Premature ejaculation: a clinical update

Neil R Palmer and Bronwyn G A Stuckey
Med J Aust 2008; 188 (11): 662-666. || doi: 10.5694/j.1326-5377.2008.tb01827.x
Published online: 2 June 2008

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.

Neurobiogenesis of ejaculation

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:

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

Management of the patient

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.

Behavioural techniques

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.

Measures that reduce penile sensation

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:

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

Pharmacological treatments

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

Tricyclic antidepressants

Clomipramine administered daily has been shown to have a greater effect on IELT than daily use of the SSRIs fluoxetine or sertraline, but with a greater side effect profile (P < 0.05).22 A double-blind crossover trial of daily clomipramine treatment (25 mg/day or 50 mg/day) in 15 couples found a significant increase in IELT with both dosing schedules. The baseline pretreatment IELT was 81 seconds, increasing to 202 seconds with 25 mg/day and 419 seconds with 50 mg/day clomipramine (P < 0.01).23 Sexual satisfaction increased for both partners, especially at the higher dose, but this was offset by side effects including dry mouth, constipation, feeling “different”, nausea, sleep disturbances, fatigue, dizziness and hot flushes.

Selective serotonin reuptake inhibitors

Paroxetine and sertraline have been the preferred SSRIs based on the results of clinical trials.24,25 SSRIs block serotonin transporters at the synaptic cleft, resulting in increased serotonin within the central nervous system and spinal cord.2 Serotonin is a potent vasoconstrictor with an inhibitory effect on ejaculation.13 This is not totally a class effect, as there are differences between SSRIs due to gradual desensitisation of 5-HT receptors on the oxytocin-producing neurones.26

However, paroxetine and sertraline have a slow onset of action (5 hours) and long half-lives (1–3 days), making them cumbersome for “on-demand” therapeutic use. Like clomipramine, they need to be taken daily to maintain efficacy in delaying ejaculation. A single-blind placebo-controlled trial using 20 mg paroxetine on-demand 3–4 hours before intercourse showed a significantly delayed IELT compared with placebo. “Priming” by daily dosing with 10 mg paroxetine enhanced this effect.27 Sertraline given as a 50 mg daily dose has also been shown to significantly increase IELT.24

Dapoxetine is the first SSRI developed specifically for PE. It is rapidly absorbed to give peak plasma concentrations within 1–3 hours, has a relatively short half-life of 1.5 hours and a terminal half-life of 18 hours, and can be taken as needed. Studies have confirmed a 50% increase in IELT with 60 mg dapoxetine taken “as needed” compared with placebo.28

Side effects of dapoxetine include headache, nausea, diarrhoea and dizziness. The drug has not been approved by the Federal Drug Administration for marketing in the United States. It has been submitted for approval in Europe and is not yet available in Australia.

Note that careful upward titration of SSRIs from low starting doses is recommended to avoid side effects.

Daily versus on-demand therapy

In a questionnaire-based study involving 88 men who had received no prior treatment, 81% identified a preference for taking an oral therapy daily rather than on demand before intercourse.30 The most frequently reported argument for daily treatment was that this had the least effect on spontaneity of the sexual relationship. McMahon and Touma have demonstrated that daily dosing augments the subsequent response to SSRIs taken on demand.27 However, anejaculation is more common with daily therapy.

Combination therapy

It is possible that using lower doses of SSRIs and clomipramine in combination may reduce side effects and maintain efficacy,31 but no controlled clinical trial of this therapy has been reported. Two studies using SSRIs combined with sildenafil to treat PE have reported benefit of the combination over SSRIs alone.32,33


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.

  • Neil R Palmer1
  • Bronwyn G A Stuckey1,2,3

  • 1 Keogh Institute for Medical Research, Sir Charles Gairdner Hospital, Perth, WA.
  • 2 Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, WA.
  • 3 School of Medicine and Pharmacology, University of Western Australia, Perth, WA.



We would like to thank Mrs Carolyn Bond for help with typing the manuscript and Dr Terry Burgess for assistance with the diagram.

Competing interests:

Bronwyn Stuckey is on a Pfizer advisory board for female sexual dysfunction.

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