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.

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.

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.

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.

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.

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.

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 .

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 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.

New developments in education and training in sexual medicine.

INTRODUCTION.: The past 12 months have been historic ones for the field of Sexual Medicine in that we have seen the creation of the European Board examination in Sexual Medicine with the title of "Fellow of the European Committee on Sexual Medicine" (FECSM) offered to successful candidates. AIM.: The study aims to promote a high standard of care in Sexual Medicine. METHODS.: An important way of promoting high standards of care is by the development of training, regulation, and assessment framework. The background to these developments and the recent educational activities of the European Society for Sexual Medicine (ESSM) are described in this article. RESULTS.: The creation of the Multidisciplinary Joint Committee on Sexual Medicine (MJCSM) under the auspices of the European Union of Medical Specialists, with the primary purpose to develop the highest possible standards of training in Sexual Medicine in Europe, made it possible to create a process for qualification in Sexual Medicine. The ESSM educational activities created opportunities to support trainees in Sexual Medicine and the first MJCSM exam was held in Amsterdam with a high overall success rate. CONCLUSION.: These activities are intended to improve quality. The FECSM examination is the first of its type and provides a real opportunity for Sexual Medicine physicians to demonstrate and document their knowledge.

Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: analyses of pooled data from four randomized, placebo-controlled tadalafil clinical studies.

INTRODUCTION: Erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions. AIM: The study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes. METHODS: Data were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4-week placebo run-in; changes from baseline were assessed vs. placebo using analysis of covariance. MAIN OUTCOME MEASURES: International Prostate Symptom Score (IPSS), IPSS subscores, Quality-of-Life Index (IPSS-QoL), BPH Impact Index (BII), and International Index of Erectile Function-Erectile Function (IIEF-EF) Domain score were used in this study. RESULTS: Tadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were -6.0 and -3.6, respectively (P < 0.001). Improvements in IIEF-EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS-QoL, and BII (all P < 0.001). No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF-EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF-EF Domain score during treatment were weakly correlated (r = -0.229). Treatment-emergent adverse events were consistent with previous reports. CONCLUSIONS: Tadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF-EF Domain score were weakly correlated.

SOP conservative (medical and mechanical) treatment of erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships. AIM: The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures. METHODS: The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included. RESULTS: Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation.

A randomized open-label trial with a crossover comparison of sexual self-confidence and other treatment outcomes following tadalafil once a day vs. tadalafil or sildenafil on-demand in men with erectile dysfunction.

AIM: To compare Sexual Self-Confidence and other treatment outcomes following 8 weeks of treatment with tadalafil 5 mg once a day (OaD) vs. tadalafil 20 mg or sildenafil 100 mg as needed (pro re nata [PRN]) in patients with erectile dysfunction (ED). METHODS: A randomized, open-label, crossover study in men ≥18 years of age with history of ED and satisfactory response to current oral phosphodiesterase 5 (PDE5) inhibitor PRN. Data were analyzed with a mixed effects model for crossover design. MAIN OUTCOME MEASURES: The primary outcome measure was the Sexual Self-Confidence domain of the Psychological and Interpersonal Relationship Scales (PAIRS) between tadalafil OaD and sildenafil PRN. SECONDARY OUTCOMES INCLUDED: Time Concerns and Spontaneity domains of PAIRS, and the Self-Esteem and Relationship (SEAR) scale. RESULTS: Men naive to tadalafil OaD were enrolled (N = 378), with 61-69% prior PDE5 inhibitor use. There were improvements in all PAIRS domains from baseline when comparing tadalafil OaD and PRN with sildenafil PRN (P < 0.001). The Sexual Self-Confidence domain improved from baseline and was 0.50 ± 0.78 following tadalafil OaD, 0.5 ± 0.72 for tadalafil PRN, and 0.39 ± 0.67 for sildenafil PRN. The difference in least-squares mean was 0.12 ± 0.04 (confidence interval [CI] = 0.04, 0.19; P = 0.001) between tadalafil OaD and sildenafil PRN and 0.01 ± 0.04 (CI = -0.06, 0.08; P = 0.872) between tadalafil OaD and tadalafil PRN. The Time Concerns domain score was lower with tadalafil OaD than tadalafil PRN (P < 0.001). There were no differences in SEAR scores between treatments. CONCLUSIONS: Tadalafil OaD and tadalafil PRN compared with sildenafil PRN demonstrated greater improvements in Sexual Self-Confidence, Time Concerns, and Spontaneity. There was no significant difference in Sexual Self-Confidence between tadalafil OaD and tadalafil PRN. Changes in SEAR, the erectile function domain of the International Index of Erectile Function, and the Erectile Dysfunction Inventory of Treatment Satisfaction scores from baseline to end point were similar.

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.

An overview of pharmacotherapy in premature ejaculation.

INTRODUCTION: With increasing interest and clinical research in male sexual disorders, it has become clear that not only psychological but also organic, neurobiological, and genetic factors may play an important role in premature ejaculation (PE). AIM: This article provides an overview of the different treatment options both for lifelong (primary, "congenital") and acquired (secondary) PE. METHODS: Review of the literature. MAIN OUTCOME MEASURES: Currently used treatment options for PE. RESULTS: Treatments reviewed include psychological/behavioral/sexual counseling therapy, topical anesthetics, dapoxetine, and other selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and phosphodiesterase-5 (PDE-5) inhibitors. CONCLUSIONS: Before starting any therapy for PE, correct diagnosis has to be made considering the patient's reported intravaginal ejaculatory latency time (IELT) and the duration and type of PE. Concomitant erectile dysfunction (ED) should be either ruled out or proven by appropriate means. In uncomplicated cases of PE with stable partnerships, medical treatment represents the first-choice option with a high likelihood of success. Dapoxetine, where available, or other SSRIs provide suitable therapeutic options with a good risk/benefit profile for patients. In complicated ("difficult-to-treat") PE patients, a combination of medication and sexual counseling should be considered the first treatment option. Combination therapies of PDE-5 inhibitors and PE-related medications should be offered to patients suffering from comorbid PE and ED, with ED treatment starting first. In those patients with severe PE-IELTs of <30-60 seconds or anteportal ejaculation-combination therapy of topical and oral medications can be offered and may considerably increase IELT, compared with either monotherapy.

Oral agents for the treatment of premature ejaculation: review of efficacy and safety in the context of the recent International Society for Sexual Medicine criteria for lifelong premature ejaculation.

INTRODUCTION: New diagnostic criteria for lifelong premature ejaculation (PE) have been proposed by the International Society of Sexual Medicine (ISSM), including an intravaginal ejaculatory latency time (IELT) of less than about 1 minute, lack of control over ejaculation, and PE-related distress or bother. AIM: The aim of this study was to review evidence supporting the efficacy and safety of oral agents for the treatment of PE in the context of the new ISSM criteria. METHODS: The PubMed database was searched for randomized, double-blind, placebo-controlled studies of oral agents in PE that included stopwatch measurements of IELT. MAIN OUTCOME MEASURES: The main outcome measure used for this study was a review of the efficacy and safety data of oral agents for PE aligned with ISSM criteria. RESULTS: Since the latest meta-analyses using similar criteria (conducted in 2004 and 2005 for selective serotonin reuptake inhibitors [SSRIs] and phosphodiesterase type 5 [PDE-5] inhibitors, respectively), eight studies evaluated SSRIs vs. placebo, one compared SSRIs, two evaluated PDE-5 inhibitors, and one evaluated an SSRI/PDE-5 inhibitor combination. New agents included dapoxetine (five studies) and tramadol (one study). Six studies enrolled men who met an approximation of the ISSM criteria. Although evidence suggests that most SSRIs, tramadol, and dapoxetine increase IELT to varying degrees, few studies included control over ejaculation and PE-related distress or bother as enrollment criteria or used validated patient-reported outcome instruments to evaluate these parameters. Among studies that provided comprehensive adverse event data, safety and tolerability observations in men with PE were generally similar to those observed in other populations; however, with the exception of dapoxetine, known SSRI-class effects (e.g., withdrawal syndrome) were not evaluated in men with PE. CONCLUSIONS: This systematic review of well-controlled clinical trials in PE has demonstrated that while many oral agents, particularly SSRIs, tramadol, and dapoxetine, have proven effective and safe for the treatment of men with PE, few have been evaluated for their effects on the specific elements of the ISSM criteria.

A randomized, double-blind, placebo-controlled, parallel study to assess the efficacy and safety of once-a-day tadalafil in men with erectile dysfunction who are naïve to PDE5 inhibitors.

INTRODUCTION: The majority of subjects included in previous tadalafil once-a-day clinical trials were non-naïve to previous phosphodiesterase 5 (PDE5) inhibitors on demand. A study on PDE5 inhibitor naïve subjects was therefore warranted. AIM: To evaluate the efficacy and safety of once-a-day tadalafil in PDE5 inhibitor-naïve men with erectile dysfunction (ED). MAIN OUTCOMES MEASURES: Primary efficacy end points were changes from baseline to end point in the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score and the per-subject proportion of "yes" responses to sexual encounter profile (SEP) question 2 (SEP2) and question 3 (SEP3). METHODS: PDE5 inhibitor-naïve men with ED (N=217) were randomized in a 1:2 ratio to receive placebo or tadalafil 5 mg once a day for 12 weeks. Enrollment began in January 2009 and the last subject completed in January 2010. RESULTS: At end point, least square mean change from baseline IIEF-EF domain score (7.3 vs. 3.4), SEP2 (23.8% vs. 12.2%) and SEP3 (39.5% vs. 21.5%), was significantly larger for tadalafil vs. placebo (all P<0.001). The most common adverse events (AEs) in tadalafil-treated subjects were back pain, nasopharyngitis, dyspepsia, headache, and myalgia. Four subjects (2.7%) in the tadalafil group and one subject (1.4%) in the placebo group discontinued because of AEs. CONCLUSIONS: In PDE5 inhibitor-naïve men, tadalafil once a day significantly improved EF compared with placebo. Safety results were consistent with previous tadalafil once-a-day clinical trials.

Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).

INTRODUCTION: Addition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels. AIMS: To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant. METHODS: A multicenter, multinational, double-blind, placebo-controlled study of 173 men, 45-80 years, nonresponders to treatment with different PDE5-Is, with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double-blind, placebo-controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory. Main Outcomes Measures. Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question). RESULTS: Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5-Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS: The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5-I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤ 3 ng/mL.

Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials.

INTRODUCTION: Dapoxetine has been evaluated for the on-demand treatment of premature ejaculation (PE) in five phase 3 studies in various populations worldwide and has recently been approved in several countries. AIM: To present integrated efficacy and safety data from phase 3 trials of dapoxetine. METHODS: Data were from five randomized, multicenter, double-blind, placebo-controlled studies conducted in over 25 countries. Men (N=6,081)≥18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE; four studies required a baseline intravaginal ejaculatory latency time (IELT) of ≤2 minutes. Dapoxetine 30 and 60 mg on demand (prn; 1-3 hours before intercourse) were evaluated for either 12 or 24 weeks in four studies; one study evaluated dapoxetine 60 mg daily (qd; included in safety assessments only) or prn for 9 weeks. MAIN OUTCOME MEASURES: End points included stopwatch-measured IELT, Premature Ejaculation Profile (PEP) items, clinical global impression of change (CGIC) in PE, and adverse events (AEs). RESULTS: Average IELT (mean [standard deviation], geometric mean [standard error]) increased from baseline (across groups, 0.9 [0.49] minutes, 0.8 [1.01] minutes) to a significantly greater extent with dapoxetine 30 (3.1 [3.91] minutes, 2.0 [1.03] minutes) and 60 mg (3.6 [3.85] minutes, 2.3 [1.03] minutes) vs. placebo (1.9 [2.43] minutes, 1.3 [1.02] minutes; P<0.001 for all) at week 12 (geometric mean fold increase, 2.5, 3.0, and 1.6, respectively). All PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P<0.001 for all). The most common AEs included nausea, dizziness, and headache, and evaluation of validated instruments demonstrated no anxiety, akathisia, suicidality, or changes in mood with dapoxetine use and no discontinuation syndrome following abrupt withdrawal. CONCLUSIONS: In this diverse population, dapoxetine significantly improved all aspects of PE and was generally well tolerated.