yulius hermanto
Pharmacotherapy for Premature Ejaculation
Introduction
Premature ejaculation (PE) is one of men's main concerns about his sexuality. Premature ejaculation often remains under-diagnosed and under-treated because of misperceptions by patients and physicians about its causes, lack of treatment modalities.
PE commonly occurs to a similar extent in men of all ages, compares to Erectile Dysfunction, that more often to be found in elderly.
PE is associated with short ejaculatory latency time, lack of ejaculatory control, decreased satisfaction of sexual intercourse, intrapersonal distress, a negative impact on a man’s self-esteem and reduced sexual function, and reduced quality of life. PE and ED as sexual dysfunction cause unsatisfaction sensation of sexual intercourse for man and his partner. Thus impact the relationship between both of them and give psychological pressure for man.
PE symptoms are not only about the time for ejaculation, but also involving ejaculatory control, satisfaction of sexual intercourse, distress, and interpersonal difficulty.
PE can be either a lifelong condition (present since the onset of sexual maturity) or an acquired condition that develops after an interval of normal sexual function.
Underlying mechanism in PE is not well-known, concept of negative conditioning and penile hypersensitivity have been proposed as aetiological factors in PE, but still not enough evidence to support that. Besides that, there are no recognized organic diseases that linked with PE compare with Erectile problems.
Notably, the physiology of ejaculation is often unimpaired in patients with PE, and it is the lack of voluntary control of, and the short time to ejaculation after vaginal penetration those the focus of the problem in PE.
It has been postulated that PE might have a sensory/neural component involving perturbations in the serotonergic (5-hydroxytryptamine, 5-HT) system, this concept could contribute in PE pathogenesis.
Physiology of ejaculation
Normal ejaculation involves the processes of emission and expulsion of semen, which are coordinated by a network of afferent and efferent neural pathways.
Tactile stimulation of glans penis and various stimuli at other sensual sites and brain imagination trigger an ejaculation process.
Our ejaculatory control centres are located within the spinal cord, and responsive to peripheral dan brain stimulation. And have major function to coordinate, the sympathetic, parasympathetic, and somatic outputs to the pelviperineal anatomical structures participating in the emission and expulsion phases.
Certain brain structures have been identified as related to sexual activity especially ejaculation process. In the brainstem, the nucleus paragigantocellularis, which contains a high concentration of serotonergic neurones, is shown to have a strong inhibitory role in the control of ejaculation. The periaqueductal grey has been shown, in an experimental animal system, to control the expulsion reflex.
Regulation of the ejaculatory reflex at the level of the spinal cord requires that coordinated neurochemical interrelationships take place at different levels of the neuraxis. Several neurotransmitter systems distributed throughout the supraspinal and spinal regions have been implicated in this process, with the 5-HT (serotonin) and dopaminergic neurones playing a primary role,
The neural pathways in ejaculation process is complex, involing many neurotransmitter and various neural structures, thus contributes to difficulty in determining of precise mechanism of ejaculation process.
Serotonin (5-HT) has risen scientists concern about its role in ejaculation process. Serotonin has several kind of receptor with different kind of action.
Activation of presynaptic serotonin neurons causes shorten in ejaculation latency. Serotonin stimulations to post-synaptics neurons causes prolong of ejaculation latency. Thus serotonin may play a major role in treatment.
Pharmacotherapy for PE
Pharmacotherapy or medical therapy can't guarantee an absolute cure for any kind of disease. But, with proper diagnosis and treatment perhaps it will give an optimal efforts in treating someone disease.
In modern era, pharmacotherapy is based on evidence based medicine or based on clinical trials measuring the efficacy of the proposed drugs, not by guessing or empirical.
Topical Agents
Topical lidocaine/prilocaine formulations are effectively cause desensitization, and have been shown to increase the mean in ejaculation latency in several trials. Mostly its effects on ejaculation related to desensitization of penis to stimuli, thus prolong the latency time for ejaculation. Side effects of this modality is numbness, burning sensation and rarely erection problem.
Sildenafil or Viagra
Sildenafil or viagra is shown doesn't have significant evidence in patient with PE, since it doesn't prolong the latency of ejaculation. But it can be used in combination with SSRI anti-depressants, especially in patients with concominant Premature ejaculation and erectile dysfunction. Viagra provides better sexual satisfaction and ejaculation control.
Clomipramine
Clomipramine is a tricyclic antidepressant that inhibits the uptake of noradrenaline and 5-HT by adrenergic and 5-HT neurones.
Continuous dosing with clomipramine significantly lengthened ejaculation latency compare with placebo.
After daily treatment with clomipramine, men with PE reported improved relationship and emotional satisfaction, men and their partners reported increased sexual satisfaction, and the partners reported an increased ability to achieve coital orgasm.
Usage of clomipramine in daily dosing might be limited by its associated side-effects. During continuous dosing, the adverse event of clomipramine in men with PE was reported to be significantly worse than with selective serotonin reuptake inhibitor (SSRI) treatment. Most annoying side-effects include sleepiness, yamning and nausea.
SSRIs antidepressants
Based on the role of serotonin in the physiology of ejaculatory control and possibly in the pathogenesis of PE, SSRIs antidepressants have become potential treatment for patient with premature ejaculation.
Currently marketed SSRIs such as paroxetine, fluoxetine, and sertraline, which increase synaptic Serotonin concentration via blockade of 5-HT transporters, have been investigated in numerous clinical studies for managing PE. The results are promising, SSRIs prolong ejaculation and give better sexual satisfaction than previous generation clomipramine.
American Urologic Association published current guidelines and recommendation for management of PE, and admitted SSRIs for PE treatment.
The Side-effects have been a major concern with the chronic use of SSRIs in patients with depressive disorders/symptoms, many of which have prompted discontinuation from therapy. The adverse effects of SSRIs include psychiatric and neurological consequences, dermatological reactions, anticholinergic
side-effects, changes in body weight, cognitive impairment.
Considering the shortcomings of chronic SSRI treatment, an optimal therapy for PE would have a short duration of activity, with clinical efficacy after each dose for on-demand treatment with no need for lead-in dosing.
Conclusion
Premature ejaculation is major concern of sexual medicine, not only for male but also for female. Inability to get sexual satisfaction will give a bad consequences of daily live, such as relationship problem with partner, depressed, loss of self-esteem, and poor quality of live.
Eventhough, premature ejaculation has a lot of consequences not only physical but also psychological and social, many patients still under-diagnosed and under-treated.
Pharmacotherapy using drugs doesn't guarantee 100% cure for any kind of disease, but it guarantee the best efforts of human knowledge to cure the disease.
SSRIs usage in treatment PE is promising, since its role in ejaculation is well described, but side-effects of chronic usage become the problem.
Proper dosing and short duration of activity SSRIs maybe an optional treatment in the future to overcome side-effects of SSRI.
Source: British Journal of Urology International 2008
Premature ejaculation (PE) is one of men's main concerns about his sexuality. Premature ejaculation often remains under-diagnosed and under-treated because of misperceptions by patients and physicians about its causes, lack of treatment modalities.
PE commonly occurs to a similar extent in men of all ages, compares to Erectile Dysfunction, that more often to be found in elderly.
PE is associated with short ejaculatory latency time, lack of ejaculatory control, decreased satisfaction of sexual intercourse, intrapersonal distress, a negative impact on a man’s self-esteem and reduced sexual function, and reduced quality of life. PE and ED as sexual dysfunction cause unsatisfaction sensation of sexual intercourse for man and his partner. Thus impact the relationship between both of them and give psychological pressure for man.
adopted from http://male-ejaculation.net
PE symptoms are not only about the time for ejaculation, but also involving ejaculatory control, satisfaction of sexual intercourse, distress, and interpersonal difficulty.
PE can be either a lifelong condition (present since the onset of sexual maturity) or an acquired condition that develops after an interval of normal sexual function.
Underlying mechanism in PE is not well-known, concept of negative conditioning and penile hypersensitivity have been proposed as aetiological factors in PE, but still not enough evidence to support that. Besides that, there are no recognized organic diseases that linked with PE compare with Erectile problems.
Notably, the physiology of ejaculation is often unimpaired in patients with PE, and it is the lack of voluntary control of, and the short time to ejaculation after vaginal penetration those the focus of the problem in PE.
It has been postulated that PE might have a sensory/neural component involving perturbations in the serotonergic (5-hydroxytryptamine, 5-HT) system, this concept could contribute in PE pathogenesis.
Physiology of ejaculation
Normal ejaculation involves the processes of emission and expulsion of semen, which are coordinated by a network of afferent and efferent neural pathways.
Tactile stimulation of glans penis and various stimuli at other sensual sites and brain imagination trigger an ejaculation process.
Our ejaculatory control centres are located within the spinal cord, and responsive to peripheral dan brain stimulation. And have major function to coordinate, the sympathetic, parasympathetic, and somatic outputs to the pelviperineal anatomical structures participating in the emission and expulsion phases.
adopted from http://www.sciencedaily.com
Certain brain structures have been identified as related to sexual activity especially ejaculation process. In the brainstem, the nucleus paragigantocellularis, which contains a high concentration of serotonergic neurones, is shown to have a strong inhibitory role in the control of ejaculation. The periaqueductal grey has been shown, in an experimental animal system, to control the expulsion reflex.
Regulation of the ejaculatory reflex at the level of the spinal cord requires that coordinated neurochemical interrelationships take place at different levels of the neuraxis. Several neurotransmitter systems distributed throughout the supraspinal and spinal regions have been implicated in this process, with the 5-HT (serotonin) and dopaminergic neurones playing a primary role,
The neural pathways in ejaculation process is complex, involing many neurotransmitter and various neural structures, thus contributes to difficulty in determining of precise mechanism of ejaculation process.
Serotonin (5-HT) has risen scientists concern about its role in ejaculation process. Serotonin has several kind of receptor with different kind of action.
Activation of presynaptic serotonin neurons causes shorten in ejaculation latency. Serotonin stimulations to post-synaptics neurons causes prolong of ejaculation latency. Thus serotonin may play a major role in treatment.
Pharmacotherapy for PE
Pharmacotherapy or medical therapy can't guarantee an absolute cure for any kind of disease. But, with proper diagnosis and treatment perhaps it will give an optimal efforts in treating someone disease.
In modern era, pharmacotherapy is based on evidence based medicine or based on clinical trials measuring the efficacy of the proposed drugs, not by guessing or empirical.
Topical Agents
Topical lidocaine/prilocaine formulations are effectively cause desensitization, and have been shown to increase the mean in ejaculation latency in several trials. Mostly its effects on ejaculation related to desensitization of penis to stimuli, thus prolong the latency time for ejaculation. Side effects of this modality is numbness, burning sensation and rarely erection problem.
Sildenafil or Viagra
Sildenafil or viagra is shown doesn't have significant evidence in patient with PE, since it doesn't prolong the latency of ejaculation. But it can be used in combination with SSRI anti-depressants, especially in patients with concominant Premature ejaculation and erectile dysfunction. Viagra provides better sexual satisfaction and ejaculation control.
Clomipramine
Clomipramine is a tricyclic antidepressant that inhibits the uptake of noradrenaline and 5-HT by adrenergic and 5-HT neurones.
Continuous dosing with clomipramine significantly lengthened ejaculation latency compare with placebo.
After daily treatment with clomipramine, men with PE reported improved relationship and emotional satisfaction, men and their partners reported increased sexual satisfaction, and the partners reported an increased ability to achieve coital orgasm.
Usage of clomipramine in daily dosing might be limited by its associated side-effects. During continuous dosing, the adverse event of clomipramine in men with PE was reported to be significantly worse than with selective serotonin reuptake inhibitor (SSRI) treatment. Most annoying side-effects include sleepiness, yamning and nausea.
SSRIs antidepressants
Based on the role of serotonin in the physiology of ejaculatory control and possibly in the pathogenesis of PE, SSRIs antidepressants have become potential treatment for patient with premature ejaculation.
Currently marketed SSRIs such as paroxetine, fluoxetine, and sertraline, which increase synaptic Serotonin concentration via blockade of 5-HT transporters, have been investigated in numerous clinical studies for managing PE. The results are promising, SSRIs prolong ejaculation and give better sexual satisfaction than previous generation clomipramine.
American Urologic Association published current guidelines and recommendation for management of PE, and admitted SSRIs for PE treatment.
The Side-effects have been a major concern with the chronic use of SSRIs in patients with depressive disorders/symptoms, many of which have prompted discontinuation from therapy. The adverse effects of SSRIs include psychiatric and neurological consequences, dermatological reactions, anticholinergic
side-effects, changes in body weight, cognitive impairment.
Considering the shortcomings of chronic SSRI treatment, an optimal therapy for PE would have a short duration of activity, with clinical efficacy after each dose for on-demand treatment with no need for lead-in dosing.
adopted from http://www.powerbro.com/
Conclusion
Premature ejaculation is major concern of sexual medicine, not only for male but also for female. Inability to get sexual satisfaction will give a bad consequences of daily live, such as relationship problem with partner, depressed, loss of self-esteem, and poor quality of live.
Eventhough, premature ejaculation has a lot of consequences not only physical but also psychological and social, many patients still under-diagnosed and under-treated.
Pharmacotherapy using drugs doesn't guarantee 100% cure for any kind of disease, but it guarantee the best efforts of human knowledge to cure the disease.
SSRIs usage in treatment PE is promising, since its role in ejaculation is well described, but side-effects of chronic usage become the problem.
Proper dosing and short duration of activity SSRIs maybe an optional treatment in the future to overcome side-effects of SSRI.
Source: British Journal of Urology International 2008
