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Abstract
Premature ejaculation (PE) is the most prevalent male sexual complaint, yet it remains underdiagnosed and undertreated. The sympathetic, parasympathetic, and somatic spinal centers, under the influence of sensory genital and cerebral stimuli integrated and processed at the spinal cord level, act in synergy to command physiologic events occurring during ejaculation. Experimental evidence indicates that serotonin (5-HT), throughout brain descending pathways, exerts an inhibitory role on ejaculation and pharmacologic manipulation of the serotonergic system has been performed in rats, with the antidepressant selective serotonin reuptake inhibitors (SSRIs) exhibiting the greatest efficacy in delaying ejaculation. Over the last decade, an increasing number of studies of drug treatment of PE have been published. A meta-analysis of those studies demonstrated similar efficacies for daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline and fluoxetine, with paroxetine (hydrochloride) hemihydrate exerting the strongest effect on ejaculation. On the basis of fundamental insights into serotonergic neurotransmission, it has been suggested that on-demand selective serotonin reuptake inhibitor (SSRI) treatment will not lead to similarly impressive delays in ejaculation as has been observed with daily SSRI treatment. Apart from daily treatment with SSRIs, PE can be delayed by on-demand use of topical anaesthetics. Treatment with phosphodiesterase type 5 inhibitors may be used if PE is accompanied by erectile difficulties.
Figures and Tables
Fig. 1
Schematic representation of the control of the seminal tract and the bulbospongiosus (BS) muscle by the spinal ejaculation generator (LSt cells) in rats. The spinal ejaculation generator projects to the parasympathetic sacral parasympathetic nucleus (SPN) and sympathetic dorsal grey commissure (DGC) and intermediolateral cell column (IML) preganglionic neurons, and BS muscle motoneurones (Onuf's nucleus). The parasympathetic centre projects to the seminal tract via the pelvic nerve (PN) and the major pelvic ganglion (MPG). The sympathetic centre innervates the seminal tract by sending projections through the lumbar sympathetic chain (LSC) to the superior hypogastric plexus (SHP) and then via the hypogastric nerve (HN), which joins the MPG. The motoneurones of the BS muscle project to the muscle through the motor branch of the pudendal nerve (PudN).13
Fig. 2
Diagram of brain structures and putative central pathways involved in ejaculation. Structures containing serotonin auto/heteroreceptors are indicated in grey. BNSTpm: posteromedial bed nucleus of stria terminalis, MeApd: posterodorsal medial amygdaloid nucleus, MPOA: medial preoptic area, PAG: periaqueductal grey, nPGi: paragigantocellular nucleus, PNpd: posterodorsal preoptic nucleus, PVN: paraventricular thalamic nucleus, SPFp: parvicellular part of the subparafascicular thalamus.13
Table 3
Different classes of drugs for the on-demand treatment of premature ejaculation
PDE-5: phosphodiesterase type 5, SSRI: selective serotonin reuptake inhibitor, TCA: tricyclic antidepressant, Tmax: time to maximum concentration, + indicates weak, + + indicates moderate, + + + indicates strong, ? indicates may have moderate effect, but not very clear due to lack of controlled studies
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