Premature ejaculation Definition of premature ejaculation The stimulation of the 5-HT2C receptor with 5-HT2C agonists results in a delay of ejaculation in male rats, whereas the stimulation of postsynaptic 5-HT1A receptors results in shortening of ejaculation latency 4, leading to the hypothesis that men with PE may have hyposensitivity of 5-HT2C and/or hypersensitivity of the 5-HT1A receptor 5,6. Recently, multiple serotonin (5-HT) receptors have been characterized, for example 5-HT1a, 5-HT1b, 5-HT2a, 5-HT2b, etc. Serotonergic neurons are widely distributed in the brain and the spinal cord and are predominantly found in the brainstem, raphe nuclei, and the reticular formation.

Whereas dopamine promotes seminal emission/ejaculation through D2 receptors, serotonin is inhibitory. Of the many studies that have been carried out to examine the role of the brain in the development and mediation of sexual functioning, dopamine and serotonin have emerged as essential neurochemical factors. Many neurotransmitters are involved in the control of ejaculation, including dopamine, norepinephrine, serotonin, acetylcholine, oxytocin, GABA, and nitric oxide 2. Orgasm is the result of cerebral processing of pudendal nerve sensory stimuli resulting from increased pressure in the posterior urethra, sensory stimuli arising from the verumontanum, and contraction of the urethral bulb and accessory sexual organs. Intermittent contraction of the urethral sphincter prevents retrograde flow into the proximal urethra 1. The bladder neck closes to prevent retrograde flow the bulbocavernosus, bulbospongiosus, and other pelvic floor muscles contract rhythmically and the external urinary sphincter relaxes.

Ejection also involves a sympathetic spinal cord reflex upon which there is limited voluntary control. Ejection is mediated by somatic nerves (S2–S4), and involves pulsatile contractions of the bulbocavernosus and pelvic floor muscles together with relaxation of the external urinary sphincter. Emission consists of contractions of seminal vesicles and the prostate, with the expulsion of sperm and seminal fluid into the posterior urethra, and is mediated by sympathetic nerves (T10–L2). On the basis of functional, central, and peripheral mediation, the ejaculatory process is typically subdivided into three phases: emission, ejection (or penile expulsion), and orgasm. Neurochemically, this reflex involves a complex interplay between central serotonergic and dopaminergic neurons, with the secondary involvement of cholinergic, adrenergic, oxytocinergic, and γ-aminobutyric acid (GABA) neurons. The ejaculatory reflex comprises sensory receptors and areas, afferent pathways, cerebral sensory areas, cerebral motor centers, spinal motor centers, and efferent pathways. The anatomy and physiology of the ejaculatory response The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE), through delayed ejaculation to a complete inability to ejaculate (known as anejaculation), and includes retrograde ejaculation. Additional research is required to gain further understanding of the disorders of ejaculation and orgasm.Įjaculatory dysfunction is one of the most common male sexual disorders.

Graded behavioral therapy is indicated when psychogenic or relationship factors are present, and is often best combined with PE pharmacotherapy in an integrated treatment program. All men seeking treatment for PE should receive basic psychosexual education. The management of acquired PE is etiology specific and may include PE pharmacotherapy and/or erectile dysfunction pharmacotherapy in men with comorbid erectile dysfunction. Lifelong PE is best managed with PE pharmacotherapy (selective serotonin reuptake inhibitors and/or topical anesthetics). PE management is largely dependent on the etiology.

This search was then cross-referenced manually for all papers. MEDLINE, Web of Science, PICA, and EMBASE and the proceedings of major international and regional scientific meetings during the period 1980–2012 were searched for publications or abstracts using the word premature ejaculation in the title, abstract, or keywords. The objective of this work was to review evidence supporting the efficacy and safety of treatments of PE. Development and regulatory approval of new drugs specifically for the treatment of PE will reduce the reliance on off-label treatments and serve to fill an unmet treatment need. Several other drugs have limited or no empirical basis as a treatment for PE. Pharmacotherapy of PE with dapoxetine, off-label antidepressant selective serotonin reuptake inhibitor, and topical anesthetic drugs is common, effective, and safe. Premature ejaculation (PE) is a common male sexual disorder that is associated with major personal and interpersonal negative psychological consequences.

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