madman
Super Moderator
ABSTRACT
To analyze 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 behavioral therapy, local anesthetics, 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.
Introduction
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 [1]. 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 standardized evidence-based definition of PE was established [2].
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) [3,4] (Table 1). 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) [3]. 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 [5].
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 the 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 the routine clinical management of PE [6]. 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 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 [6].
Currently, no therapy is approved by the United States Food and Drug Administration (FDA) for the treatment of PE [7–9]. 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 behavioral therapy, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), local anesthetic agents, and phosphodiesterase type 5 (PDE5) inhibitors [10] (Table 2). Numerous studies have shown that SSRIs and drugs with SSRI-like side effects are safe and effective in the treatment of PE [11]. 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.
Behavioral therapy
1. Squeeze technique
2. Start/stop technique
The goals of traditional psychotherapy/behavioral interventions
The effectiveness of the start/stop and squeeze techniques
Pharmacological interventions (Table 3)
1. Tricyclic antidepressants (TCAs)
*Clomipramine
-Mechanism of action and efficacy of clomipramine in the treatment of PE
-Drug interactions
2. Selective serotonin reuptake inhibitors (SSRIs)
Methods of administration of SSRIs
1. Acute SSRI administration
2. Chronic SSRI administration
Limitations associated with SSRIs
*Fluoxetine
-Efficacy of fluoxetine in the treatment of PE
*Citalopram
-Efficacy of citalopram in the treatment of PE
*Escitalopram
-Efficacy of escitalopram in the treatment of PE
*Sertraline
-Efficacy of sertraline in the treatment of PE
*Paroxetine hydrochloride
-Efficacy of paroxetine in the treatment of PE
*Fluvoxamine
-Efficacy of fluvoxamine in the treatment of PE
*Dapoxetine
-Efficacy of dapoxetine in the treatment of PE
SSRI drug interactions
Topical therapy (anesthetics)
A. Lidocaine-prilocaine 5% cream
B. Local Severance Secret (SS) cream
C. Lidocaine-prilocaine spray
D. Dyclonine/alprostadil cream
Phosphodiesterase type 5 inhibitors
Opioid agonist
Surgical treatments
a. Glans augmentation
b. Dorsal neurectomy
c. Pulsed radiofrequency neuromodulation
d. Frenectomy
e. Surgical removal of foreskin remnants
f. Varicocelectomy
Other treatment
A. Adrenergic nerve blockade
B. Folic acid
C. Caffeine
D. Injections of botulinum toxin (A RCT using rat models)
Conclusions
Premature ejaculation is a commonly encountered male sexual dysfunction, with a potential negative impact on the patient and his partner. In the present review, we explored the different therapeutic approaches that are currently available for the treatment of PE including behavioral, pharmacological, and surgical options. Interestingly, the medications currently used in the treatment of PE are sold off-label. Except for the newly licensed dapoxetine, which provides an effective, on-demand treatment regimen with relatively minimal side effects, it is not clear whether it received final FDA approval for treatment of PE. Therefore, it is important for the clinician to recognize all PE treatment options as each patient may respond differently and experience variable side effects. Future efforts should be directed towards understanding the exact pathophysiology of PE at different clinical setups and developing additional therapies with higher efficacy and minimal or no adverse effects.
To analyze 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 behavioral therapy, local anesthetics, 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.
Introduction
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 [1]. 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 standardized evidence-based definition of PE was established [2].
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) [3,4] (Table 1). 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) [3]. 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 [5].
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 the 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 the routine clinical management of PE [6]. 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 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 [6].
Currently, no therapy is approved by the United States Food and Drug Administration (FDA) for the treatment of PE [7–9]. 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 behavioral therapy, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), local anesthetic agents, and phosphodiesterase type 5 (PDE5) inhibitors [10] (Table 2). Numerous studies have shown that SSRIs and drugs with SSRI-like side effects are safe and effective in the treatment of PE [11]. 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.
Behavioral therapy
1. Squeeze technique
2. Start/stop technique
The goals of traditional psychotherapy/behavioral interventions
The effectiveness of the start/stop and squeeze techniques
Pharmacological interventions (Table 3)
1. Tricyclic antidepressants (TCAs)
*Clomipramine
-Mechanism of action and efficacy of clomipramine in the treatment of PE
-Drug interactions
2. Selective serotonin reuptake inhibitors (SSRIs)
Methods of administration of SSRIs
1. Acute SSRI administration
2. Chronic SSRI administration
Limitations associated with SSRIs
*Fluoxetine
-Efficacy of fluoxetine in the treatment of PE
*Citalopram
-Efficacy of citalopram in the treatment of PE
*Escitalopram
-Efficacy of escitalopram in the treatment of PE
*Sertraline
-Efficacy of sertraline in the treatment of PE
*Paroxetine hydrochloride
-Efficacy of paroxetine in the treatment of PE
*Fluvoxamine
-Efficacy of fluvoxamine in the treatment of PE
*Dapoxetine
-Efficacy of dapoxetine in the treatment of PE
SSRI drug interactions
Topical therapy (anesthetics)
A. Lidocaine-prilocaine 5% cream
B. Local Severance Secret (SS) cream
C. Lidocaine-prilocaine spray
D. Dyclonine/alprostadil cream
Phosphodiesterase type 5 inhibitors
Opioid agonist
Surgical treatments
a. Glans augmentation
b. Dorsal neurectomy
c. Pulsed radiofrequency neuromodulation
d. Frenectomy
e. Surgical removal of foreskin remnants
f. Varicocelectomy
Other treatment
A. Adrenergic nerve blockade
B. Folic acid
C. Caffeine
D. Injections of botulinum toxin (A RCT using rat models)
Conclusions
Premature ejaculation is a commonly encountered male sexual dysfunction, with a potential negative impact on the patient and his partner. In the present review, we explored the different therapeutic approaches that are currently available for the treatment of PE including behavioral, pharmacological, and surgical options. Interestingly, the medications currently used in the treatment of PE are sold off-label. Except for the newly licensed dapoxetine, which provides an effective, on-demand treatment regimen with relatively minimal side effects, it is not clear whether it received final FDA approval for treatment of PE. Therefore, it is important for the clinician to recognize all PE treatment options as each patient may respond differently and experience variable side effects. Future efforts should be directed towards understanding the exact pathophysiology of PE at different clinical setups and developing additional therapies with higher efficacy and minimal or no adverse effects.
