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ESSM Science

Section Editor:
Asif Muneer
Clinical Fellow in Urology
Insitute of Urology
UCLH
London
e-mail: asif.muneer@uclh.nhs.uk

Premature Ejaculation: Unravelling the pathophysiology



Amr Abdel Raheem
Clinical Fellow in Andrology, Institute of Urology, London, UK
Asif Muneer. Science Editor

Premature ejaculation (PE) is a common male sexual dysfunction affecting 5-40% of sexually active men. Definitions for PE have been subjective and lack standardisation. This led to a more recent and objective definition of premature ejaculation which depends upon the intra-vaginal ejaculation latency time (IVELT). However sev¬eral cut-off points ranging from 1 to 7 minutes have been suggested by dif¬ferent studies. A recent study based on normative data suggested a cut off point of 60 seconds for definite PE and 60-90 seconds for probable PE. Understanding the physiology of ejaculation is essential in order develop targeted therapies for premature ejaculation. We present an overview of the theories of premature ejaculation.

Phases of ejaculation

(i) Emission::
During this phase there is sequential contraction of the epididymi, vasa, seminal vesicles and prostate to propel the semen in the posterior urethra and closure of the bladder neck to prevent reflux in the bladder.

Afferent: pudendal nerve (S2,3,4)
Efferent: sympathetic fifibres (T10-L2) -> inferior mesenteric ganglion -> hypogastric nerve.

This phase can be voluntary controlled and is influenced by inhibitory and facilitatory cortical centres.

(ii) Ejaculation Proper:
This is the expulsion of semen from the posterior urethra to the outside. It occurs due to rhythmic contraction of the pelvic floor and perineal muscles (Pudendal nerve S2, 3, 4). It is an involuntary spinal somatic reflex in response to the emission phase. It is inevitable once emission occurs.

(iii) Orgasm
A cerebral event of intense pleasure occurring with ejaculation proper.

Cerebral control of ejaculation

The medial preoptic area (MPOA) and the paraventricular nucleus (PVN) of the anterior hypothalamus control ejaculation. Dopamine and serotonin are the main neurotransmitters involved in ejaculation. Dopamine stimulates ejaculation mainly by acting on D2 receptors while serotonin (5-HT) inhibits ejaculation although it has been suggested that different serotonergic receptor subtypes may have opposing effects on sexual function. Activation of
5-HT1A receptors is facilitatory while activation of 5-HT2C receptors is inhibitory.

Theories of premature ejaculation

Premature ejaculation can be lifelong (primary) or acquired (secondary).

Psychogenic theories

Several theories tried to explain PE based on psychogenic factors. Many authors suggested that anxiety during intercourse leads to activation of the sympathetic system thus causing PE. Other authors postulated that anxiety distracts the man from monitoring his excitability thus preventing him from controlling the ejaculatory reflex. Anxiety during sex may be caused by fear of failure (performance anxiety), interpersonal issues, phobia of STDs and unsuitable environment.

Masters and Johnson suggested that PE is caused by habituation and conditioning through early sexual experiences that are often associated with anxiety and rush. On the other hand some authors suggested that men with PE failed to learn ejaculatory control techniques during their early sexual experiences. According to this theory men with normal ejaculation have consciously learnt ejaculatory control techniques such as thought distraction, pelvic muscle contraction and alternation of the pattern of thrusting in their early sexual experiences and continued to use them unconsciously later on.

Kaplan proposed that men with PE fail to recognize their level of sexual excitation and thus they are unaware that they are about to ejaculate which makes them unable to control ejaculation.

It has also been suggested that low frequency of intercourse may predispose to PE. Frequent intercourse leads to higher ejaculatory threshold, decreased performance anxiety and better control of the ejaculatory reflex by recognising excitability levels that precede ejaculation. However other authors reported that the low frequency of intercourse observed in some men with PE is a consequence rather than a cause and represents avoidance for fear of not satisfying the partner.

Older theories include the psychoanalytic theory which postulates that PE represents unconscious hostility towards the female by soiling her and preventing her from achieving sexual pleasure and the psychosomatic theory which postulates that PE may represent a psychosomatic disorder.

Organic causes for PE

Penile hypersensitivity has been postulated to be the cause of PE. Here men with PE reach the ejaculatory threshold more rapidly or have a lower threshold for ejaculation compared to normal men. This was explained by better innervation of the penis and greater cortical representation of the penile sensory nerves whereas other groups have suggested that PE is caused by a faster emission phase which is caused by a hypersensitive bulbocavernosal reflex. A genetic basis for PE has also been reported based on studies that observed that the incidence of PE in first degree relatives of men with PE is greater than the incidence of PE in the general population.
More recent studies focus on the role of central neurotransmitters in the pathophysiology of PE. Waldinger (1998) postulated that lifelong PE may be explained by abnormal serotonin receptor function due to genetic factors. This abnormality is either in the form of hyposensitivity of the 5-HT2C receptors which are inhibitory and/or hypersensitivity of the 5-HT1A receptors which are facilitatory which makes those men have a genetically set low threshold for ejaculation. Thus treatment with a selective serotonin reuptake inhibitor (SSRI) will raise the serotonin level to stimulate the 5-HT2C receptors to adjust the ejaculatory threshold and delay ejaculation. The extent of the SSRI induced delay will depend on the genetically determined ejaculatory threshold set point.

Acquired premature ejaculation

PE may occur secondary to erectile dysfunction (ED) as patients with ED tend to be in a hurry to complete intercourse and ejaculate before losing their erection. Men with ED also tend to have performance anxiety which may be a contributing factor towards PE. PE was also noted to be more frequent in patients with prostate disorders as in chronic prostatitis which may be caused by irritation of the pelvic nerves thus lowering the threshold of neural discharge. PE has also been noted to be more frequent in men with thyroid disorders in particular hyperthyroidism. PE may also occur in CNS lesions involving the centres that control ejaculation.
The pathophysiology of premature ejaculation is undoubtedly multifactorial although the identification of neurotransmitter imbalances has led to targeted therapies. Despite the use of pharmacotherapies, the condition can still be problematic indicating that several unknown neurotransmitters are involved. Further studies are needed to completely understand the neurobiologic and genetic basis of premature ejaculation in order to develop more efficacious therapies.