force applied to the penis over time. The primary outcome of the study was the change in the degree of curvature measured in the fully erect state after intracavernosal injection of alprostadil at baseline, 1, 2 and 3 months. Other variables, such as the type of curvature, stretched penile length (SPL), Peyronie's Disease Questionnaire (PDQ) scores, erectile function domain of the International Index of Erectile function (IIEF-EF) score and adverse events (AEs) were also assessed in each visit. RESULTS: Forty-one patients in the PG and 39 in the NIG completed the study. There was an overall reduction in curvature of 31.2° (P < 0.001) at 12 weeks compared to baseline in the PG, representing a 41.1% improvement from baseline, which significantly correlated with the number of daily hours the device was applied in a dose-dependent manner. Those patients using the device < 4 h/day experienced a reduction of 15°-25° (mean 19.7°, 28.8% improvement; P < 0.05), while patients using the device > 6 h/day experienced greater curvature reduction, ranging from 20° to 50° (mean of 38.4°, 51.4% improvement; P < 0.001). In contrast, no significant changes in curvature were observed in the NIG. Furthermore, SPL increased significantly in the PG compared to baseline and compared with the NIG, ranging from 0.5 to 3.0 cm (mean 1.8 cm; P < 0.05). The IIEF-EF score also improved in patients in the PG (by a mean of 5 points). Mild AEs occurred in 43% of patients, such as local discomfort and glans numbness. CONCLUSION: The use of the Penimaster PRO PTD, a non-invasive treatment, should be offered to patients with stable PD for 3 consecutive months before performing any corrective surgery, as this provided a significant reduction in the curvature, an increase in penile length and a significant improvement of the symptoms and bother induced by PD.

The Importance of Male Ejaculation for Female Sexual Satisfaction and Function.

INTRODUCTION: Although links between ejaculatory control or intravaginal ejaculatory latency time and female sexual functioning have frequently been reported in the past, no study has investigated the importance of other male ejaculatory characteristics, such as ejaculation volume and intensity, for women's sexuality. AIM: To assess the importance of subjectively perceived ejaculation intensity and ejaculation volume for female sexual function and satisfaction. METHODS: This was a cross-sectional online survey including 240 sexually active, heterosexual women (median age 27.4 years), using study-specific questions and validated questionnaires. MAIN OUTCOME MEASURE: Results are presented as means, percentages, and age-controlled partial correlation coefficients of the main study variables. RESULTS: 50.43% of women considered it very important that the partner ejaculates during intercourse. 18.3% of women preferred that the partner ejaculates before they reach orgasm, whereas for 53.5% this did not matter. 22.6% of women stated that they experienced a more intense orgasm when their partner ejaculated during vaginal intercourse. 17.4% reported that they definitely experienced a more intensive orgasm depending on the intensity of their partner's ejaculation, whereas for 17.8% this did not matter at all. 20.9% of women did not feel that their orgasm was more intense depending on the subjectively felt ejaculate quantity, whereas the majority (37.9%) stated that it did not matter. 13.1% of women regarded the quantity of expelled ejaculate as an expression of their own sexual attractiveness. Women stating that they experienced more intense orgasms when the partner ejaculated, when the partner experienced a more intense ejaculation, and when he expelled a greater ejaculate quantity also reported better lifelong orgasmic function (r = 0.24, r = 0.15, r = .26, respectively) and more lifelong sexual satisfaction (r = .29, r = .15, r = 26, respectively). CLINICAL IMPLICATIONS: The perception of ejaculatory characteristics can be related to the female partner's sexual satisfaction and overall sexual functioning. STRENGTH & LIMITATIONS: This is the very first study to explore the importance of male ejaculation volume and intensity for women's sexual functioning. Data are of self-report nature and ejaculation characteristics were not objectively measured but by women's self-report. CONCLUSION: Although male ejaculation and its different aspects seem to play an important role for women, the study demonstrates a considerable variability of women's attitudes toward ejaculatory characteristics. Further research is required to examine the sources of this variability. Burri A, Buchmeier J, Porst H. The importance of male ejaculation for female sexual satisfaction and function. J Sex Med 2018;15:1600-1608.

The relationship between penile deformity, age, psychological bother, and erectile dysfunction in a sample of men with Peyronie's Disease (PD).

The aim of the present study was to investigate which PD specific factors (e.g., degree of penile curvature, levels of pain) cause most distress and to further explore whether there are specific subgroups of patients that report particularly high levels of psychological distress. Data were available for N = 119 men with a clinical diagnosis of PD presenting at a private Uro-Andrology in Germany. The strongest complaint of men with PD was being bothered by the look of the penis as opposed to being distressed by the pain (3.48 vs. 2.11). 75.4% reported having significantly less intercourse due to PD and for 61.4% this was very bothersome. Plaque size correlated positively with the level of symptom bother (r = 0.73, p < 0.05). Furthermore, men with a stronger curvature reported more concerns regarding size and form of the penis (r = 0.18, p < 0.05), more overall sexual dissatisfaction (r = -0.38, p < 0.001), and more PD related psychological and physiological symptoms (r = 0.58, p < 0.001). 44.4% of patients had a concurrent ED. Highest level of symptom bother was reported by men with a a strong curvature and a comorbid ED. Clinicians should pay special attention to patients presenting with extreme penile deformity and impaired sexual functioning, as they show the highest levels of psychological distress. Here, additional psychosexual support might be necessary.

Preliminary Validation of a German Version of the Sexual Complaints Screener for Women in a Female Population Sample.

BACKGROUND: To date, neither the original English nor any of the translated versions of the Sexual Complaints Screener for Women (SCS-W) have been tested for their psychometric properties. AIM: To evaluate the validity and utility of the German version of the SCS-W by assessing content, convergent, and discriminant validity. METHODS: A population sample of 309 women (mean age = 26.9 years) completed the online survey and had matching data available on the SCS-W and the Female Sexual Function Index (FSFI). Spearman bivariate correlations between the SCS-W and FSFI domain scores and exploratory factor analysis with principal component analysis were conducted. OUTCOMES: Convergent validity was excellent for the domain of orgasm, good for satisfaction, dyspareunia, and the total questionnaire score, and acceptable for desire, lubrication, arousal, and vaginismus. Discriminant validity was present for all domains apart from arousal, lubrication, and vaginismus. Varimax rotation suggested an 8-factor model was the most robust. CLINICAL IMPLICATIONS: This brief screener seems suitable to provide a brief overview of female patients' sexual problems in a clinical setting. STRENGTHS AND LIMITATIONS: This is the 1st study to assess the psychometric properties of the German version of the SCS-W. However, available information on the psychometric properties of the German SCS-W was limited because the validity of the screener could not be counterchecked against a clinical diagnosis of female sexual dysfunction. CONCLUSION: Our results provide preliminary evidence of good validity of the German version of the SCS-W. Overall, the SCS-W can offer support for clinicians who are less familiar with sexual medicine and who might not routinely discuss sexual issues with their patients. Burri A, Porst H. Preliminary Validation of a German Version of the Sexual Complaints Screener for Women in a Female Population Sample. Sex Med 2018;6:123-130.

Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME).

BACKGROUND: The benefits and risks of long-term testosterone administration have been a topic of much scientific and regulatory interest in recent years. AIM: To assess long-term quality of life (QOL) and sexual function benefits of testosterone replacement therapy (TRT) prospectively in a diverse, multinational cohort of men with hypogonadism. METHODS: A multinational patient registry was used to assess long-term changes associated with TRT in middle-age and older men with hypogonadism. Comprehensive evaluations were conducted at 6, 12, 24, and 36 months after enrollment into the registry. OUTCOMES: QOL and sexual function were evaluated by validated measures, including the Aging Males' Symptom (AMS) Scale and the International Index of Erectile Function (IIEF). RESULTS: A total of 999 previously untreated men with hypogonadism were enrolled at 25 European centers, 750 of whom received TRT at at least one visit during the period of observation. Patients on TRT reported rapid and sustained improvements in QOL, with fewer sexual, psychological, and somatic symptoms. Modest improvements in QOL and sexual function, including erectile function, also were noted in RHYME patients not on TRT, although treated patients showed consistently greater benefit over time in all symptom domains compared with untreated patients. AMS total scores for patients on TRT were 32.8 (95% confidence interval = 31.3-34.4) compared with 36.6 (95% confidence interval = 34.8-38.5) for untreated patients (P < .001). Small but significant improvements in IIEF scores over time also were noted with TRT. Approximately 25% of treated and untreated men also used phosphodiesterase type 5 inhibitors, with notable differences in the frequency of phosphodiesterase type 5 inhibitor prescription use according to physician specialty and geographic site location. CLINICAL IMPLICATIONS: TRT-related benefits in QOL and sexual function are well maintained for up to 36 months after initiation of treatment. STRENGTHS AND LIMITATIONS: The major strengths are the large, diverse patient population being treated in multidisciplinary clinical settings. The major limitation is the frequency of switching from one formulation to another. CONCLUSION: Overall, we confirmed the broad and sustained benefits of TRT across major QOL dimensions, including sexual, somatic, and psychological health, which were sustained over 36 months in our treatment cohort. Rosen RC, Wu F, Behre H, et al. Quality of Life and Sexual Function Benefits Effects of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME). J Sex Med 2017;14:1104-1115.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG.

Fortacin™ Spray for the Treatment of Premature Ejaculation.

Premature ejaculation (PE) is a common complaint of male sexual dysfunction affecting men and their partners and consequently causing significant personal and interpersonal distress. Increased sensitivity of the glans penis and abnormalities of the afferent-efferent reflex pathway within the ejaculatory process are involved in the occurrence of PE. Drugs that either selectively reduce penile sensitization or modify the afferent-efferent reflex are well established therapeutic options for PE. Fortacin™ is the first topical treatment to be officially approved for the treatment of primary PE in adult men, and is mentioned as an experimental aerosol (as TEMPE) in the current European Association of Urology guidelines. It was approved for use in the European Union and launched in the United Kingdom in November 2016. Fortacin™ is a eutectic-like mixture of lidocaine 150 mg/mL and prilocaine 50 mg/mL that meets the requirements of an ideal treatment for PE because it is fast acting (within 5 minutes), has durable effects, can be easily used "on-demand", and shows minimal side-effects. The metered-dose spray delivery system allows the desensitizing agents to be deposited in a dose-controlled, concentrated film onto the glans penis consequently reducing its sensitivity. This is translated into a delaying of the ejaculatory latency time without adversely affecting the sensation of ejaculation and orgasmic pleasure. The efficacy and safety of Fortacin™ have been proven by means of increased ejaculatory latency, control, and sexual satisfaction in large scale studies demonstrating the significant benefits for both patients and their partners.

Latest Evidence on the Use of Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

CONTEXT: Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE). OBJECTIVE: Update of the latest evidence on the mechanisms of action, evaluate the current meta-analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE. EVIDENCE ACQUISITION: Literature analysis of basic researches on PDE5-Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5mg. EVIDENCE SYNTHESIS: Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35-4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25-5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01-1.43). Pooled data analyses revealed that tadalafil 5mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement. CONCLUSIONS: PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking. PATIENT SUMMARY: We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction.

Tadalafil 5 mg once daily for the treatment of erectile dysfunction during a 6-month observational study (EDATE): impact of patient characteristics and comorbidities.

BACKGROUND: To explore the impact of patient-characteristics and relevant comorbidities on treatment continuation rates, effectiveness, and satisfaction in patients with erectile dysfunction (ED) who started or switched to tadalafil 5 mg once daily (TAD-OaD) at baseline. METHODS: In the EDATE observational study, phosphodiesterase-type-5 (PDE5)-inhibitor pretreated or naïve ED patients who started or switched to TAD-OaD were prospectively followed for 6 months. Time to discontinuation of TAD-OaD was estimated using the Kaplan-Meier product-limit method at Months 2, 4, and 6 in subgroups stratified by age (18 - 65 years and >65 years), PDE5-inhibitor pretreatment, ED-severity (mild, moderate, severe), and presence or absence of relevant comorbidities (BPH, diabetes, CVD, hypertension, dyslipidemia). LSmean change from baseline in International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores and associated 95 % CIs were assessed using a mixed-model for repeated measures. Visit, ED etiology, and subgroups were included as fixed-effects. RESULTS: Overall, 778 patients received prescriptions for initiating or switching to TAD-OaD at baseline. At Month 2, >90 % of patients remained on TAD-OaD, except those aged >65 years (86.7 %) and patients with severe ED (89.0 %). More than 80 % of patients in all subgroups, except those aged >65 years (75.0 %), continued TAD-OaD at Month 6. There was a significant LSmean negative effect on IIEF- EF domain-score improvement for BPH (LSmean effect [95 % CI]: -2.77 [-4.98, -0.55], p = 0.014), previous PDE5-inhibitor treatment (-2.13 [-3.33,-0.94], p < 0.001), and mild vs moderate ED (-2.00 [-3.54,-0.46], p = 0.011); the latter possibly linked with a bigger treatment-effect in those with more severe ED at baseline. The LSmean effect on change in IIEF-EF was significantly positive for diabetes (2.28 [0.64,3.92], p = 0.007), most likely because those with diabetes had more severe ED at baseline. For all other parameters, no statistically significant LSmean effects in IIEF-EF changes were observed. No comorbidity or baseline-characteristic except age (18 - 65 years vs >65 years: 11.25 [2.96,19.54], p = 0.008) affected changes in EDITS. CONCLUSIONS: Under routine clinical conditions, treatment continuation rate or satisfaction does not seem to be significantly affected by the presence of comorbidities in men who choose ED-treatment with TAD-OaD. The magnitude of treatment effectiveness was affected by certain baseline characteristics and comorbid conditions. TRIAL REGISTRATION: The study (H6D-EW-LVIU) is registered in the German VfA Registry of Non-Interventional Studies (Verband Forschender Arzneimittelhersteller) since 06 December 2011; available at: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_741 .

Oxford School of Sexual Medicine: how are we doing?

INTRODUCTION: Since 2007, the European Society of Sexual Medicine has held an annual 2-week educational residential program at Oxford. The Oxford School of Sexual Medicine provides knowledge and skills learning opportunities for healthcare professionals. AIM: The aim of the current study was to evaluate the impact of Oxford School courses on the daily practice and medical careers of fellows from different countries. METHODS: All participants in the Oxford School programs were invited to anonymously complete a self-administered questionnaire. MAIN OUTCOME MEASURES: The questionnaire comprised three sections: socio-demographic characteristics of the respondents; four Likert-scale score items inquiring about professional background; and 17 closed and two open questions to evaluate the impact of Oxford School on the respondents' practices. Differences in proportions of categorical variables between respondent subgroups were assessed using Pearson χ(2) test. RESULTS: The mean age of the 54 fellows who participated in the study was 44 years (range 28-63 years), 71% were men and 29% were women. Fifty (92%) were physicians, two (4%) psychologists, and two (4%) were sex therapists. Following participation in the Oxford School course, significantly more participants reported spending 50% or more of their clinical time practicing sexual medicine than prior to the course (59% [32] vs. 27% [15], P < 0.001, Figure 1); and significantly more reported spending 50% or more of their working time in clinical research (54% [29] vs. 33% [18], P < 0.001, Figure 2). Forty-six fellows (85%) reported current participation in teaching activities, compared with only 29 (54%) prior to participating in the Oxford School course. CONCLUSION: Educational activities in sexual medicine, such as the Oxford School, may contribute to the advancement of clinical practice, teaching activities, and clinical research of healthcare providers who are interested in sexual medicine.

Female partner's perception of premature ejaculation and its impact on relationship breakups, relationship quality, and sexual satisfaction.

INTRODUCTION: Women's perceptions of the men's ejaculatory behavior, as well as the impact premature ejaculation (PE) has on the couple's functioning, are important factors that need to be considered. AIM: This survey investigated women's perception and importance of ejaculatory function, as well as the specific aspects of PE that cause distress. In addition, the survey further identified the factors with a greater impact on intimacy, relationship, and sexual behavior. METHODS: The 1,463 females belonging to a web panel from three different countries (Mexico, Italy, and South Korea), aged 20-50 years, participated in the survey. A combination of validated and self-constructed questionnaires to assess women's perception of PE, relationship satisfaction and quality, and sexual functioning and satisfaction were used. MAIN OUTCOME MEASURES: Descriptive statistics in form of proportions and percentages, correlation, and regression analyses. RESULTS: A significant correlation between the importance of ejaculatory control and felt distress could be observed (rho = 0.55, P < 0.001). Women reporting less sexual problems considered ejaculatory control more important and reported more PE-related distress (rho = 0.23 and 0.11, respectively; P < 0.001 for both). The male's lack of attention and focus on performance was the most frequently reported reasons for sexual distress (47.6%) followed by "the short time between penetration and ejaculation" (39.9%), and "the lack of ejaculatory control" (24.1%). Almost a quarter of women reported that the man's ejaculatory problem had previously led to relationship breakups (22.8%). Women considering duration to be important were more likely to report breakups. CONCLUSIONS: The study highlights the detrimental effects of PE on relationship and sexual satisfaction in the female partner and how it can lead to the termination of the relationship. Most notably, this is the first study to report that an important source of female distress are not only parameters related to performance such as control or duration but rather inappropriate attention focus and the negligence of other forms of sexual activities.

Physicians' attitude toward female genital plastic surgery: a multinational survey.

INTRODUCTION: The demand for female genital plastic surgery (FGPS) has increased over the last few decades. Yet, to date, there are no objective explicit measurements to define "abnormal" appearance of genital organs. Using the results of this study, we aimed to produce a statement of the European Society for Sexual Medicine (ESSM) on FGPS practice. AIMS: To evaluate the prevalence of demand for FGPS and to explore the attitudes of sexual medicine specialists toward indications for FGPS. METHODS: Attendees of the 2012 Annual Congress of the ESSM in Amsterdam, the Netherlands, were asked to participate in a survey during the congress. MAIN OUTCOME MEASURE: A 25-item self-report, closed-question questionnaire subdivided into three sections: sociodemographic data, professional background, and personal attitudes toward FGPS. RESULTS: Overall, a total of 360 physicians (mean age 48 years; range 23-72) from different medical disciplines completed the survey. There were diverse responses among participants regarding the definition of abnormal labial appearance and the techniques for labial reduction they perform. Overall, 65% responded that FGPS is frequently or occasionally demanded by the patients they treat. Likewise, most physicians (63%) reported that they never perform FGPS. Conversely, only 14% reported that they either frequently or occasionally perform FGPS. Almost one-third of participants believe that FGPS (labial surgery) improves sexual function. Fifty-two percent of participants answered that they believe that self image is the main reason for women to ask for labial surgery. CONCLUSIONS: Self-image was regarded as the main factor in the demand for FGPS. Many practitioners in the field of sexual medicine recommend that women be referred for consultation with a psychiatrist or psychologist before undergoing FGPS.

A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review.

CONTEXT: Androgen modulation of erectile function (EF) is widely accepted. However, the use of testosterone replacement therapy (TRT) in men with erectile dysfunction (ED) has generated an unprecedented debate. OBJECTIVE: To summarize the relevant data on the incidence, diagnosis, and management of ED coexisting with hypogonadism and to develop a pathophysiology-based treatment algorithm. EVIDENCE ACQUISITION: We reviewed the relevant medical literature, with a particular emphasis on original molecular studies, prospective observational data, and randomized controlled trials performed in the past 20 yr. EVIDENCE SYNTHESIS: Testosterone modulates nearly every component involved in EF, from pelvic ganglions to smooth muscle and the endothelial cells of the corpora cavernosa. It also regulates the timing of the erectile process as a function of sexual desire, coordinating penile erection with sex. Epidemiologic studies confirm the significant overlap of hypogonadism and ED; however, most guidelines do not consider the differential diagnosis of hypogonadism or the relevance of subclinical disease. Various clinical tools can help the physician to assess and restore androgen levels in men with ED. Special attention is given to fertility-sparing treatments, due to the increasing number of older men desiring fatherhood. The simultaneous use of phosphodiesterase type 5 inhibitors (PDE5-Is) and TRT has recently been questioned. Originally proposed as a salvage therapy for nonresponders to PDE5-Is, this approach has been inappropriately transformed into a combination therapy. Clinical data are consistent when reinterpreted in the proper framework, whereas molecular evidence remains controversial. CONCLUSIONS: A body of molecular and clinical evidence supports the use of TRT in hypogonadal patients with ED, although the benefit-risk ratio is uncertain in advanced age. Critical appraisal of this evidence enabled the development of a pathophysiology-oriented algorithm designed to avoid inappropriate treatments and support whether to start with TRT, PDE5-I only, or both. Apparently divergent findings are reconciled when TRT is correctly indicated. An improved diagnosis and individualized management is desirable in light of the many available options.