New technologies developed for treatment of premature ejaculation.

Premature ejaculation (PE), lifelong and acquired, is the most common male sexual disorder, with serious impacts on the patient and his partner's quality of life, sexual well-being, and psychosocial health. The most popular treatment options are on-demand topical anesthetics and off-label daily or on-demand selective serotonin reuptake inhibitors (SSRIs), followed by behavioral therapy. While SSRI treatments are reportedly safe, they are associated with limited efficacy and provide only a temporary delay in ejaculation latency time. The majority of PE patients are dissatisfied with SSRIs; thus, adherence to on-demand or daily SSRI treatments is low. In this article, we review studies on currently available technologies that are not pharmacological, surgical, cognitive or behavioral therapies. Recent data from studies of newly developed medical devices used in PE treatment are encouraging as they provide drug-free spontaneity during coitus, without severe adverse effects.

Radiofrequency energy in the treatment of erectile dysfunction-a novel cohort pilot study on safety, applicability, and short-term efficacy.

The erectile mechanism depends, in part on the intactness of the collagen components in the penis. As such, impaired collagen may have a deleterious effect on erectile function. Radiofrequency energy has been shown to renew and restore spatial structural arrangement of collagen fibers; therefore, treatment of erectile dysfunction with radiofrequency could lead to anatomical and physiological changes at the penile tissue level and could lead to improvement in the erectile mechanism. We conducted this study to assess the effect of radiofrequency treatment on erection quality. We evaluated the safety, applicability, and efficacy of a self-applied, handheld, low-intensity radiofrequency device (Vertica®) in men with moderate and mild-to-moderate organic erectile dysfunction. The treatment protocol consisted of 12 treatments (twice a week during the 1st month, and once a week during the 2nd month), and each participant treated himself individually. Treatment outcomes were evaluated using the International Index of Erectile Function, Erection Hardness Scale, Erectile Dysfunction Index of Treatment Satisfaction, Benefit, Satisfaction & Willingness to continue, Quality of Erection Questionnaire, Sexual Quality of Life questionnaires and specific questions addressing side effects and ease of use. Twenty-eight out of 32 men (mean age 59.5 ± 9.8, range: 41-78 years) completed a one-month follow-up after treatment. Mean International Index of Erectile Function (43.7. ± 7.8 vs. 60.9 ± 10.8, p < 0.01), International Index of Erectile Function -Erection Function domain (16.8 ± 3.1 vs. 24.4 ± 4.4, p < 0.001), and Erection Hardness Scores (2.2 ± 0.8 vs. 3.2 ± 0.5, p = 0.01) were all significantly improved. Fifty percent of patients achieved normal erectile function parameters according to the International Index of Erectile Function -Erection Function domain score >25. High mean scores were achieved in the Erectile Dysfunction Index of Treatment Satisfaction (76.8 ± 20.3), Benefit, Satisfaction & Willingness to continue (4.83 ± 1.1), Quality of Erection Questionnaire (73.4 ± 23.8), and Sexual Quality of Life (67 ± 29.4) questionnaires. No side effects were reported and participants rated the device as very comfortable, simple, and easy to operate.

A novel on-demand therapy for lifelong premature ejaculation using a miniature transperineal electrical stimulator-the vPatch: an as-treated analysis.

BACKGROUND: While premature ejaculation (PE) is a common and disturbing sexual dysfunction in men, current available treatment modalities have limited efficacy and low treatment adherence. AIM: To assess the feasibility, safety, and efficacy of the vPatch, a miniaturized on-demand perineal transcutaneous electrical stimulation device for treating PE. METHODS: This prospective bicenter international first-in-human clinical study consisted of 2 arms, was sham controlled, and had a randomized double-blind design. In terms of statistical power calculation, 59 patients aged 21 to 56 years (mean ± SD, 39.8 ± 9.28) with lifelong PE were included. During the initial visit, intravaginal ejaculatory latency time (IELT) was measured over a 2-week run-in period. Eligibility was confirmed in visit 2, based on IELT values, medical and sexual history, and patients' individualized sensory and motor activation thresholds during perineal stimulation with the vPatch. Patients were randomized to the active (vPatch) and sham device groups in a 2:1 ratio, respectively. The vPatch device's safety profile was determined by comparing the incidence of treatment-emergent adverse events. During visit 3, IELTs, Clinical Global Impression of Change scores, and Premature Ejaculation Profile questionnaire outcomes were recorded. Primary end points assessed vPatch device efficacy as mean change in geometric mean IELT; each person was compared with himself, with and without the device, and the sham group was compared with the active group. OUTCOMES: Outcomes included changes in IELT and Premature Ejaculation Profile before and after treatment, last visit Clinical Global Impression of Change scores, and vPatch safety profile. RESULTS: Of 59 patients, 51 completed the study: 34 in the active group and 17 in the sham group. The baseline geometric mean IELT significantly increased from 67 to 123 seconds (P < .01) in the active group, as compared with an insignificant increase from 63 to 81 seconds (P = .17) in the sham group. The increase in mean IELT in the active group was significantly higher than in the sham group (56 vs 18 seconds, P = .01). IELT significantly increased by 3.1 times in the active vs sham group. The mean ratio of fold change (active:sham) was 1.4, significantly different from 1.0 (P = .02). No serious adverse events were reported. CLINICAL IMPLICATIONS: Therapeutic use of the vPatch during coitus may become an on-demand, noninvasive, and drug-free treatment for PE. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first rigorous study investigating whether transcutaneous electrical stimulation during coitus could improve the symptoms of men with lifelong PE. The study is limited by the small number of patients, the exclusion of patients with acquired PE, the short-term follow up, and the use of a device based on a theoretic mechanism of action. CONCLUSION: We demonstrated the possibility to treat lifelong PE by prolonging coitus on demand, using electric stimulation of ejaculation muscles with the vPatch.Clinical trial registration: NCT03942367 (ClinicalTrials.gov).

Peripheral B cells repress B-cell regeneration in aging through a TNF-α/IGFBP-1/IGF-1 immune-endocrine axis.

Loss of B lymphocyte regeneration in the bone marrow (BM) is an immunologic hallmark of advanced age, which impairs the replenishment of peripheral B-cell subsets and results in impaired humoral responses, thereby contributing to immune system dysfunction associated with aging. A better understanding of the mechanism behind this loss may suggest ways to restore immune competence and promote healthy aging. In this study, we uncover an immune-endocrine regulatory circuit that mediates cross-talk between peripheral B cells and progenitors in the BM, to balance B-cell lymphopoiesis in both human and mouse aging. We found that tumor necrosis factor α (TNF-α), which is increasingly produced by peripheral B cells during aging, stimulates the production of insulin-like growth factor-binding protein 1 (IGFBP-1), which binds and sequesters insulin-like growth factor 1 (IGF-1) in the circulation, thereby restraining its activity in promoting B-cell lymphopoiesis in the BM. Upon B-cell depletion in aging humans and mice, circulatory TNF-α decreases, resulting in increased IGF-1 and reactivation of B-cell lymphopoiesis. Perturbation of this circuit by administration of IGF-1 to old mice or anti-TNF-α antibodies to human patients restored B-cell lymphopoiesis in the BM. Thus, we suggest that in both human and mouse aging, peripheral B cells use the TNF-α/IGFBP-1/IGF-1 axis to repress B-cell lymphopoiesis. This trial was registered at www.clinicaltrials.govas#NCT00863187.

Transcutaneous functional electrical stimulation-a novel therapy for premature ejaculation: results of a proof of concept study.

Premature Ejaculation (PE) is a very common and disturbing sexual dysfunction in men. Currently available treatment modalities are associated with limited efficacy and low treatment adherence. In this prospective, single-blinded, self-controlled study, we evaluated the efficacy and safety of transcutaneous electrical stimulation (TES) for the treatment of (PE). We included 23 patients aged 20-60 (mean: 38.7) with lifelong PE. On the first visit, we delivered either TES or sham treatment to the perineum, based on the enrollment order. For stimulation, we used a commercial neuromuscular electrical stimulation device. The patients were invited for the second visit after at least 7 days for receiving the alternating treatment. During the treatment sessions, the patients were left alone in a privet silent room to masturbate and a stopwatch was used to measure their masturbation ejaculatory latency time (MELT). The patients also filled-out safety questionnaires after each visit and on each of the 3 following days. Of the 20 patients who completed the study, 17 (85%) experienced prolonged MELT under TES compared with the sham treatment. Mean MELT values increased 3.5-folds under TES (p = 0.0009). We demonstrated a significant increase in MELT in lifelong PE patients using TES. This therapeutic option may have the potential to become an on-demand treatment option for PE. Future studies with wireless devices are needed to confirm the efficacy and safety of this treatment concept during intercourse.

Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging.

Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B-cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B-cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B-cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B-cell compartments. B-cell depletion in old mice resulted in rejuvenated B-cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"-like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B-cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"-like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B-cell compartment in aging, through B-cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.

Low Intensity Shock Wave Treatment for Erectile Dysfunction-How Long Does the Effect Last?

PURPOSE: We studied the long-term efficacy of penile low intensity shock wave treatment 2 years after an initially successful outcome. MATERIALS AND METHODS: Men with a successful outcome of low intensity shock wave treatment according to the minimal clinically important difference on the IIEF-EF (International Index of Erectile Function-Erectile Function) questionnaire were followed at 6, 12, 18 and 24 months. Efficacy was assessed by the IIEF-EF. Failure during followup was defined as a decrease in the IIEF-EF below the minimal clinically important difference. RESULTS: We screened a total of 156 patients who underwent the same treatment protocol but participated in different clinical studies. At 1 month treatment was successful in 99 patients (63.5%). During followup a gradual decrease in efficacy was observed. The beneficial effect was maintained after 2 years in only 53 of the 99 patients (53.5%) in whom success was initially achieved. Patients with severe erectile dysfunction were prone to earlier failure than those with nonsevere erectile dysfunction. During the 2-year followup the effect of low intensity shock wave treatment was lost in all patients with diabetes who had severe erectile dysfunction at baseline. On the other hand, patients with milder forms of erectile dysfunction without diabetes had a 76% chance that the beneficial effect of low intensity shock wave treatment would be preserved after 2 years. CONCLUSIONS: Low intensity shock wave treatment is effective in the short term but treatment efficacy was maintained after 2 years in only half of the patients. In patients with milder forms of erectile dysfunction the beneficial effect is more likely to be preserved.

Transcutaneous neuromuscular electrical stimulation may be beneficial in the treatment of premature ejaculation.

Approximately 20-30% of sexually active men suffer from Premature Ejaculation (PE), but the pathophysiology still remains unclear and the current available treatments for PE are unsatisfying. Considering the role of rhythmic bulbospongiosus and ischiocavernosus Muscles contractions on the ejaculatory reflex, we hypothesize that weakening this muscles via inhibiting it's contractions by Application of Neuromuscular Electrical Stimulation prior to the planned sexual activity, may have a beneficial effect in the treatment of PE. Using miniaturized perineal on-demand stimulation device, in a home setting during sexual intercourse may become the first line of treatment for PE.

Attitudes of Sexual Medicine Specialists Toward Premature Ejaculation Diagnosis and Therapy.

INTRODUCTION: Premature ejaculation (PE) is one of the commonest sexual dysfunctions in men. Because the definition of and guidelines for the management of PE have been revised in recent years, our understanding of PE has changed. AIM: To investigate the clinical practice patterns of sexual medicine specialists regarding the diagnosis and treatment of PE. METHODS: Attendees of the 17th Annual Congress of the European Society of Sexual Medicine, held in February 2015 in Copenhagen, Denmark, were asked to participate in a survey during the congress. MAIN OUTCOME MEASURES: A 23-item, self-reported, closed-question questionnaire was distributed. Sociodemographic data, professional background, and personal practice patterns of the attendees were assessed in relation to PE. RESULTS: In total, 217 physicians (median age = 47 years, range = 22-74) completed the survey. Most responders (79.3%) considered PE an important sexual dysfunction that should be treated. Almost half the participants stated there is insufficient information about PE for patients and physicians (46.1% and 45.2%, respectively). When asked about the main goal of treating PE, two thirds responded that main goal is to improve patients' sexual function and 35.9% responded that the main goal was to improve partners' satisfaction. CONCLUSION: These findings confirmed that there are many differences among sex health experts in their understanding of PE. Educational activities are crucial in implementing the new guidelines on PE.

Penile Low Intensity Shock Wave Treatment is Able to Shift PDE5i Nonresponders to Responders: A Double-Blind, Sham Controlled Study.

PURPOSE: We performed sham controlled evaluation of penile low intensity shock wave treatment effect in patients unable to achieve sexual intercourse using PDE5i (phosphodiesterase type 5 inhibitor). MATERIALS AND METHODS: This prospective, randomized, double-blind, sham controlled study was done in patients with vasculogenic erectile dysfunction who stopped using PDE5i due to no efficacy. All patients had an erection hardness score of 2 or less with PDE5i. A total of 58 patients were randomized, including 37 treated with low intensity shock waves (12 sessions of 1,500 pulses of 0.09 mJ/mm(2) at 120 shock waves per minute) and 18 treated with a sham probe. In the sham group 16 patients underwent low intensity shock wave treatment 1 month after sham treatment. All patients were evaluated at baseline and 1 month after the end of treatment using validated erectile dysfunction questionnaires and the flow mediated dilatation technique for penile endothelial function. Erectile function was evaluated while patients were receiving PDE5i. RESULTS: In the low intensity shock wave treatment group and the sham group 54.1% and 0% of patients, respectively, achieved erection hard enough for vaginal penetration, that is an EHS (Erection Hardness Score) of 3 (p <0.0001). According to changes in the IIEF-EF (International Index of Erectile Function-Erectile Function) score treatment was effective in 40.5% of men who received low intensity shock wave treatment but in none in the sham group (p = 0.001). Of patients treated with shock waves after sham treatment 56.3% achieved erection hard enough for penetration (p <0.005). CONCLUSIONS: Low intensity shock wave treatment is effective even in patients with severe erectile dysfunction who are PDE5i nonresponders. After treatment about half of them were able to achieve erection hard enough for penetration with PDE5i. Longer followup is needed to establish the place of low intensity shock wave treatment in these challenging cases.

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.

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.

Sexual Health and Overall Wellness (SHOW) survey in men and women in selected European and Middle Eastern countries.

OBJECTIVE: To investigate whether better sexual health is associated with improvements in overall health and wellness, a more loving and intimate relationship, and a more positive outlook on life. METHODS: The Sexual Health and Overall Wellness survey used self-administered questionnaires to collect data from men and women aged 25-74 years who had had sexual intercourse at least once within the previous 12 months. RESULTS: Across nine countries, 3780 self-administered questionnaires were completed: 1893 from men (mean age, 44.6 years); 1887 from women (mean age, 44.2 years). The majority of men and women were satisfied with the frequency of sexual intercourse over the previous 4 weeks (59% and 66%, respectively); the majority (67% and 55%, respectively) reported that having sex was 'very important' or 'absolutely essential'. For men and women, there was a strong association between satisfaction with sex and overall health, and between satisfaction with sex and an overall positive outlook on life. CONCLUSION: For men and women, satisfaction with different aspects of sex was important, and was strongly associated with satisfaction with general health, relationships and other aspects of wellbeing.

[The Objective Structured Clinical Examination and its potential applications as an assessment and feedback tool for IDF primary care physicians--a pilot study].

BACKGROUND: In recent years, the Israel Defense Forces IDF developed special training programs for junior military physicians at the beginning of their service and CME courses for senior military physicians. The Objective Structured Clinical Examination (OSCE) is a well established assessment tool in medical education that can be of vast use in military training programs for primary care physicians. AIM: To evaluate the OSCE as an assessment tool of military primary care physicians. METHODS: Forty-one military primary care physicians completed a 10-station OSCE. The clinical scenario choices were based on the most prevalent problems in the annual statistics of the Israeli Medical Corps between the years 1988-1998. Each station consisted of two parts: a doctor-SP (standardized patient) encounter and a written exercise. Both parts were evaluated by checklists designed and validated by a committee of OSCE experts and senior military physicians. RESULTS: The overall reliability of the exam was alpha = .88. The examinees highly valued the relevance of the scenarios to their every day practice (4.38 out of 5.0) and the reliability of the standardized patients (4.0 out of 5.0). A total of 92% request feedback on their performance. CONCLUSIONS: This pilot study found the OSCE to be a feasible, valid and reliable tool that can serve to assess the capability of physicians to deal with major issues in military primary health care. The OSCE can also play a major role in structured feedback provided to these physicians.