Premature ejaculation: a clinical update

Since the late 1990s, when phosphodiesterase type 5 (PDE5) inhibitors became available for the treatment of erectile dysfunction (ED), men have been more forthcoming in acknowledging and discussing their impotence. However, they are still somewhat reticent about acknowledging the problem of premature ejaculation (PE), despite the fact that it is the most common male sexual complaint and can be managed with a success rate similar to that for ED (about 75%). As with ED, what was originally thought to be a purely psychological disorder is now recognised to have an organic basis.

PE, as defined by the Diagnostic and statistical manual of mental disorders (DSM-IV-TR), is ejaculation occurring, without control, on or shortly after penetration and before the person wishes it, causing marked distress or interpersonal difficulty.1 Although timing of intravaginal ejaculatory latency time (IELT) (ie, time from penetration to ejaculation) is not included in this definition, an IELT of less than 2 minutes, or ejaculation occurring before penetration, has been considered consistent with PE.2 Recently, the International Society for Sexual Medicine has redefined PE, to include IELT, as:

The core elements for the diagnosis of PE are the time to ejaculation (verified objectively by use of a stopwatch by the man or his partner), the inability to delay ejaculation, and the existence of negative consequences of PE.

True PE may be primary (lifelong), occurring and persisting from the first sexual encounter, or secondary (acquired), occurring after a period of normal control of ejaculatory function. Two further classifications are proposed but not widely accepted: normal variable PE, in which early ejaculation occurs inconsistently and is situational; and premature-like ejaculation, in which there is a subjective perception of PE although the IELT is normal (ie, > 2 minutes).4

Reference to the frustration caused by PE can be traced back to the Kama Sutra, written between the 1st and 4th centuries ce.5 It consistently affects about one in three men, although two in three men may be affected at some time in their lives.6 It is suspected that primary PE has a genetic basis. In one study, 91% of men with primary PE had a first-degree relative with PE.7 The Hite report, which surveyed more than 7000 men in the United States, found that 70% of males responded positively to the question “Do you ever orgasm ‘too soon’ after penetration?”; 21% reported that they ejaculated within 50–60 seconds of vaginal penetration and 62% ejaculated within 1–5 minutes.8 Masters and Johnson stated that a man has PE if he ejaculates before his partner achieves orgasm in more than 50% of sexual encounters.9 But this definition is problematic, as it is couched in terms of the partner’s sexual function and/or expectations. A study of 500 couples objectively measuring IELT revealed a highly skewed distribution with a median IELT of 5.4 minutes (range, 0.55–44.1 minutes).10

Repeated PE, particularly when the man is criticised, actively or passively, by his partner, may lead to loss of self-esteem, anxiety, ED and reduced libido. It may also lead to sexual difficulties for the partner due to lack of adequate foreplay, and may contribute to anorgasmia. The presence of PE in the man may be revealed when his partner presents with sexual dysfunction.

The neurobiogenesis of ejaculation is represented in Box 1. Stimulation of the glans penis mucosal sensory receptors (Krause finger corpuscles) is relayed by the pudendal nerve afferent fibres to S4, and then to the hypogastric plexus at the T10–L2 sympathetic ganglia. Sensory information is relayed centrally to the brain, where three ejaculatory centres are situated. Two are in the hypothalamus (the medial preoptic area and the paraventricular nucleus) and one is in the midbrain (the periaqueductal grey).

These centres integrate the peripheral events of seminal emission, ejaculation and orgasm. The efferent dopamine output by these centres is modulated by the nucleus paragigantocellularis. This has an inhibitory influence, from its serotonergic neurones centrally and to the lumbar–sacral motor nuclei, which tonically inhibits ejaculation.11 Neurotransmitters involved in these centres include noradrenaline, γ-aminobutyric acid, oxytocin, nitric oxide, serotonin and oestrogen.

Ejaculation is triggered by efferent dopamine acting on the D2 receptors of central and spinal efferent fibres, which relay information down to the sympathetic ganglia at T10–L2 and sacral fibres.12 This stimulates pudendal nerve fibres from the S2–S4 region of the spinal cord, resulting in:

• Smooth muscle contractions of the prostate, seminal vesicles, vas deferens and epididymis. This increases semen volume and fluid content, which is forced into the posterior urethra under the control of the sympathetic nervous system, producing emission (Stage I).

• Rhythmic contractions of the pelvic floor and bulbo- and ischiocavernosus muscles, controlled by parasympathetic nerves, which override sympathetic nerves. This propels seminal fluid out through the urethra, with resultant ejaculation (Stage II).

• Orgasm (Stage III).

Primary PE is thought to be due to hyposensitivity of 5-hydroxytryptamine 2c (5-HT2c) serotonin receptors or hypersensitivity of 5-HT1 serotonin receptors, causing lowering of the ejaculatory threshold and shortened IELT.11,13

Control over ejaculation and satisfaction with sexual intercourse are the central issues for men with PE.14 Keep these two outcomes in mind when assessing PE and evaluating treatment for this condition.

Active treatment of PE probably started over 50 years ago with Semans’ “stop-start” technique for prolonging the neuromuscular reflex responsible for ejaculation.16 The man informs his partner to stop genital stimulation until the subjective sensation of high arousal disappears. Stimulation is reintroduced and the cycle is repeated if necessary. One weakness in Semans’ study was the lack of a control group. Further behavioural studies by Wolpe and Lazarus17 and Masters and Johnson’s “squeeze technique”9 were not able to demonstrate that these behavioural techniques definitely “cured” PE. Such techniques are considered by many to be unhelpful in resolving relationship issues. Generally they are intrusive, mechanical and may fracture a normal love/lust act, relationship and spontaneity.

Condoms reduce glans penis sensitivity and have been used in the treatment of PE. Topical preparations have also been used to reduce glans penis sensitivity. These include:

• Lignocaine–prilocaine aerosol (topical eutectic mixture for premature ejaculation [TEMPE]) applied 20–30 minutes before sexual intercourse and removed before contact with the partner. Trials of this treatment in the United Kingdom and The Netherlands have shown statistically and clinically significant prolongation of IELT compared with placebo.18

• Lignocaine–prilocaine cream (eutectic mixture of local anaesthetic agents [EMLA]) applied thinly to the glans and distal shaft and covered by a condom for 10–20 minutes. If the condom is removed for intercourse, residual cream should be washed off. In a randomised placebo-controlled study of this treatment, IELT improved significantly above baseline.19

• Lignocaine spray (Stud 100) applied to the glans in 3–6 sprays, 5–15 minutes before sexual intercourse. Although this treatment has been available for 25 years, there have been no randomised controlled studies of its efficacy.

• Severance Secret (SS) cream. This is available only in Asia and consists of herbal extracts. Efficacy over placebo has been shown in controlled studies.

The most prominent side effect of anaesthetic agents is penile numbness, which may in turn lead to loss of the erection. Adverse effects of SS cream are local symptoms of irritation and burning and delayed ejaculation.20

It is more common for psychological problems to be secondary to PE rather than the cause. Counselling may be useful in conjunction with other treatments if it is considered to be helpful in improving self-esteem, but is not effective in treating the cause of lifelong PE.

Certain antidepressants — the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline — have been shown to increase IELT, such that the patient perceives greater control over ejaculation (see Box 3 for recommended doses of pharmacological agents). Other agents, such as nefazodone, citalopram and fluvoxamine, have been found to be ineffective.21

The approach to treating secondary or acquired PE is to treat the underlying condition. The most common cause of secondary PE is declining erectile function, where rapid ejaculation becomes a compensatory mechanism, either conscious or unconscious, for the inability to maintain the erection. An alternative explanation is that lower levels of nitric oxide and increased sympathetic tone, associated with ageing, both predispose to erectile failure and hasten ejaculation. PDE5 inhibitors may be effective in treating ED but do not prevent detumescence once ejaculation has occurred. By contrast, alprostadil intracavernosal injections prolong an erection beyond the point of ejaculation. However, they are not recommended for treating primary PE without coexistent ED, largely because of the lack of evidence for their use, but also because of the risk of priapism (especially in men without vascular compromise) and the risk of penile fibrosis with long-term use.4,34,35

PE is a common problem, and primary (lifelong) PE is thought to have a biological basis. Assessment and management of PE necessarily involves both the patient and his partner. The primary aims of therapy are for the man to regain a sense of control over his ejaculation and for the man and his partner to feel satisfaction with sexual intercourse.

The most effective and well tolerated treatment for PE is pharmacological therapy with certain SSRIs, usually given in small doses on a daily basis. Newer analogues of SSRIs are in development for the treatment of PE.

1 Neurobiogenesis of ejaculation

nPGi = nucleus paragigantocellularis.