Free standard shipping or expedited/overnight available. To analyse the current therapeutic options for patients with premature ejaculation (PE) and highlight their mechanism(s) of action, effectiveness, advantages and limitations.
Free standard shipping or expedited/overnight available. To analyse the current therapeutic options for patients with premature ejaculation (PE) and highlight their mechanism(s) of action, effectiveness, advantages and limitations. A literature search was conducted using the PubMed database searching for articles exploring different PE treatment modalities. A Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) approach was used to report the results of the literature search. A total of 149 articles were included in this review.
The currently available treatment methods for PE include behavioural therapy, local anaesthetics, tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective phosphodiesterase inhibitors. Most PE treatments are either experimental or used off-label. New treatments are certainly warranted to overcome this exasperating sexual dysfunction. Abbreviations: AIPE: Arabic Index of Premature Ejaculation; CNS: central nervous system; CYP: cytochrome P450; ED: erectile dysfunction; FDA: United States Food and Drug Administration; H1: histamine receptors; 5-HT: 5-hydroxytryptamine; IELT: The intravaginal ejaculation latency time; IPE: Index of Premature Ejaculation; M1: muscarinic receptors; OCD: obsessive–compulsive disorder; PDE5: phosphodiesterase type 5; PE: premature ejaculation; PEP: Premature Ejaculation Profile; PRO: patient-reported outcome; RCT: randomised controlled trial; SS: Severance Secret (cream); SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants Premature ejaculation (PE) is perhaps the most common sexual dysfunction amongst men. The prevalence rate of PE is variable, but it is believed that one out of three men may complain of this sexual dysfunction at some point during their lives [Citation1].
This disease entity has suffered from significant ambiguities in the past with respect to its definition and pathophysiology, and it was not until 2014 when the first standardised evidence-based definition of PE was established [Citation2]. The evaluation of patients presenting with PE is initiated with a complete medical history looking for comorbidities that would make them prone to this clinical condition or would rather alter the offered treatment options (e.g. endocrine, urological, or psychorelational/psychosexual) [Citation3,Citation4] (). A detailed sexual history is obviously relevant to assess the frequency and nature of sexual encounters and to identify sexual comorbidities (e.g. erectile dysfunction [ED]) that would render PE simple (occurring in the absence of other sexual dysfunctions) or complicated (occurring in the presence of other sexual dysfunctions) [Citation3]. A literature search was conducted using the PubMed database searching for articles exploring different PE treatment modalities. A Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) approach was used to report the results of the literature search. A total of 149 articles were included in this review. The currently available treatment methods for PE include behavioural therapy, local anaesthetics, tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective phosphodiesterase inhibitors. Most PE treatments are either experimental or used off-label.
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New treatments are certainly warranted to overcome this exasperating sexual dysfunction. Abbreviations: AIPE: Arabic Index of Premature Ejaculation; CNS: central nervous system; CYP: cytochrome P450; ED: erectile dysfunction; FDA: United States Food and Drug Administration; H1: histamine receptors; 5-HT: 5-hydroxytryptamine; IELT: The intravaginal ejaculation latency time; IPE: Index of Premature Ejaculation; M1: muscarinic receptors; OCD: obsessive–compulsive disorder; PDE5: phosphodiesterase type 5; PE: premature ejaculation; PEP: Premature Ejaculation Profile; PRO: patient-reported outcome; RCT: randomised controlled trial; SS: Severance Secret (cream); SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants Premature ejaculation (PE) is perhaps the most common sexual dysfunction amongst men. The prevalence rate of PE is variable, but it is believed that one out of three men may complain of this sexual dysfunction at some point during their lives [Citation1].
This disease entity has suffered from significant ambiguities in the past with respect to its definition and pathophysiology, and it was not until 2014 when the first standardised evidence-based definition of PE was established [Citation2]. The evaluation of patients presenting with PE is initiated with a complete medical history looking for comorbidities that would make them prone to this clinical condition or would rather alter the offered treatment options (e.g.
The man relaxes on his back and the wife starts to stimulate his penis. When the man indicates high arousal and orgasm is about to occur, the woman stops stimulation and applies a firm squeeze to the head of the penis for 5–10 s with the thumb on the frenulum and the index and middle fingers just above the coronal ridge on opposite side until the man feels that the ejaculation reflex is inhibited. The female repeats the technique again two or three times and then the man proceeds to ejaculation. After several times of this practice, the male will be more able to control his ejaculation and gains confidence. The couple is instructed to start with the ‘woman-on-top’ position of intercourse.
The man lies on his back and the wife sits on top of him. Once he has a firm erection, he inserts his penis into her vagina, with his hands on her thighs to guide her movement. He asks her to stop moving once ejaculation is about to occur. She can start moving when the man’s arousal subsides a little and so on. The aim is to tolerate penetration without ejaculation for ~15 min.
If the man is initially unable to do so, he should not worry; he just needs to repeat the exercise as often as he needs. Once he can control his ejaculation, the couple can make love in any position they like [Citation13]. This technique is more preferable and similar to the above one except that the female stops stimulation only and does not apply squeeze to the glans penis when the orgasm is about to occur. When the male assumes control with the hand of his partner, intercourse can be done, with the female on top, then lateral, and finally male on top position. At all times coitus is stopped near orgasm until control is possible [Citation12]. endocrine, urological, or psychorelational/psychosexual) [Citation3,Citation4] (). A detailed sexual history is obviously relevant to assess the frequency and nature of sexual encounters and to identify sexual comorbidities (e.g. erectile dysfunction [ED]) that would render PE simple (occurring in the absence of other sexual dysfunctions) or complicated (occurring in the presence of other sexual dysfunctions) [Citation3]. The International Society for Sexual Medicine (ISSM) guidelines on PE recommends asking patients with such a presentation about the time between penetration and ejaculation (‘cumming’), their ability to delay ejaculation and the impact of such condition on their psychological wellbeing [Citation5]. It is also imperative to classify PE based on its onset into either lifelong or acquired PE and to assess the severity of the symptoms. Involving the partner during the initial and subsequent interviews is preferred to determine their view of the situation and the impact of PE and its treatment outcome on the couple as a whole. A genital examination is also recommended to evaluate the phallus and scrotal contents. In addition, assessment of patients with PE includes the use of validated questionnaires and patient-reported outcome (PRO) measures (the ability to have control over ejaculation and the extent of patient and partner sexual satisfaction) in addition to stopwatch measures of ejaculatory latency. Stopwatch measures of intravaginal ejaculatory latency time (IELT) were widely used in clinical trials and observational studies of PE, but have not been recommended for use in routine clinical management of PE [Citation6]. Despite the potential advantage of objective measurement, stopwatch measures have the disadvantage of being intrusive and potentially disruptive of sexual pleasure or spontaneity. Five validated questionnaires have been developed and published to date. Two measures (Index of Premature Ejaculation [IPE] and Premature Ejaculation Profile [PEP]) have premature ejaculation treatment extensive databases. One measure (PE Diagnostic Tool) has a modest database. Two other measures (Arabic and Chinese PE Questionnaires) have few clinical trial data available [Citation6]. Currently, no therapy is approved by the United States Food and Drug Administration (FDA) for treatment of PE [Citation7–9]. However, several therapies for PE are marketed and used in many countries. Treatment modalities as recommended by the British Association of Sexual Health and HIV include behavioural therapy, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), local anaesthetic agents, and phosphodiesterase type 5 (PDE5) inhibitors [Citation10] (). Numerous studies have shown that SSRIs and drugs with SSRI-like side-effects are safe and effective in the treatment of PE [Citation11]. The aim of the present review was to explore the various therapeutic options available for PE and highlight their mechanism(s) of action, effectiveness, advantages, and limitations. This review was conducted according to Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) criteria. The PubMed database was searched using the key words ((‘premature ejaculation’)) AND ((‘treatment’ OR ‘management’)) from the time of its initiation until 10 January 2021. The following filters were applied to the searched results: (1) Humans, (2) English, (3) Male, and (4) Adults (aged >18 years). Screening of the searched articles’ titles, abstracts and main text was performed successively. Reviews, commentaries, editorials, abstracts, and case reports were excluded from this review.
| Aspect | Description | Notes |
|---|---|---|
| PDE5 Inhibition | Vardenafil inhibits phosphodiesterase type 5 enzyme | Leads to increased blood flow and vascular relaxation |
| Nitric Oxide Role | Stimulates nitric oxide release to facilitate vasodilation | Enhances erectile response |
| Delay of Ejaculation | Indirectly prolongs time to ejaculation | Through improved erectile control |
| Absorption Rate | Fast onset within 30-60 minutes | Peak plasma concentration at ~1 hour |
Articles not specifically designed to investigate a PE treatment modality were also excluded; these constituted studies exploring PE aetiology, epidemiology, pathophysiology, psychological impact etc. Relevant articles were selected for inclusion in the discussion of various PE treatment modalities in this review (). A total of 1029 articles were initially retrieved with the literature search, and 814 articles were excluded after removing duplicates and applying the search filters and exclusion criteria. Additionally, 35 articles did not meet the main objective of the search and were excluded leaving 149 ed gel studies that were included in the discussion of this manuscript. Various treatment methods for PE have been described and include the following (). The two most frequently used techniques in behavioural therapy are the ‘stop-and-start’ technique described by Semans in 1956 [Citation12], and the ‘squeeze’ method developed by Masters and Johnson in 1970 [Citation13]. These techniques were proven to be effective in most cases. However, couples can be averse to using them, with some women reluctant to squeeze their partner’s penis and some couples unwilling to interrupt sexual interaction once initiated [Citation14]. These techniques focus on distraction and reduction of sexual excitement or stimulation, which may reduce overall sexual satisfaction. The man relaxes on his back and the wife starts to stimulate his penis. When the man indicates high arousal and orgasm is about to occur, the woman stops stimulation and applies a firm squeeze to the head of the penis for 5–10 s with the thumb on the frenulum and the index and middle fingers just above the coronal ridge on opposite side until the man feels that the ejaculation reflex is inhibited.
The aim of the present review was to explore the various therapeutic options available for PE and highlight their mechanism(s) of action, effectiveness, advantages, and limitations. This review was conducted according to Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) criteria. The PubMed database was searched using the key words ((‘premature ejaculation’)) AND ((‘treatment’ OR ‘management’)) from the time of its initiation until 10 January 2021. The following filters were applied to the searched results: (1) Humans, (2) English, (3) Male, and (4) Adults (aged >18 years). Screening of the searched articles’ titles, abstracts and main text was performed successively.
Reviews, commentaries, editorials, abstracts, and case reports were excluded from this review. Articles not specifically designed to investigate a PE treatment modality were also excluded; these constituted studies exploring PE aetiology, epidemiology, pathophysiology, psychological impact etc. Relevant articles were selected for inclusion in the discussion of various PE treatment modalities in this review (). A total of 1029 articles were initially retrieved with the literature search, and 814 articles were excluded after removing duplicates and applying the search filters and exclusion criteria. Additionally, 35 articles did not meet the main objective of the search and were excluded leaving 149 ed gel studies that were included in the discussion of this manuscript.
Various treatment methods for PE have been described and include the following (). The two most frequently used techniques in behavioural therapy are the ‘stop-and-start’ technique described by Semans in 1956 [Citation12], and the ‘squeeze’ method developed by Masters and Johnson in 1970 [Citation13]. These techniques were proven to be effective in most cases. However, couples can be averse to using them, with some women reluctant to squeeze their partner’s penis and some couples unwilling to interrupt sexual interaction once initiated [Citation14]. These techniques focus on distraction and reduction of sexual excitement or stimulation, which may reduce overall sexual satisfaction. The female repeats the technique again two or three times and then the man proceeds to ejaculation. After several times of this practice, the male will be more able to control his ejaculation and gains confidence. The couple is instructed to start with the ‘woman-on-top’ position of intercourse. The man lies on his back and the wife sits on top of him. Once he has a firm erection, he inserts his penis into her vagina, with his hands on her thighs to guide her movement. He asks her to stop moving once ejaculation is about to occur. She can start moving when the man’s arousal subsides a little and so on.
The aim is to tolerate penetration without ejaculation for ~15 min. If the man is initially unable to do so, he should not worry; he just needs to repeat the exercise as often as he needs.
Psychotherapy/behavioural interventions improve ejaculatory control by helping men/couples to: (1) learn techniques to control and/or delay ejaculation, (2) gain confidence in their sexual performance, (3) lessen performance anxiety, (4) modify rigid sexual repertoires, (5) surmount barriers to intimacy, (6) resolve interpersonal issues that precipitate and maintain the dysfunction, (7) come to terms with feelings/thoughts that interfere with sexual function, and (8) increase communication [Citation15–17]. Masters and Johnson [Citation13] reported success rate of up to 98% of men with PE treated with the start/stop and squeeze techniques at a 5-years follow-up. This has often, erroneously, been translated into a success rate. It has been reported that only 64% of patients successfully gained ejaculatory control using the squeeze technique, and only one-third showed continued control for 3 years after treatment [Citation18]. It was also found that men treated for PE using the same techniques experienced significant immediate benefits [Citation19]. Once he can control his ejaculation, the couple can make love in any position they like [Citation13]. This technique is more preferable and similar to the above one except that the female stops stimulation only and does not apply squeeze to the glans penis when the orgasm is about to occur. When the male assumes control with the hand of his partner, intercourse can be done, with the female on top, then lateral, and finally male on top position. At all times coitus is stopped near orgasm until control is possible [Citation12]. Psychotherapy/behavioural interventions improve ejaculatory control by helping men/couples to: (1) learn techniques to control and/or delay ejaculation, (2) gain confidence in their sexual performance, (3) lessen performance anxiety, (4) modify rigid sexual repertoires, (5) surmount barriers to intimacy, (6) resolve interpersonal issues that precipitate and maintain the dysfunction, (7) come to terms with feelings/thoughts that interfere with sexual function, and (8) increase communication [Citation15–17]. Masters and Johnson [Citation13] reported success rate of up to 98% of men with PE treated with the start/stop and squeeze techniques at a 5-years follow-up.
| Dose | Onset Time | Duration of Action | Adjustments | Precautions |
|---|---|---|---|---|
| 5 mg | 30-60 minutes | Up to 4-5 hours | For elderly or hepatic impairment | Avoid high-fat meals before intake |
| 10 mg | 30-60 minutes | Up to 4-5 hours | Standard dose | Do not exceed once per 24 hours |
| 20 mg | 30-60 minutes | Up to 6 hours | Not recommended for first use | Consult doctor for titration |
This has often, erroneously, been translated into a success rate.
The International Society for Sexual Medicine (ISSM) guidelines on PE recommends asking patients with such a presentation about the time between penetration and ejaculation (‘cumming’), their ability to delay ejaculation and the impact of such condition on their psychological wellbeing [Citation5]. It is also imperative to classify PE based on its onset into either lifelong or acquired PE and to assess the severity of the symptoms. Involving the partner during the initial and subsequent interviews is preferred to determine their view of the situation and the impact of PE and its treatment outcome on the couple as a whole. A genital examination is also recommended to evaluate the phallus and scrotal contents. In addition, assessment of patients with PE includes the use of validated questionnaires and patient-reported outcome (PRO) measures (the ability to have control over ejaculation and the extent of patient and partner sexual satisfaction) in addition to stopwatch measures of ejaculatory latency.
Stopwatch measures of intravaginal ejaculatory latency time (IELT) were widely used in clinical trials and observational studies of PE, but have not been recommended for use in routine clinical management of PE [Citation6]. Despite the potential advantage of objective measurement, stopwatch measures have the disadvantage of being intrusive and potentially disruptive of sexual pleasure or spontaneity. Five validated questionnaires have been developed and published to date. Two measures (Index of Premature Ejaculation [IPE] and Premature Ejaculation Profile [PEP]) have premature ejaculation treatment extensive databases. One measure (PE Diagnostic Tool) has a modest database.
Two other measures (Arabic and Chinese PE Questionnaires) have few clinical trial data available [Citation6]. Currently, no therapy is approved by the United States Food and Drug Administration (FDA) for treatment of PE [Citation7–9]. However, several therapies for PE are marketed and used in many countries. Treatment modalities as recommended by the British Association of Sexual Health and HIV include behavioural therapy, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), local anaesthetic agents, and phosphodiesterase type 5 (PDE5) inhibitors [Citation10] (). Numerous studies have shown that SSRIs and drugs with SSRI-like side-effects are safe and effective in the treatment of PE [Citation11]. It has been reported that only 64% of patients successfully gained ejaculatory control using the squeeze technique, and only one-third showed continued control for 3 years after treatment [Citation18]. It was also found that men treated for PE using the same techniques experienced significant immediate benefits [Citation19].