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Home , Dapoxetine, Retrograde ejaculation

FEATURE Ejaculatory dysfunction: a review of current practice and guidelines

BY JASKARN RAI AND JONATHAN CHARLES GODDARD

Introduction motor centres and efferent pathways and bulbocavernosus muscles and of The ejaculatory process is paramount (Figure 1). This multifaceted interplay the pelvic floor expelling the to procreation in nature. It is a complex results in emission and expulsion with with enough force to exit the . orchestration of physiology that results . The external urethral sphincter relaxes in emission of the ejaculate into the Initial stimulation of the Krause- and the bladder neck closes resulting in posterior urethra followed by ejection Finger corpuscles in the glans mucosa antegrade . of those fluids from the urethra and of the results in reflex activation The pressure increase in the orgasm. The study of ejaculation is a once a threshold has been achieved. posterior urethra is relayed through recent innovation within the field of This sensory information is transmitted the sensory pudendal afferents in medicine, with research in the last few via the dorsal of the penis (S4) to association with sensory stimuli decades revealing the true complexity the lumbosacral spinal cord combining from the verumontanum, urethral of both normal and abnormal with sympathetic afferents from the contraction and input from secondary pathways. Public and professional hypogastric plexus. This combined sexual organs. After central processing awareness of male input ascends the cord and receives this results in orgasm. has increased in part due to the rise in further visual, auditory and olfactory phosphodiesterase inhibitor use for input in the cerebrum. . The old belief of This multi-sensory input then has This was first described by Shapiro in sexual dysfunction lying purely within to be co-ordinated by the forebrain 1947 and was divided into two types the domain of the aged man has been to form the complex of copulatory which were later termed lifelong shattered. Lauman’s study of 1410 behaviours. These forebrain structures and acquired. The prevalence of men aged 18-59 years revealed sexual include the medial pre-optic area (MPA) lifelong or chronic PE is about 30% [1]. dysfunction in up to 31% [1]. More and the para-ventricular nucleus (PVN) Acquired PE may come on gradually or recent studies show similar results with of the hypothalamus. suddenly but is preceded by a normal estimates of sexual dysfunction in up to There are several neurotransmitters intravaginal ejaculatory latency time 28% [2]. involved in the central ejaculatory (IELT). Sexual dysfunction encompasses pathway and in the last decade their The International Society for Sexual hypogonadism (primary and role has become clearer. Dopamine Medicine definition (2007) for PE secondary), erectile dysfunction and levels increase during sexual excitation is IELT of less than one minute for ejaculatory dysfunction. The most and this in turn has an excitatory role lifelong PE. For acquired PE, where common of these is ejaculatory on ejaculation (via D2 receptors) [3]. the man had previously experienced dysfunction, which can affect up to 14% GABA-receptor antagonists have normal intravaginal latency times the of men [2]. demonstrated sexual inhibition in definition has been recently defined as Ejaculatory dysfunction can manifest animal models. mediates a clinically significant and bothersome as a spectrum that ranges from the the muscular contraction involved in reduction in latency time, often to most common, premature ejaculation ejaculation. The double-edged sword of about three minutes [7]. This involves (PE), through to the lesser seen delayed (5-Hydroxytryptamine-HT) negative personal consequences such and absent ejaculation (anejaculation). has both an inhibitory role via 5-HT2C as distress, and bother. In In retrograde ejaculation the ejaculate receptors and an excitatory role via severe cases it may lead to avoidance of does not enter the posterior urethra 5-HT1A receptors [4,5]. Nitric oxides intercourse completely. but retro pulses into the bladder only modulates seminal emission [6]. The prevalence of PE can be as to exit the urethra with the next urinary The sympathetic efferents (T10-L2) high as 30% from the global study void. Whereas PE is largely thought to conduct the emission aspect of the of sexual attitudes and behaviours arise from psychological pathology, AE reflex. These activated fibres curve in men over 40 [2]. Although, due to and RE are mainly due to an organic over the pelvic brim to the pelvic plexus relative inconsistency of symptoms and cause. and result in sequential contraction of degree of bother, the true prevalence is the , , seminal difficult to measure. Normal ejaculatory vesicle and with co-ordinated physiology closure of the bladder neck. Causes of PE The normal ejaculatory process is a The somatically driven pudendal For lifelong PE Waldinger proposed complex interplay between sensory nerve initiates the expulsion or ejection central serotinergic dysfunction as receptors, afferent pathways, cerebral phase (S2-S4) resulting in rhythmic the causative agent, being either a sensory and motor centres, spinal contractions of the bulbospongiosus hyposensitivity of the 5-HT2C and or

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hypersensitivity of the 5-HT1A receptor and not a psychological problem [8]. In acquired PE the causes can be psychosexual or relationship-based issues but they may also be organic in nature too, such as erectile dysfunction, or thyroid dysfunction.

Non-pharmacological treatment of premature ejaculation The treatment of PE is dependent on the type – lifelong or acquired – and the likely cause. Urological issues and thyroid problems need to be managed appropriately. If there is a psychological element then it too needs addressing. Men with PE are often racked with feelings of guilt and failure, which in turn leads to worry and tension. Relative to men without PE they also have decreased self-confidence and are overly occupied with their ejaculation. This can often lead to relationship dysfunction [9]. Present day psychotherapy embodies the concepts of behavioural techniques such as stop-start and pause-squeeze methods [10] with cognitive approaches and short-term psychotherapy. Current thinking supports lifelong PE ejaculation as a neurobiological phenomenon based on animal models and not a psychological problem [8]. This strategy can be expensive and requires a specialty service to be set up for men to be referred. The benefits are plentiful, in that the techniques learned have no side-effects, have no impact on men’s other comorbidities Figure 1: the ejaculatory process. and are tailored to the individual’s situation. This also allows the man to communicate his sexuality with transporters. The stimulation of post- dysfunction and now also in male lower his partner and increase bonding. synaptic 5HT2c autoreceptors, [12] urinary tract obstruction. Initial reports The techniques can be used again for in respect of , , of their use in the treatment of PE were current and future relationships as and not encouraging [15] but more recent necessary. has also been researched. Paroxetine studies have shown them to have a shows the greatest ejaculation delay favourable effect in increasing the IELT Pharmacotherapy for (8.8 fold increase over placebo) [13]. compared to placebo [16]. premature ejaculation Men treated with SSRIs should be The use of both an SSRI and a Topical anaesthesia can be used counselled as to the risk of adverse phosphodiesterase inhibitor (PDE5) directly on to the glans penis, however events and withdrawal. Currently daily has been explored but remains a this must be worn with a condom lest SSRIs are off licence for use in PE. contraindication because of the PDE5 vaginal anaesthesia occur. Studies One of the newer shorter acting interaction with CYP2D6 inhibitors using TEMPE® (eutectic mixture of SSRIs, dapoxetine, has been shown (with a likely increase in adverse prilocaine and lidocaine, Plethora UK), to have a lower incidence of adverse events as a result). The combination of showed an IELT 2.4 times higher than events and sexual dysfunction. dapoxetine with has shown an control with improvement in patient Dapoxetine as an on demand treatment increased IELT over dapoxetine alone and partner sexual quality of life [11]. was shown to have significantly [17]. Likewise, an increase in IELT has In recent years selective serotonin improved IELT and patient and partner been shown for paroxetine and reuptake inhibitors (SSRI) have sexual satisfaction [14]. Dapoxetine is [18]. In these studies men had PE only been demonstrated to block axonal the only SSRI licensed for the treatment (and without ED). The increased IELT re-uptake of serotonin from the of PE. with dapoxetine has been shown in synaptic cleft of central and peripheral Phosphodiesterase inhibitors are well men with ED and PE on a stable dose of serotonergic neurones by 5HT known for their role in treating erectile a PDE5 inhibitor with similar adverse

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“Ejaculatory Retrograde ejaculation bladder neck with bulking agents such Men who fail to ejaculate but as macroplastique has limited success. dysfunction is both attain orgasm may have a failure of ejaculation or retrograde ejaculation Anejaculation a common and (RE). In RE the is retropulsed into In extreme cases there may be the bladder through an open bladder complete failure of the muscles debilitating problem neck due to the failure of the bladder involved in emission resulting in for men of all ages.” neck closure. The bladder neck is anejaculation. This is more often seen contracted by sympathetic activation of in patients [26] the α-adrenoreceptors. This can occur but can also been seen after radical during pharmacotherapy for bladder surgery of the pelvis. Fertility may outflow obstruction particularly with be restored with the use of a penile the uroselective α-blocker in vibrator / electro ejaculator [27]. In up to 30% [21]. It is less of an issue with those not responding to penile vibratory events to those on a PDE5 inhibitor other alpha blockers. techniques or in non spinal cord injury alone [19].This would suggest that PDE5 Bladder neck incision and anejaculation men, then surgical sperm inhibitors have a potential use in PE in transurethral resection of prostate retrieval and intracytoplasmic sperm men with and without ED and that this will surgically disrupt the bladder neck insemination are suitable alternatives. is more effective in combination with muscle fibres preventing them from an SSRI such as dapoxetine. However closing during ejaculation. The rate of Painful ejaculation at present, combination treatment RE after this type of surgery is up to This is an uncommon problem and can with depoxetine and a PDE5i is still 80% [22]. This point needs to be very also have a psychological or organic contraindicated under the UK licence. clearly explained during the consenting cause. Acute and chronic prostatitis Other pharmacological approaches process particularly in men requiring can lead to painful ejaculation. which have failed to show significant surgery before completing their family. Treatment of the prostatitis or results for PE include , A1 Newer techniques with laser prostate other underlying cause of the pain is adrenoreceptor antagonists and penile resection may have less RE [23] and required. Other pathology that can injection therapy. certainly new technologies such as cause painful ejaculation includes Upon seeing a man with PE in the the Urolift™ have been developed to inflammation clinic the urologist should obtain preserve bladder neck closure [24]. obstruction, inflammation or stones in detailed medical and sexual history, Other surgical insults resulting in RE the ejaculatory duct. The latter two are physical examination and appropriate can occur during pelvic surgery where amenable to endoscopic resection. investigations i.e. thyroid function the hypogastric plexus crosses the tests, urine culture and sensitivity. If an pelvic brim and is susceptible to injury. Conclusion obvious organic cause of PE is found then This is relevant in retroperitoneal lymph Ejaculatory dysfunction is both a treatment is tailored accordingly. The node dissection for germ cell tumours, common and debilitating problem for patient will need to give an account of aorto-iliac surgery, and excision of the men of all ages. A simple approach the duration of the PE (acute or lifelong, rectum. These sympathetic fibres can to define the type of ejaculation as situation or global). A subjective account also be damaged as part of premature, retrograde or anejaculation of the IELT is taken from the patient mellitus, and spinal from the history establishes the likely and an assessment of the partner’s cord injury [25]. cause. Medical conditions will need to satisfaction made. The diagnosis of RE can be confirmed be optimised if implicated and causative Men with lifelong PE are usually best by testing the post ejaculation medication can be reviewed. Cognitive managed pharmacologically. In these void for fructose and spermatozoa behavioural therapy for PE should be instances a decision is made between and transrectal ultrasound (TRUS) used where appropriate. The medical the more potent daily SSRI, paroxetine visualisation of an open bladder neck treatment of PE should consider the use (10mg to 40mg daily) which is off- at rest. of topical therapy with local anaesthetic label and the on demand preparation agents and SSRIs either daily (but this is dapoxetine (30mg to 40mg one to two Treatment of retrograde an off license treatment) or on demand. hours before intercourse) which has ejaculation In retrograde ejaculation and less side-effects and which has a lower The management of RE may, in some anejaculation the restoration of risk of withdrawal (and is also the only cases, only require reassurance to the normal antegrade flow is unlikely licensed SSRI). Paroxetine, although man that there is no serious underlying to be achieved. If surgery is to be more effective, will take on average five pathology. Alpha-blockers can be undertaken with a high risk of RE in to seven days to increase IELT and can withdrawn or changed. An attempt to men who have not completed their in some cases take up to two to three close the bladder neck via α-adrenergic families then this should be borne in weeks. activation with pseudoephidrine or mind. Either a limited bladder neck Cognitive behavioural therapy (CBT) is using tricyclic such incision, or use of Urolift™, to limit RE likely to benefit any men with significant as with noradrenaline should be considered. Alternatively relationship factors that are contributing reuptake inhibitors action could be a uro-selective α-blocker other then to the PE. Acquired PE can be managed made. If the RE is inhibiting fertility, tamsulosin can be used and surgery with pharmacotherapy (dapoxetine) [20] semen can be extracted from the post deferred until the man has completed with added CBT for the couple. orgasmic voided urine. Augmenting the his family.

urology news | JANUARY/FEBRUARY 2015| VOL 19 NO 2 | www.urologynews.uk.com FEATURE

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