Retarded ejaculation in men: an overview of psychological and neurobiological insights

Disorders of orgasm and ejaculation are erroneously mixed up in the DSM-IV classification system. Male Orgasmic Disorder to denote delayed ejaculation is inadequate as orgasm and ejaculation represent clinical expressions of different neurobiological phenomena. Unfortunately, the DSM-IV criteria for delayed ejaculation were accepted regardless of any research with appropriate methodology and design. The psychological approach and associated psychotherapy to solve this problem is rather disappointing. The neurobiological approach, which started with animal studies, has demonstrated various neurotransmitters with the potency to inhibit ejaculation. Indeed, several experimental drugs have been tested in rats, showing the successful acceleration of ejaculation. We propose that human research should start with the development of an operational definition of delayed ejaculation. To achieve this goal, we propose unselected epidemiological stopwatch studies which also provide information on the prevalence and incidence of delayed ejaculation in men. Currently, no effective and safe drugs are available to accelerate ejaculation time in men. The best way to treat lifelong delayed ejaculation is, thus far, to inform the patients about biological and psychological inhibiting factors which they need to avoid, and to remain critical about unrealistic expectations from psychotherapy. Psychotherapy may be useful in subgroups, particularly in the absence of effective and safe drugs.     

The Effect of LUTS/BPH and Treatments on Ejaculatory Function

As men age, there is an increased incidence of lower urinary tract symptoms (LUTS), often from benign prostatic hyperplasia (BPH) which can adversely affect sexual function. There are many different treatments for these symptoms; however, many of the treatments also affect sexual quality of life, specifically in the realm of ejaculation. Our paper will review the medications, surgical procedures, minimally invasive procedures, and even investigational procedures used to treat LUTS/BPH and the effect they have on ejaculation. The aim of this paper is to help practitioners counsel patients more effectively on treatment options when ejaculation is a concern.     

Ejaculatory disorders: pathophysiology and management

Ejaculatory dysfunction (EjD) is one of the most common male sexual disorders, yet EjD is still frequently misdiagnosed or overlooked as a result of numerous patient and physician barriers. The wide spectrum of EjD ranges from premature or rapid ejaculation, through delayed ejaculation, to a complete inability to ejaculate--otherwise known as anejaculation--and includes retrograde ejaculation and painful ejaculation. Conventional algorithms for managing ejaculatory disorders are based either on an organic or psychogenic etiology, with the latter more traditionally considered the main cause. This paper reviews physiopathological, diagnostic and therapeutic aspects of ejaculation disorders, with a particular focus on the most prevalent disorder, premature ejaculation.     

Electromyographic study of ejaculatory mechanism

Cavernosus muscle (CM), seminal vesicle (SV) and vasal ampullary (VA) contractions at ejaculation are said to be reflex mechanisms (ejaculatory reflex), which have been scarcely dealt with in the literature. We investigated the hypothesis that contraction of the CMs, SVs and VA at ejaculation is a reflex action. The electromyographic (EMG) activity of CM, SV and VA during ejaculation was recorded in 28 healthy men. The test was repeated after separate anaesthetization of the glans penis (GP), CMs, SVs, and VA in the pre-ejaculatory period. Latent ejaculatory time (LET) was calculated. CMs showed no EMG activity until rigid erection phase was reached. SVs and VA exhibited resting EMG activity which increased gradually with different stages of erection. At ejaculation, CMs, SVs and VA showed two to four intermittent contractions. The mean LET was 1.3 ± 0.2 sec. GP anaesthetization led to the disappearance of CM, SV and VA EMG activity at ejaculation, while bland gel did not affect EMG activity. CMs, SVs and VA when anaesthetized in the pre-ejaculatory period exhibited no EMG activity at ejaculation, while saline did not affect EMG activity. Increased EMG activity of CM, SV and VA apparently denotes increase in their contractile activity. CM, SV and VA contraction on GP stimulation and ejaculation are assumed to be reflex actions and are mediated through the 'glans-cavernosovesicular reflex' (GCVR) which presumably represents the ejaculatory reflex. Changes in LET or evoked response would indicate a defect in the reflex pathway. The GCVR might act as an investigative tool in diagnosing erectile dysfunction, provided further studies are performed in this respect.     

Sexotherapy and disorders of ejaculation

The author reviews the disorders of ejaculation: premature ejaculation delayed ejaculation and retarded ejaculation. She proposes behavioral treatments adapted to each disorder: single techniques provide most often excellent results.     

Treatment of premature ejaculation

Premature ejaculation (PE) is the most common male sexual disorder, and it may have a profound negative impact on a man and his partner's lives. Different organizations and societies have no consensus on the definition and classifications of PE. However, most organizations and societies include in their definitions the intravaginal ejaculation latency time (IELT), the control of ejaculation, and the distress or impact of interpersonal difficulties. Evaluation procedures have been standardized in clinical studies by the development of an objective measurement of IELT (using a stopwatch) and by the introduction of patient-reported outcome (PRO) questionnaires on ejaculation control and sexual satisfaction. The identification of four different patterns of PE—lifelong, acquired, normal variant, and premature-like ejaculatory dysfunction—is critical because of different underlying pathogeneses and consequently different management approaches. The optimal treatment for PE should be individualized, based on a patient's symptoms, expectations, and underlying variant causes. Most lifelong PE patients need pharmacotherapy (possibly in combination with psychosexual counseling) as a first-line treatment because of the underlying neurobiological etiology and the impact of PE on the couple's relationship. The management of acquired PE is etiologically specific and may include pharmacotherapy for erectile function management in men with comorbid erectile dysfunction (ED). Men with natural variable PE complain of early ejaculation in situational or coincidental conditions; the ejaculation is inconsistent and occurs irregularly. Psychoeducation and reassurance are indicated for men with this type of PE. Psychotherapy or sex counseling is the first choice of treatment for men with premature-like ejaculatory dysfunction. All pharmacotherapies such as long-term selective serotonin reuptake inhibitors (SSRIs) or on-demand topical anesthetics are off-label indications, The benefits of pharmacotherapy toward improving ejaculation times should be weighed against their safety profiles. The development of the short-acting selective serotonin reuptake inhibitor (SSRI) dapoxetine hydrochloride (30 mg and 60 mg) for oral on-demand use opened a new era of PE treatment. Other potential pharmacotherapies such as tramadol, lidocaine/prilocaine spray, and phosphodiesterase inhibitors are still under development. Their safety and efficacy profiles should be further evaluated and supported by additional clinical studies.     

The relationship between premature ejaculation and the timing of pre-adult circumcision

We aimed to investigate the relationship between premature ejaculation and the age when men had been circumcised before adulthood. A total of 2,768 sexually active male patients aged between 18 and 65 years were included in this study. A multicentre study was conducted prospectively with the participation of 20 centres. A survey consisting of 12 questions prepared by the researchers, as well as the validated Turkish versions of the five-item Premature Ejaculation Diagnostic Tool, was administered to all participants. The study included 1,603 participants who met the inclusion criteria. There was no significant difference in the Premature Ejaculation Diagnostic Tool and self-reported ejaculation time between the participants who had been circumcised at different ages during childhood. Remembering circumcision experience with fear or anxiety did not increase the risk of sexual dysfunction compared to the participants who described their experience with happiness or with no particular emotion. There was no significant difference in Premature Ejaculation Diagnostic Tool scores or the self-reported ejaculation time of the participants circumcised at different ages. The age of childhood circumcision, having a fearful or anxious circumcision experience, does not affect the risk of premature ejaculation in adult life.     

522例早泄患者的勃起功能调查

目的 :了解早泄患者的勃起功能评分与其实际勃起能力。　方法 :采用中国男性勃起功能调查表 (CIEF 5 )问卷调查方式。　结果 :5 2 2例中自认为有ED者 341(6 5 .33% )例 ,4 33(82 .95 % )例CIEF评分低于正常值参考标准 ,自认为有无ED与CIEF评分间差异有显著性 ,有无早泄与自认为有无ED间差异有显著性。　结论 :早泄对勃起功能评分的正确性有显著的干扰作用 ,自认为有ED的早泄患者的勃起功能与CIEF 5评分有高度的吻合性 ,自认为无ED的早泄患者的勃起功能与CIEF 5评分存在较大差异 ,其中许多CIEF 5评分轻度降低可能为早泄引起而并非真正的ED者 ,而CIEF 5评分为中重度降低的早泄患者可能为同时合并ED者。对同时存在早泄与ED的年轻患者 ,在采用CIEF 5评分时 ,应特别考虑其主观感觉 ,并排除因早泄对问题 4、5对勃起功能评价可靠性的干扰     

Lifelong premature ejaculation: definition, serotonergic neurotransmission and drug treatment

The ejaculation distribution theory (EDT) postulates a biological continuum of the intravaginal ejaculation latency time (IELT) in men. Such an continuum has recently been found in two epidemiological stopwatch studies. In addition, a continuum of ejaculation latency time has also been demonstrated in laboratory rats. It is suggested that the invariable parts of ejaculation, i.e. premature and retarded ejaculation are highly influenced by genetic and neurobiological factors. In contrast, superimposed on biological roots, ejaculation of men, in the middle part of the continuum, is probably more easily influenced by environmental and psychological factors. A meta-analysis of 35 daily SSRI and clomipramine treatment studies demonstrated a similar efficacy for paroxetine, clomipramine, sertraline and fluoxetine, with paroxetine exerting the strongest effect on ejaculation. Based on fundamental insights into serotonergic neurotransmission, it is suggested that on-demand conventional SSRI treatment will not lead to similarly impressive ejaculation delay as that found after daily conventional SSRI treatment. Future studies with SSRIs with short half-lives, short T_max and high C_max should elucidate whether these pharmacokinetic properties are able to affect the pharmacodynamics of 5-HT neurons in such a way that immediate clinically relevant ejaculation delay occurs.     

Role of peripheral innervation in p-chloroamphetamine-induced ejaculation in anesthetized rats

The occurrence of ejaculation, which consists of 2 distinct phases (emission and expulsion), requires a tight coordination of peripheral autonomic and somatic nerves. However, some aspects of the mechanism of ejaculation are not clearly defined. To clarify this issue, we used the p-chloroamphetamine (PCA)-induced ejaculation model in anesthetized rats and investigated the effects of selective peripheral nerves lesions on seminal vesicle and bulbospongiosus (BS) muscle activities as representing physiological markers of emission and expulsion phases, respectively. In intact rats, ejaculation induced with PCA (intraperitoneal 5 mg/kg) correlated with coordinated increases in seminal vesicle pressure (SVP) and BS electromyographic activity. PCA-induced ejaculation was still observed in rats with bilateral lesion of hypogastric nerves (HNx), lumbar paravertebral sympathetic chain (LSCx), or dorsal nerves of the penis (DNPx). Conversely, bilateral section of pelvic nerves (PNx) or L6-S1 dorsal roots (DRx) abolished PCA-induced ejaculation. The amplitude of SVP increases induced by PCA was reduced in PNx, HNx, and LSCx rats, whereas it was unchanged in DRx and DNPx rats. The time interval between SVP increases and BS muscle contractions induced by PCA was comparable in the different neural lesion groups. In conclusion, PCA initiates both emission and expulsion independently from each other. In this model, afferents conveyed by the pelvic nerves appear to be unnecessary for occurrence of BS muscle contractions but are essential for a complete ejaculatory response.     

不同术式治疗前列腺增生症对性功能影响的观察

目的 比较3种不同术式治疗良性前列腺增生症(BPH)术后对性功能的影响。方法 对40例经尿道前列腺电切术(TURP)和60例耻骨上前列腺切除术(SPPC)与40例改良保留尿道前列腺切除术(MMPC)患者进行9个月的追踪观察，总结其术后勃起功能障碍(ED)及逆行射精发生率。结果 TURP组术后ED发生率增加了35％(14／40)，逆行射精的发生率为50％；SPPC组和MMPC组术后ED的发生率分别增加了为33．33％(20／60)、7．5％(3/40)，逆行射精的发生率分别为62．5％和16％。结论 在治疗前列腺增生症3种术式中，术后性功能损害MMPC组优于TURP组和SPPC组，逆行射精发生率MMPC组也优于其他术式。     

Pregnancy following treatment of retrograde ejaculation with clomipramine hydrochloride. A report of 3 cases

In 2 out of 3 cases of retrograde ejaculation treatment with clomipramine hydrochloride resulted in normal ejaculation and conception. The 3rd patient was only partially helped by the drug. The mechanisms of ejaculation, the causes of retrograde ejaculation, the management of the condition and the relevant pharmacological features of the tricyclic anti-depressants are discussed.     

Impact of medical treatments for benign prostatic hyperplasia on sexual function

Lower urinary tract symptoms (LUTS) and male sexual dysfunction are highly prevalent in ageing men, and are strongly linked. Various treatment strategies for benign prostatic hyperplasia (BPH)/LUTS may affect sexuality, with differences between drug classes and between drugs within a same class. The 5alpha-reductase inhibitors, finasteride and dutasteride, are associated with a greater risk of erectile dysfunction (ED), ejaculatory dysfunction (EjD) and decreased libido than is placebo. Alpha1-adrenoceptor blockers (alfuzosin, doxazosin, tamsulosin, terazosin) show an incidence of decreased libido and ED closely similar to placebo, but differ in their impact on ejaculation, tamsulosin being associated with a higher incidence of EjD (10%) than other alpha1-adrenoceptor blockers (0-1%) and placebo (1%), which is unrelated to retrograde ejaculation or higher efficacy. A randomized, placebo-controlled, cross-over study conducted in healthy volunteers showed that tamsulosin 0.8 mg once daily markedly decreased mean ejaculate volume in almost 90% of subjects, with 35% having no ejaculation. By contrast, there was no lack of ejaculation in subjects receiving alfuzosin 10 mg once daily or placebo. Sperm concentrations in urine after ejaculation were similar for the three treatment groups, confirming that the EjD with tamsulosin was unrelated to retrograde ejaculation. It may be related to a peripheral effect on seminal vesicles and/or the vas deferens. A central effect is also plausible, as tamsulosin shows a strong affinity for 5HT1A- and D2-like receptors, both of which are involved in the central command of ejaculation. In conclusion, because treatment options for managing BPH have different effects on sexuality, the sexual dimension should be considered when assessing patients' expectations and the choice of treatment.     

氟西汀治疗早泄的效果观察

目的 :评价氟西汀对早泄的治疗效果及停药后效果维持状况。方法 :将 6 8例早泄患者随机分为A组 :2 4例 ,每天口服氟西汀 2 0mg至研究结束 ;B组 :2 4例 ,每天口服氟西汀 2 0mg至 12周 ,然后改口服安慰剂至研究结束 ;C组 :2 0例 ,每天口服安慰剂至研究结束。分别测定治疗前 4周、治疗后 1周、12周、14～ 16周平均射精潜伏时间。结果 :3组治疗前平均射精潜伏时间差异无统计学意义 (P >0 .0 5 )。A组与B组平均射精潜伏时间经氟西汀治疗前后比较及与C组比较均有明显延长 ,差异有统计学意义 (P <0 .0 1) ;但B组在改服安慰剂后14～ 16周的平均射精潜伏时间与治疗前及对照组相比无统计学意义 (P >0 .0 5 )。结论 :氟西汀能显著延长射精潜伏时间 ,但停药后其疗效并不能维持。     

Towards evidence-based drug treatment research on premature ejaculation: a critical evaluation of methodology

In the last decade, an increasing number of drug studies on premature ejaculation have been published. The methodology used in these studies differed widely. In this review, it is therefore questioned as to how far the differences in methodology could have influenced clinical outcomes. The aim of the present review was to compare the different methodologies that were used in drug studies on premature ejaculation. The majority of these studies were conducted between 1973 and 2003 and were strikingly different in study design and in the quantification of clinical outcomes. It appeared that in some of these studies, placebo and active drug effects were neglected due to an erroneous methodology. The few studies that were using stopwatch assessment at each intercourse at baseline and during treatment and in which the intravaginal ejaculation latency time (IELT) was included appeared to be comparable in their results. The use of a well-defined definition of premature ejaculation, for example, an IELT of less than 1 min revealed reproducible results. Finally, the retrospective use of a questionnaire or a subjective report on ejaculation time induced higher effects with regard to placebo effects and an underestimation of active drug effects. In conclusion, for drug treatment research of premature ejaculation it is recommended to use a randomized double-blind prospective design, the use of the IELT, the use of a stopwatch at each coitus both during a baseline period and during drug treatment and a definition of premature ejaculation as an ejaculation that occurs within 1 min after vaginal penetration.     

SPP、TURP、HoLEP三种前列腺切除术对性功能的影响

目的比较钬激光前列腺切除术（HoLEP）、经尿道前列腺电切术（TURP）和耻骨上前列腺切除术（SPP）三种手术方式对BPH患者性功能的影响。方法随访92例前列腺切除手术的BPH患者，评价：IPSS、性生活情况、勃起功能（阴茎勃起硬度、IIEF-5）和射精情况（射精有无、精液量、有无逆行射精、有无射精痛）。结果（1）三组术后3月IPSS评分均有显著下降（P〈0．01）；（2）三组术后IIEF-5均有不同程度降低，SPP组与术前比较，差异有显著统计学意义（P〈0．01）。校正可能影响IIEF-5的因素后，三组手术IIEF．5评分改变无统计学差异；（3）HoLEP组、TURP组、SPP组勃起功能下降的发生率分别为：38．1％、28．6％、31．0％，HoLEP、SPP组术后勃起硬度下降明显；（4）HoLEP组和SPP组术后逆行射精发生率较术前有显著差异；（5）三种手术对性欲以及射精量的影响均较小；（6）勃起硬度的降低以及逆行射精的发生三种手术间无明显差异。结论HoLEP术后可导致性功能下降，主要表现在勃起功能降低和逆行射精。HoLEP术对性功能的影响与TURP和SPP相似。     

Spinal cord control of ejaculation

Ejaculation is a reflex mediated by a spinal control center, referred to as a spinal ejaculation generator. During intercourse, the spinal ejaculation generator integrates the sensory inputs that are necessary to trigger ejaculation. At the time of ejaculation, it coordinates the sympathetic, parasympathetic, and somatic outflow to induce the two phases of ejaculation, i.e. emission and expulsion. It also provides the brain with signals related to the occurrence of ejaculation. Experimental and clinical data evidenced that these functions were devoted to neurons located in the lumbosacral cord. We recently characterized a population of spinothalamic neurons in the lumbar spinal cord of male rats (LSt cells) that constitutes an integral part of the spinal ejaculation generator. LSt cells send projections to the autonomic nuclei and motoneurons involved in the emission and expulsion phase, and they receive sensory projections from the pelvis. LSt cells are activated with ejaculation, but not following other components of sexual behavior, and lesions of LSt cells completely ablate ejaculatory function. These data support a pivotal role for the LSt cells in the control of ejaculation.     

Prevalence of premature ejaculation and its impact on the quality of life: Results from a sample of Egyptian patients

Premature ejaculation is the most common sexual dysfunction affecting 25%–40% of males of different age groups, imposing psychological and physical burden and causing relationship problems. Because there is no standard definition of PE, there has been the variability in its prevalence data. Aims of this study were to detect the prevalence of premature ejaculation in a sample of Egyptian population and to assess the effect of premature ejaculation on the patients' quality of life and on the sexual function of their partners. Our results revealed that the prevalence of PE was 26.67%. Also, PE‐affected patients and their wives negatively causing dysfunctions in physiological, psychological, cultural and relationship dimensions.     

Central nervous system control of ejaculation

An overview is given of the regions in the spinal cord that are active during ejaculation. Motoneurons involved are the preganglionic sympathetic motoneurons in the upper lumbar spinal cord and the motoneurons in the nucleus of Onuf, located in the upper sacral cord. The first group is involved in the so-called emission phase of ejaculation, the last group in the expulsion phase. Both groups receive afferents from premotor interneurons in the so-called intermediomedial cell groups located at about the same level as the motoneurons themselves. A concept is put forward in which these premotor cell groups represent the central spinal pattern generators for ejaculation, one for the emission phase and one for the expulsion phase. Clinical observations in patients suffering from transection of the spinal cord indicate that the ejaculation motoneurons as well as their spinal central pattern generators are under strong influence of descending pathways originating in supraspinal parts of the brain. The various pathways possibly involved in ejaculation control are reviewed. Finally, the results of the brain activation of a PET-scan study in human males, ejaculating after penile stimulation by their female partner are discussed. Especially the ventral tegmental area and the cerebellum seem to be activated during ejaculation, while the amygdala region is deactivated. Apparently, a general lack of fear is necessary for ejaculation to occur.     

曲唑酮治疗功能性早泄的疗效观察

目的　研究曲唑酮治疗功能性早泄的疗效。方法　对 30例早泄患者给予口服曲唑酮片进行系统治疗并观察 2周及 4周后的疗效。同时与 2 0例口服安慰剂的早泄患者进行对照比较。结果　 2组患者在服药 4周后症状均有不同程度改善 ,曲唑酮治疗组总有效率明显高于对照组 (P <0 .0 5 )。结论　口服曲唑酮是治疗功能性早泄的一种有效安全的方法