madman
Super Moderator
A novel on-demand therapy for lifelong premature ejaculation using a miniature transperineal electrical stimulator—the vPatch: an as-treated analysis (2023)
Arik Shechter, MD, Nicola Mondaini, MD, Ege Can Serefoglu, MD, PhD, Tal Gollan, BSc, Frederic Deutsch, Boaz Appel, MD, Ilan Gruenwald, MD
Abstract
Background: While premature ejaculation (PE) is a common and disturbing sexual dysfunction in men, currently 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 bi-center 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 endpoints 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.
Introduction
Premature ejaculation (PE) is a common and disturbing sexual complaint affecting 20% to 30% of sexually active men, according to the type and definition by professional associations.1-4 PE is associated with detrimental psychological, physical, and social effects,5 yet its etiology remains unclear.6,7 Currently, dapoxetine is the only oral compound developed for treating PE.8,9 Although approved by the European Medical Agency, dapoxetine is not approved by the US Food and Drug Administration due to its undetermined efficacy and safety.10-12 This shows the need for an effective and safe solution for PE.
Ejaculation is a complex reflex with 2 phases: emission and expulsion, both involving several pelviperineal anatomic structures.13 Emission is the advancement of semen into the posterior urethra as a result of epithelial secretion and smooth muscle cell contractions around the epididymis and ductus deferens, propelling the sperm into the prostate and proximal urethra. Expulsion is a spinal cord reflex, which causes the ejection of sperm from the posterior urethra to the meatus. During this phase, smooth muscle bundles contract at the level of the bladder neck to prevent backflow of semen into the bladder, and the pelvic floor striated muscles (mainly the bulbospongiosus and ischiocavernosus) rhythmically contract to propel semen distally throughout the bulbar and penile urethra and toward the meatus.14-16 These muscles have a major functional role in forcefully and rhythmically expelling semen from the meatus outward.
Gruenwald et al17 proposed treating PE by transient inhibition of bulbospongiosus muscle contraction by neuromuscular transcutaneous electrical stimulation (TES). TES delivered to the neuromuscular junction may maintain approximately 80% muscle contraction for several minutes before inflicting muscle fatigue, inhibiting rhythmic contractions during the neural ejaculatory stimulus phase that may result in a delayed ejaculatory latency time. In 2020, Shechter et al18 demonstrated that TES significantly increased the ejaculatory latency time of patients with lifelong PE, using a self-stimulation methodology with a standard commercial neuromuscular electrical stimulation device.
This prospective international bi-center trial is the first on the efficacy and safety of a miniature transperineal electrical stimulator—the vPatch (Virility Medical Ltd)— in men with lifelong PE. This randomized sham-controlled trial was double-blind and conducted in a real-life setting, during coitus, and on demand. Objectives were to determine the safety and efficacy of the device in delaying orgasm, as determined by intravaginal ejaculatory latency time (IELT) and patient-reported outcomes.
Device description
The vPatch device is a flexible, skin-adhering, battery-powered device with an electronic module and 2 electrodes (Figure 1). It is adhered to the perineal skin where once activated, it delivers electrical stimulation transcutaneously to the perineal muscles, inducing continuous tonic muscle contraction. Due to its magnitude and proximity to the perineal skin, the bulbocavernosus muscle is probably affected the most Each patch was preconfigured for active or sham mode before packaging, according to patients’ individual parameters as determined during visit 2.
Discussion
The accumulated knowledge of TES effects on human tissue, specifically muscle activation, led us to initiate a series of studies applying TES to pelvic floor muscles and later to use the newly developed vPatch for treating PE. Essentially, when a muscle undergoes continuous stimulation, the series of successive contractions can prevent muscle relaxation and thus maintain a mild contractile tonus. Applying TES to these muscles during coitus may therefore keep them in sustained contraction for several minutes, which may require a higher central or autonomic stimulatory threshold for initiating the natural rhythmic muscle contractions necessary to complete ejaculation.
Pastore et al25 demonstrated that rehabilitation treatments with electrical stimulation delivered to the pelvic floor can treat lifelong PE. Furthermore, TES results obtained in our previous study with a self-stimulation protocol18 revealed that on-demand electrical stimulation can effectively and safely treat patients with lifelong PE, without their having prior training, significantly increasing ejaculatory latency time. Clinically, in patients with PE, this intervention may be expressed by a significant increase in latency time to ejaculation.
To our knowledge, this is the first rigorously designed study to investigate whether TES could improve symptoms in men with lifelong PE. This randomized double-blind clinical trial demonstrated the potential of the vPatch, a miniaturized TES device, to successfully treat symptoms of lifelong PE. Statistically significant differences were found between the active and sham devices on fold changes in (1) geometric and arithmetic mean IELT; (2) PEP questions on perceived control, personal distress, interpersonal difficulty, and satisfaction; and (3) CGIC. The vPatch was feasible and safe, with rare and minimal nonserious side effects and significant beneficial effects in delaying ejaculation.
Our 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. Unfortunately, of the initially randomized patients, 7 could never use the vPatch due to unexpected life circumstances (eg, road accident, partner-related, COVID-19 restrictions), and 1 used the vPatch only 2 times (before his wife had a chronic health problem). Moreover, the 2- fold increase that was established with the vPatch may not be sufficient for patients whose IELT is very short (eg, 15- 30 seconds). Of note, PE treatments currently approved by the European Medicine Agency (ie, dapoxetine and Fortacin [lidocaine and prilocaine]) have similar ejaculation-delaying efficacy, with more significant side effects.26 Nevertheless, the conclusive results establish a basis for further investigations in a larger group of patients through a wider inclusion protocol.
Whether indicated for PE or off-label, selective serotonin reuptake inhibitors have a low rate of acceptance by patients, mainly due to the lack of spontaneity involved and the significant rates of AEs caused by the treatment.9-11 Thus, new treatment modalities, such as on-demand electrical stimulation, may provide much safer, immediate, and significant beneficial effects that meaningfully improve the sexual well-being of couples in which the man suffers from PE.
Conclusion
There are very few options for treating PE, and although this is a new and ongoing investigation, the results are promising. We demonstrated that TES delivered by the vPatch device was well tolerated and resulted in significant benefits in objective and subjective measures of ejaculatory control in men with lifelong PE. This treatment modality offers the potential as an on-demand drug-free modality for treating PE.
Arik Shechter, MD, Nicola Mondaini, MD, Ege Can Serefoglu, MD, PhD, Tal Gollan, BSc, Frederic Deutsch, Boaz Appel, MD, Ilan Gruenwald, MD
Abstract
Background: While premature ejaculation (PE) is a common and disturbing sexual dysfunction in men, currently 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 bi-center 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 endpoints 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.
Introduction
Premature ejaculation (PE) is a common and disturbing sexual complaint affecting 20% to 30% of sexually active men, according to the type and definition by professional associations.1-4 PE is associated with detrimental psychological, physical, and social effects,5 yet its etiology remains unclear.6,7 Currently, dapoxetine is the only oral compound developed for treating PE.8,9 Although approved by the European Medical Agency, dapoxetine is not approved by the US Food and Drug Administration due to its undetermined efficacy and safety.10-12 This shows the need for an effective and safe solution for PE.
Ejaculation is a complex reflex with 2 phases: emission and expulsion, both involving several pelviperineal anatomic structures.13 Emission is the advancement of semen into the posterior urethra as a result of epithelial secretion and smooth muscle cell contractions around the epididymis and ductus deferens, propelling the sperm into the prostate and proximal urethra. Expulsion is a spinal cord reflex, which causes the ejection of sperm from the posterior urethra to the meatus. During this phase, smooth muscle bundles contract at the level of the bladder neck to prevent backflow of semen into the bladder, and the pelvic floor striated muscles (mainly the bulbospongiosus and ischiocavernosus) rhythmically contract to propel semen distally throughout the bulbar and penile urethra and toward the meatus.14-16 These muscles have a major functional role in forcefully and rhythmically expelling semen from the meatus outward.
Gruenwald et al17 proposed treating PE by transient inhibition of bulbospongiosus muscle contraction by neuromuscular transcutaneous electrical stimulation (TES). TES delivered to the neuromuscular junction may maintain approximately 80% muscle contraction for several minutes before inflicting muscle fatigue, inhibiting rhythmic contractions during the neural ejaculatory stimulus phase that may result in a delayed ejaculatory latency time. In 2020, Shechter et al18 demonstrated that TES significantly increased the ejaculatory latency time of patients with lifelong PE, using a self-stimulation methodology with a standard commercial neuromuscular electrical stimulation device.
This prospective international bi-center trial is the first on the efficacy and safety of a miniature transperineal electrical stimulator—the vPatch (Virility Medical Ltd)— in men with lifelong PE. This randomized sham-controlled trial was double-blind and conducted in a real-life setting, during coitus, and on demand. Objectives were to determine the safety and efficacy of the device in delaying orgasm, as determined by intravaginal ejaculatory latency time (IELT) and patient-reported outcomes.
Device description
The vPatch device is a flexible, skin-adhering, battery-powered device with an electronic module and 2 electrodes (Figure 1). It is adhered to the perineal skin where once activated, it delivers electrical stimulation transcutaneously to the perineal muscles, inducing continuous tonic muscle contraction. Due to its magnitude and proximity to the perineal skin, the bulbocavernosus muscle is probably affected the most Each patch was preconfigured for active or sham mode before packaging, according to patients’ individual parameters as determined during visit 2.
Discussion
The accumulated knowledge of TES effects on human tissue, specifically muscle activation, led us to initiate a series of studies applying TES to pelvic floor muscles and later to use the newly developed vPatch for treating PE. Essentially, when a muscle undergoes continuous stimulation, the series of successive contractions can prevent muscle relaxation and thus maintain a mild contractile tonus. Applying TES to these muscles during coitus may therefore keep them in sustained contraction for several minutes, which may require a higher central or autonomic stimulatory threshold for initiating the natural rhythmic muscle contractions necessary to complete ejaculation.
Pastore et al25 demonstrated that rehabilitation treatments with electrical stimulation delivered to the pelvic floor can treat lifelong PE. Furthermore, TES results obtained in our previous study with a self-stimulation protocol18 revealed that on-demand electrical stimulation can effectively and safely treat patients with lifelong PE, without their having prior training, significantly increasing ejaculatory latency time. Clinically, in patients with PE, this intervention may be expressed by a significant increase in latency time to ejaculation.
To our knowledge, this is the first rigorously designed study to investigate whether TES could improve symptoms in men with lifelong PE. This randomized double-blind clinical trial demonstrated the potential of the vPatch, a miniaturized TES device, to successfully treat symptoms of lifelong PE. Statistically significant differences were found between the active and sham devices on fold changes in (1) geometric and arithmetic mean IELT; (2) PEP questions on perceived control, personal distress, interpersonal difficulty, and satisfaction; and (3) CGIC. The vPatch was feasible and safe, with rare and minimal nonserious side effects and significant beneficial effects in delaying ejaculation.
Our 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. Unfortunately, of the initially randomized patients, 7 could never use the vPatch due to unexpected life circumstances (eg, road accident, partner-related, COVID-19 restrictions), and 1 used the vPatch only 2 times (before his wife had a chronic health problem). Moreover, the 2- fold increase that was established with the vPatch may not be sufficient for patients whose IELT is very short (eg, 15- 30 seconds). Of note, PE treatments currently approved by the European Medicine Agency (ie, dapoxetine and Fortacin [lidocaine and prilocaine]) have similar ejaculation-delaying efficacy, with more significant side effects.26 Nevertheless, the conclusive results establish a basis for further investigations in a larger group of patients through a wider inclusion protocol.
Whether indicated for PE or off-label, selective serotonin reuptake inhibitors have a low rate of acceptance by patients, mainly due to the lack of spontaneity involved and the significant rates of AEs caused by the treatment.9-11 Thus, new treatment modalities, such as on-demand electrical stimulation, may provide much safer, immediate, and significant beneficial effects that meaningfully improve the sexual well-being of couples in which the man suffers from PE.
Conclusion
There are very few options for treating PE, and although this is a new and ongoing investigation, the results are promising. We demonstrated that TES delivered by the vPatch device was well tolerated and resulted in significant benefits in objective and subjective measures of ejaculatory control in men with lifelong PE. This treatment modality offers the potential as an on-demand drug-free modality for treating PE.
