Management Practices and Newly Approved Treatments for Premature Ejaculation

Interest in and awareness and recognition of the clinical significance of sexual dysfunction have increased the intensity of research in sexual medicine. This includes improved definition and diagnostic criteria for a number of aspects of both female and male sexual function and dysfunction.^1–5 Meaningful epidemiological as well as interventional studies have been enabled thanks to adequate tools, although several areas remain to be explored.

Premature ejaculation (PE) is a common – if not the most common – sexual dysfunction in males, with a likely prevalence >21%.^6–10 It causes significant concern for both partners in the afflicted relationship. Clinically, PE comprises rapid ejaculation (prior to or within one to two minutes after vaginal penetration) and lack of control, causing sexual as well as general frustration and interpersonal difficulties.² Further classification of PE distinguishes between lifelong (present since start of sexual life and occurring in more than 75% of sexual encounters) and acquired (occurring at some later point in life after an interval of normal sexual function). Still further classification has been proposed taking into account natural variable PE, which occurs in special situations, and premature-like ejaculatory dysfunction, which occurs in men with latency time in the normal range but who complain of PE.^3,11 This introduces other dimensions of PE, suggesting four different subtypes, from very short (lifelong and acquired PE) to normal and long intravaginal ejaculatory latency time (IELT) (natural variable PE and premature-like PE). It also identifies both neurobiological (lifelong) and more psychologically determined subtypes (acquired and prematurelikeejaculatory dysfunction). There may also be a variation in prevalence, with lifelong PE being less common than the prevalentlyoccurring natural variable PE and premature-like ejaculatory sexual dysfunction.^12,13 The initiative taken by the International Society for Sexual Medicine (ISSM) to formulate an evidence-based definition of PE seems to be the most comprehensive operational definition and is the current benchmark.² The consequences of PE include embarrassment, loss of self-esteem, anxiety and a feeling of inferiority as a result of being unable to respond to a partner’s expectations and the partner having similar negative experiences.¹⁴

There is no recognised organic disease associated with PE, and the aetiology or aetiologies remain to be elucidated.¹⁵ A variety of hypotheses have been suggested, including central mechanisms with a dysregulation of serotonin (5-HT) activity (5-HT 1A receptor desensitisation, 5-HT 1B hyperactivity, change in 5-HT-transporter activity) in central nervous system (CNS) structures of importance for regulation of the ejaculatory reflex control, hypersensitivity of the glans penis and primary as well as secondary psychological mechanisms.¹⁶ Ejaculation involves two processes: emission (emptying of accessory sex glands into the urethra) and expulsion of semen through the urethra caused by contraction of mainly ischiocavernous and bulbocavernous muscles. These processes are highly co-ordinated and follow a certain sequence, and also involve closing of the internal bladder sphincter to prevent emptying of semen into the bladder.^17,18 The neural control of ejaculation involves specific centres in the supra-spinal and spinal region, as well as peripheral neuronal networks. Centres in the spinal cord – the spinal ejaculation generator – are supposed to co-ordinate peripheral and supra-spinal input and activation of sympathetic, parasympathetic and somatic efferent signals to structures directly executing the ejaculatory process.¹⁹ The spinal centre is under inhibitory and excitatory influence by supra-spinal sites.²⁰ The complexity of the ejaculatory reflex thus offers several targets for interference and therapeutic possibilities, but also complicated interactions with other central and peripheral functions.

2009 is a landmark in the development of drug therapies for the treatment of PE, as the first approval was achieved in Europe for a drug developed for the treatment of PE: dapoxetine, marketed under the brand name PRILIGY^®.