New and Emerging Pharmacological Treatments for PE

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.

• Topical anesthetic creams and sprays are alternative options.
• Lifestyle modifications, like reducing stress, are helpful adjuncts.
• Natural pills should be scrutinized for scientific validation.
• Contraceptive pills do not treat PE but are often confused with treatments.
• Medications may have different durations of action depending on formulation.

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.

• Pills may work by desensitizing penile nerves temporarily.
• Certain antidepressants are used off-label for PE.
• Not all pills are suitable for every age or health condition.
• Effectiveness varies among individuals; patience is necessary.
• Some formulations combine multiple ingredients for synergy.

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. Premature ejaculation (PE), one of the most common male sexual disorders, profoundly affects the quality of life for both the patient and their partner [1].

Topical anesthetic agents

1. Zinc

Many of the proposed definitions for PE lack a foundation in scientific data and lack diagnostic criteria [2, 3]. The International Society for Sexual Medicine (ISSM) defines PE (lifelong and acquired) as characterized by the following criteria: ejaculation which almost always or always occurs prior to or within 1 min of vaginal penetration (lifelong PE) or a clinically significant and upsetting reduction in ejaculation latency time, of often up to 3 min (acquired PE); inability to delay ejaculation in nearly all or all vaginal penetrations (lifelong and acquired PE); and negative personal consequences, such as inconvenience, distress, frustration, and/or avoidance of sexual intimacy (lifelong and acquired PE) [4]. Nevertheless, this widely accepted definition by the ISSM is applicable to heterosexual penis-vagina sexual activities, while we have limited information on how to define PE in other sexual activities, such as anal sex or in men with homosexual orientations.

Epidemiological studies, based on non-validated PE definitions and patient self-reported outcome (PRO) measures, found prevalence of PE complaints in the male population as high as 20–30% [5,6,7,8,9].

• Some pills are available online but may lack quality control.
• Use of medication should be part of a comprehensive treatment plan.
• Understanding the cause of PE helps tailor the best pill choice.
• Long-term use requires medical guidance to avoid dependency.
• Combining pills with sexual therapy can boost confidence.

However, subsequent epidemiology studies applying evidence-based PE definitions found much lower prevalence rates (~5%) for both lifelong and acquired PE [10,11,12,13]. Of note, since PE is frequently a self-reported and self-rated complaint, it is difficult to determine its epidemiology. Complicating the matter further is the fact that PE is diagnosed in some couples pills to get her in the mood instantly based on distress and not on objective symptoms [14]. While the exact etiology of PE remains undetermined [15,16,17,18], the most widely accepted theories regarding the etiology of lifelong PE center on disruptions in neurotransmitter activities within the central nervous system. This includes serotonin, noradrenaline, oxytocin, nitric oxide (NO), and Gama aminobutyric acid (GABA) [19]. Additionally, increased sensitivity of the glans penis [20], erectile dysfunction (ED) [21, 22], genetic polymorphisms [23,24,25,26], hormonal imbalances [27, 28], and prostatic diseases [29, 30] also contribute to its pathophysiology. Further research is necessary to evaluate the impact of these factors on ejaculation physiology. The etiology of acquired PE is more closely associated with underlying medical, psychological, and interpersonal causes, as described by Serefoglu et al. Since the 1990s, the prevailing treatment options for both lifelong and acquired PE have been on-demand topical anesthetics and off-label daily or on-demand selective serotonin reuptake inhibitors (SSRIs) [32], including Dapoxetine, a swiftly absorbed and short-acting SSRI, which stands as the sole approved oral medication for PE treatment. Notably, Dapoxetine lacks approval from the US Food and Drug Administration due to its uncertain efficacy and safety [32]. While the majority of men with PE report these treatments as safe, some may experience minor adverse effects. Additionally, SSRIs offer only a temporary delay in ejaculation latency time, with PE often resurfacing after treatment cessation [32,33,34,35,36]. Certain PE patients and their partners might find the necessity to apply a topical anesthetic 5–10 min before each sexual encounter dissatisfying [37]. A post-marketing study reveals that a significant majority (up to 75%) of PE patients express dissatisfaction with topical anesthetic treatments. Consequently, adherence to topical anesthetic treatments remains low, at ~10% [38]. Behavioral therapy, specifically sex therapy, represents a treatment with fewer side effects and lower costs. Its goal is to enhance self-confidence and alleviate anxiety and depression by systematically training men to acquire sexual skills that can extend ejaculation time. In the short term, behavioral therapy can yield success rates ranging from 45% to 65% of sex tablet for women patients, but its long-term effects remain uncertain [39]. A definitive cure for PE is still elusive, and ongoing research is focused on identifying the optimal treatment for this condition.

Topical Numbing Agents and Non-Pharmacological Treatments

The 12-week PFM rehabilitation program included physio-kinesiotherapy, trans anal probe electrostimulation, and three weekly biofeedback sessions, each lasting 20 min. Of the 122 participants completing PFM rehabilitation, 111 gained control over their ejaculation reflex, resulting in a mean IELT of 161.6 s and a PEDT score of 2.3 at the intervention endpoint, indicating a significant increase from baseline IELT of 40.4 s and PEDT score of 17.0 (P < 0.0001). At the 36-month follow-up, 64% and 56% of the remaining 95 participants maintained satisfactory ejaculation control at 24- and 36-months post-intervention, respectively. Protocols utilizing PFM rehabilitation, incorporating physio-kinesiotherapy, trans-anal probe electrostimulation, and biofeedback, are characterized as protracted and cumbersome, lacking on-demand suitability during intercourse. Patients often necessitate substantial time to comprehend the intricacies of the protocol, essential for achieving control tadalis 20 over their ejaculatory reflex and subsequently applying this knowledge during sexual activity.

Transcutaneous posterior tibial nerve stimulation (TPTNS)

[43] proposed an alternative approach to PE treatment, utilizing transcutaneous electrical neuro stimulation (TENS) on the perineal region. The rationale was that TENS would suppress rhythmic contractions in the expulsion phase by generating a plateau action potential, through continuous stimulation of the bulbospongiosus and ischiocavernosus muscles. Anticipated benefits included hindering muscle relaxation, sustaining the muscles in a sub-tetanic contraction state, thus potentially leading to delayed ejaculation during sexual intercourse. [44] piloted a study to test this hypothesis, employing a commercial TENS device on the perineum of 23 patients with lifelong PE, with each patient serving as their own control. The study compared Masturbating Ejaculatory Latency Time (MELT) with and without TENS during self-sexual stimulation. Consequently, in response to the unmet need for PE therapy, new technologies are currently under development.

Premature ejaculation treatments: pills, wipes, and sprays

Epidemiological studies, based on non-validated PE definitions and patient self-reported outcome (PRO) measures, found prevalence of PE complaints in the male population as high as 20–30% [5,6,7,8,9]. However, subsequent epidemiology studies applying evidence-based PE definitions found much lower prevalence rates (~5%) for both lifelong and acquired PE [10,11,12,13]. Of note, since PE is frequently a self-reported and self-rated complaint, it is difficult to determine its epidemiology. Complicating the matter further is the fact that PE is diagnosed in some couples pills to get her in the mood instantly based on distress and not on objective symptoms [14]. While the exact etiology of PE remains undetermined [15,16,17,18], the most widely accepted theories regarding the etiology of lifelong PE center on disruptions in neurotransmitter activities within the central nervous system.

When should I see a doctor about premature ejaculation?

This includes serotonin, noradrenaline, oxytocin, nitric oxide (NO), and Gama aminobutyric acid (GABA) [19]. Additionally, increased sensitivity of the glans penis [20], erectile dysfunction (ED) [21, 22], genetic polymorphisms [23,24,25,26], hormonal imbalances [27, 28], and prostatic diseases [29, 30] also contribute to its pathophysiology. Further research is necessary to evaluate the impact of these factors on ejaculation physiology. The etiology of acquired PE is more closely associated with underlying medical, psychological, and interpersonal causes, as described by Serefoglu et al. Since the 1990s, the prevailing treatment options for both lifelong and acquired PE have been on-demand topical anesthetics and off-label daily or on-demand selective serotonin reuptake inhibitors (SSRIs) [32], including Dapoxetine, a swiftly absorbed and short-acting SSRI, which stands as the sole approved oral medication for PE treatment. This review article is aimed at providing a summary of the presently available non-pharmacological, non-surgical technological therapies for PE, excluding cognitive or behavioral approaches. We will discuss the findings from studies that are dedicated to creating innovative technological treatment options for PE. Pelvic floor muscles (PFMs), specifically the ischiocavernosus and bulbospongiosus muscles, assume a pivotal role in the expulsion phase of ejaculation, expressed by increase in electromyographic activity during ejaculation [40]. The objective of physio-kinesiotherapy and electrostimulation is to augment the contractile strength of the perineal muscles, complemented by biofeedback to facilitate patients in mastering the recognition and contraction of PFMs, thereby strengthening the urethral sphincter.

Warning: Watch out for unreliable pills

Notably, Dapoxetine lacks approval from the US Food and Drug Administration due to its uncertain efficacy and safety [32]. While the majority of men with PE report these treatments as safe, some may experience minor adverse effects. Additionally, SSRIs offer only a temporary delay in ejaculation latency time, with PE often resurfacing after treatment cessation [32,33,34,35,36]. Certain PE patients and their partners might find the necessity to apply a topical anesthetic 5–10 min before each sexual encounter dissatisfying [37]. A post-marketing study reveals that a significant majority (up to 75%) of PE patients express dissatisfaction with topical anesthetic treatments.

How long does it take for these medications to work?

Consequently, adherence to topical anesthetic treatments remains low, at ~10% [38]. Behavioral therapy, specifically sex therapy, represents a treatment with fewer side effects and lower costs. Its goal is to enhance self-confidence and alleviate anxiety and depression by systematically training men to acquire sexual skills that can extend ejaculation time. In the short term, behavioral therapy can yield success rates ranging from 45% to 65% of sex tablet for women patients, but its long-term effects remain uncertain [39]. A definitive cure for PE is still elusive, and ongoing research is focused on identifying the optimal treatment for this condition. However, a comprehensive understanding of the intricate protocol dynamics is often necessitated, requiring patients to undergo several months of PFM training to gain control over the ejaculatory reflex and adeptly apply acquired skills during sexual activity [40].

• Herbal pills often boast fewer side effects than pharmaceuticals.
• Supplements marketed for delay are often unregulated.
• Proper diagnosis ensures the right treatment approach.
• Pills should not be used as the sole solution; therapy is beneficial.
• Consistency in medication can improve long-term control.

[41], 40 patients with lifelong PE and intravaginal ejaculatory latency time (IELT) values below 1 min underwent a 12-week PFM rehabilitation regimen, comprising physio-kinesiotherapy, trans anal probe electro-stimulation, and thrice-weekly biofeedback sessions. Post-intervention, the mean IELT demonstrated a significant increase compared to baseline values (31.7 s vs.

Further information

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.

Male pelvic floor muscles

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. Premature ejaculation (PE), one of the most common male sexual disorders, profoundly affects the quality of life for both the patient and their partner [1]. Many of the proposed definitions for PE lack a foundation in scientific data and lack diagnostic criteria [2, 3]. The International Society for Sexual Medicine (ISSM) defines PE (lifelong and acquired) as characterized by the following criteria: ejaculation which almost always or always occurs prior to or within 1 min of vaginal penetration (lifelong PE) or a clinically significant and upsetting reduction in ejaculation latency time, of often up to 3 min (acquired PE); inability to delay ejaculation in nearly all or all vaginal penetrations (lifelong and acquired PE); and negative personal consequences, such as inconvenience, distress, frustration, and/or avoidance of sexual intimacy (lifelong and acquired PE) [4]. Nevertheless, this widely accepted definition by the ISSM is applicable to heterosexual penis-vagina sexual activities, while we have limited information on how to define PE in other sexual activities, such as anal sex or in men with homosexual orientations. 146.2 s, respectively, P < 0.0001). [42] retrospectively reviewed 154 participants with baseline IELT values of 60 s or less and Premature Ejaculation Diagnostic Tool (PEDT) scores exceeding 11.

The 12-week PFM rehabilitation program included physio-kinesiotherapy, trans anal probe electrostimulation, and three weekly biofeedback sessions, each lasting 20 min.

Affordable, comprehensive men’s sexual health care you can trust.

Consequently, in response to the unmet need for PE therapy, new technologies are currently under development. This review article is aimed at providing a summary of the presently available non-pharmacological, non-surgical technological therapies for PE, excluding cognitive or behavioral approaches. We will discuss the findings from studies that are dedicated to creating innovative technological treatment options for PE. Pelvic floor muscles (PFMs), specifically the ischiocavernosus and bulbospongiosus muscles, assume a pivotal role in the expulsion phase of ejaculation, expressed by increase in electromyographic activity during ejaculation [40]. The objective of physio-kinesiotherapy and electrostimulation is to augment the contractile strength of the perineal muscles, complemented by biofeedback to facilitate patients in mastering the recognition and contraction of PFMs, thereby strengthening the urethral sphincter.

SSRIs for Premature Ejaculation

However, a comprehensive understanding of the intricate protocol dynamics is often necessitated, requiring patients to undergo several months of PFM training to gain control over the ejaculatory reflex and adeptly apply acquired skills during sexual activity [40]. [41], 40 patients with lifelong PE and intravaginal ejaculatory latency time (IELT) values below 1 min underwent a 12-week PFM rehabilitation regimen, comprising physio-kinesiotherapy, trans anal probe electro-stimulation, and thrice-weekly biofeedback sessions. Post-intervention, the mean IELT demonstrated a significant increase compared to baseline values (31.7 s vs. 146.2 s, respectively, P < 0.0001). [42] retrospectively reviewed 154 participants with baseline IELT values of 60 s or less and Premature Ejaculation Diagnostic Tool (PEDT) scores exceeding 11. Of the 122 participants completing PFM rehabilitation, 111 gained control over their ejaculation reflex, resulting in a mean IELT of 161.6 s and a PEDT score of 2.3 at the intervention endpoint, indicating a significant increase from baseline IELT of 40.4 s and PEDT score of 17.0 (P < 0.0001). At the 36-month follow-up, 64% and 56% of the remaining 95 participants maintained satisfactory ejaculation control at 24- and 36-months post-intervention, respectively. Protocols utilizing PFM rehabilitation, incorporating physio-kinesiotherapy, trans-anal probe electrostimulation, and biofeedback, are characterized as protracted and cumbersome, lacking on-demand suitability during intercourse. Patients often necessitate substantial time to comprehend the intricacies of the protocol, essential for achieving control tadalis 20 over their ejaculatory reflex and subsequently applying this knowledge during sexual activity. [43] proposed an alternative approach to PE treatment, utilizing transcutaneous electrical neuro stimulation (TENS) on the perineal region. The rationale was that TENS would suppress rhythmic contractions in the expulsion phase by generating a plateau action potential, through continuous stimulation of the bulbospongiosus and ischiocavernosus muscles.

Why Choose RedBox Rx

Results indicated significantly higher mean MELT values during TENS treatment compared to self-stimulation without TENS (311.4 s vs. 124.6 s, P = 0.0009), signifying an ~4-fold increase in MELT. Notably, the absence of an established MELT threshold in the literature prompted the researchers to assume a correlation with IELT in PE patients, an assumption lacking scientific validation and constituting a significant study limitation. No patients reported erectile difficulties or severe adverse effects, although a minority experienced minor adverse effects such as discomfort during stimulation and dysuria. This study presents a novel approach to addressing lifelong PE through the extension of on-demand coital duration, achieved via electric stimulation of the ejaculation muscles using the In2 patch.

How does Premature Ejaculation Occur?

This method holds promise as a potential on-demand, non-invasive, and drug-free treatment for PE. However, it is important to note that the study’s scope was constrained by a limited number of participants, the exclusion of those with acquired PE, short-term follow-up, exclusive focus on vaginal penetration, omission of men engaged in anal penetration, exclusion of couples with shorter-term relations, and the use of a device based on a theoretical mechanism of action. Anticipated benefits included hindering muscle relaxation, sustaining the muscles in a sub-tetanic contraction state, thus potentially leading to delayed ejaculation during sexual intercourse. [44] piloted a study to test this hypothesis, employing a commercial TENS device on the perineum of 23 patients with lifelong PE, with each patient serving as their own control. The study compared Masturbating Ejaculatory Latency Time (MELT) with and without TENS during self-sexual stimulation. Results indicated significantly higher mean MELT values during TENS treatment compared to self-stimulation without TENS (311.4 s vs. 124.6 s, P = 0.0009), signifying an ~4-fold increase in MELT. Notably, the absence of an established MELT threshold in the literature prompted the researchers to assume a correlation with IELT in PE patients, an assumption lacking scientific validation and constituting a significant study limitation. No patients reported erectile difficulties or severe adverse effects, although a minority experienced minor adverse effects such as discomfort during stimulation and dysuria. This study presents a novel approach to addressing lifelong PE through the extension of on-demand coital duration, achieved via electric stimulation of the ejaculation muscles using the In2 patch. This method holds promise as a potential on-demand, non-invasive, and drug-free treatment for PE. However, it is important to note that the study’s scope was constrained by a limited number of participants, the exclusion of those with acquired PE, short-term follow-up, exclusive focus on vaginal penetration, omission of men engaged in anal penetration, exclusion of couples with shorter-term relations, and the use of a device based on a theoretical mechanism of action.