Clinical Review: Premature ejaculation

Premature ejaculation (PE) is one of the most common conditions reported by men in various health surveys across the globe.1

Section 1 Epidemiology and aetiology

Despite PE's association with personal distress and frictions in relationships, it has also been found that men with the condition do not necessarily discuss it with their GP.

Classification
PE can be subdivided into two categories: lifelong (LPE) and acquired (APE). LPE is attributed to onset from the first sexual experience, whereas acquired PE is characterised by gradual or sudden onset during the passage of time. According to the International Society for Sexual Medicine (ISSM)definition, PE is a male sexual dysfunction characterised by:

  • Ejaculation always or nearly always before or within about one minute of vaginal penetration, from the first sexual experience (LPE), or a clinically significant reduction in latency time, often to about three minutes or less (APE)
  • Inability to delay ejaculation on all or nearly all vaginal penetrations
  • Negative personal consequences, such as distress, frustration, and/or avoidance of sexual intimacy.

Two further subtypes are natural variable PE, characterised by irregular early ejaculation, and premature-like ejaculatory dysfunction, which is more of a subjective perception of early ejaculation, where the latency time is in the normal range.

Awareness of these subtypes and variations aids patient stratification, diagnosis and management.

Epidemiology
Although the history of PE dates back more than a century,2 it is difficult to assess its exact prevalence because of changing definitions and problems with interpreting the data from various studies.

The National Health and Social Life Survey suggested a prevalence of about 31% in the US, while a British survey estimated it at 14% to 31%.3

The Global Study of Sexual Attitudes and Behaviors survey was conducted in 29 countries in men aged 40 to 80 years and estimated worldwide prevalence at about 30%.

Most men with PE do not seek medical advice, so there is a significant difference between prevalence rates in the general population and patients presenting to their GP.

All current studies suggest further research is needed in this field.

Pathophysiology
The aetiology of PE is unknown, although various hypotheses have been proposed. In the past, it was thought to have a psychological basis, largely due to anxiety-related problems. More recently, other aetiologies have been elucidated using neurobiology, genetics and other factors.

Serotonin has been by far the most studied neurotransmitter in various models for understanding the basis of PE.

It is postulated that PE might be caused by hyposensitivity of the 5-HT2C or hypersensitivity of the 5HT1A receptors.

Dopamine and oxytocin have also been studied in animal models and seem to have a stimulatory effect on ejaculation.4,5

There is scant data on genetic studies for PE. However, there are suggestions that numerous genetic variants, rather than individual genetic polymorphism, might cause it.

Other factors include obesity, poor overall health, prostatitis, thyroid disorders and stress. Traumatic sexual experiences are also risk factors associated with PE.

Section 2 Making the diagnosis

It is vital to assess each case in detail and some studies have suggested involving the patient's partner if they are willing to do so. It is well established that PE has serious consequences for the patient's and their partner's psychological and physical heath, interpersonal difficulty and overall reduction in quality of life.

It is not uncommon for patients to shy away from this topic, so the GP should always investigate with tact and diplomacy. Once a level of confidence is achieved during the consultation, patients feel less embarrassed to talk about the problem.

The ISSM recommends taking a full medical and psychological history (see box 1). As in patients with erectile dysfunction, European Association of Urology (EAU) guidelines recommend a focused physical examination, especially in APE.

The aim is to identify risk factors, such as chronic illness, endocrinopathy, autoimmune neuropathy, Peyronie's disease and prostatitis. Laboratory tests are only indicated if the physical examination and/or history suggest an organic cause.

Box 1: Key questions to ask while taking a history of PE, as recommended by ISSM

Diagnosis (recommended)

  • What is the time between penetration and ejaculation?
  • Can you delay it?
  • Do you feel annoyed or frustrated by PE?

LPE or APE (optional)

  • When did you first experience PE?
  • Have you experienced PE since your first sexual experience on every/almost every attempt with every partner?

Erectile dysfunction (optional)

  • Is your erection strong enough to achieve penetration?
  • Do you have difficulty maintaining erection until you ejaculate during intercourse?
  • Do you ever rush intercourse to prevent loss of your erection?

Impact on relationships (optional)

  • How upset is your partner with your PE?
  • Does your partner avoid intercourse?
  • Is PE affecting your overall relationship with your partner?

Previous treatment (optional)

  • Have you received PE treatment before?

Impact on quality of life (optional)

  • Do you avoid sexual intercourse because of embarrassment?
  • Do you feel anxious, depressed or embarrassed because of your PE?

Section 3 Managing the condition

It is important to explore patients' expectations before initiating treatment. If there are any obvious causes, for example, co-existing erectile dysfunction or infections, these should be addressed first.

Behavioural therapy
In lifelong PE, behavioural therapy may not be of great help, but in APE, it may help those who do not want to use pharmacological therapy.

Psychotherapy can help patients to relieve their anxiety, gain confidence and develop sexual skills, and may also address other relationship and interpersonal problems that have arisen in the course of condition.

Two behavioural therapies6 are listed in box 2.

Box 2: Behavioural therapies
  • In the stop-start technique, the partner stimulates the penis until the patient feels the urge to ejaculate, then stops the stimulus to let the urge pass, after which stimulation is started again.
  • In the squeeze technique, the partner applies manual pressure to the glans of the penis just before ejaculation, until the patient loses the urge.

Overall success rates of 50% to 60% are reported in the literature, although there is a lack of controlled research to support this further.

Pharmacological therapy
Pharmacological therapy ranges from the application of topical preparations to oral therapy and has a variable profile.

Local anaesthetic applied to the glans is the oldest form of therapy for PE. Lidocaine and prilocaine, in the form of cream or spray, can be used up to 20-30 minutes before intercourse. Various studies have shown intravaginal ejaculatory latency time (IELT) improving from 1.4 to 8.45 minutes when compared with placebo.

However, their disadvantages include glans hypoanaesthesia, vaginal numbness, possible transvaginal absorption and female anorgasmia unless a condom is used.

EAU guidelines also mention SS-Cream, which needs to be applied to the glans an hour before intercourse and washed off immediately before coitus. Up to 82% improved satisfaction was seen in the group using this compared with placebo.

SSRIs have been used to treat PE off-label. Long-term administration will increase the synaptic levels of serotonin and desensitises 5HT1A and 5-HT1B receptors, delaying ejaculation.

A systemic meta-analysis has shown SSRIs were expected to raise mean IELT 2.6-fold to 13.2-fold. However, they need to be taken for two weeks before the effects are evident. It also found paroxetine to be superior to fluoxetine, clomipramine and sertraline. Common side-effects include fatigue, nausea, diarrhoea and vomiting.

Dapoxetine has emerged more recently as an on-demand, short-acting SSRI treatment for PE.7 It has received approval in more than 50 countries for the treatment of PE.

In RCTs dapoxetine 30mg or 60mg taken one to two hours before sexual intercourse increased IELT 2.5-fold to threefold compared with placebo. It has a shorter half-life and less than 5% of peak concentration levels remain in the body after 24 hours. Fewer side-effects were reported compared with traditional SSRIs. No drug interactions have been found between dapoxetine and phosphodiesterase (PDE5) inhibitors.

PDE5 inhibitors have been used in the treatment of erectile dysfunction and coexisting PE with or without SSRIs, but there is no evidence to support their use in LPE with normal erectile function.

Pharmacological agents such as tramadol, alfuzosin and terazosin may have some benefit in PE, but more research is needed in this field.

Section 4 Prognosis

It is difficult to predict the prognosis of PE owing to the lack of availability of follow-up data. Once the underlying aetiology is addressed, good outcomes are usually achieved.

Patients with coexisting erectile dysfunction report better outcomes with the use of PDE5 inhibitors. Some may only need psychosexual and behavioural therapy.

GPs play a vital part in the follow-up of these patients. It is important to address problems of PE, which can lead to relationship breakdown. Regular follow-up of these patients will also provide valuable data on the efficacy of any given treatment.

Section 5 Case study

A 49-year-old man presented to his GP for a routine check-up. His past medical history includes some stress-related problems. He has smoked 20 cigarettes daily for the past 20 years. He was off work because of stress for six months but has now returned to work. He is divorced but has recently started a new relationship.

On close questioning, he mentions that since he has been in his new relationship, he is finding it difficult to have successful intercourse. He is getting good erections but is ejaculating either just prior to penetration or within one minute of penetration. He is getting very worried about his condition and thinks that this is going to have serious impact on his relationship.

His physical examination is unremarkable with normal external genitalia and normal prostate examination. His urine and routine blood tests are within normal range as well.

As during the consultation a trusted relationship is built between patient and doctor, it made it easy to make further recommendations. He seemed to have his problem rooted in anxiety and stress. He was referred to a psychosexual therapist. He returned after four months and reported marked improvement.

Section 6 Evidence base

Clinical trials

  •  Li J, Yuan H, Bai Y et al. Dapoxetine for premature ejaculation: an updated meta-analysis of randomized controlled trials. Clin Ther 2014; 12: 2003-14.
  • Giuliano F, Patrick DL, Porst H et al. Premature ejaculation: results from a five-country European observational study. Eur Urol 2008; 53: 1048-57.
  • McCarty EJ, Dinsmore WW. Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation. Core Evidence 2012; 7: 1-14.

Guidelines

  • European Association of Urology. Guidelines on male sexual dysfunction; updated 2014 (EAU Guidelines).
  • Althof SE, Abdo CH, Dean J et al. International Society for Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation. J Sex Med 2010; 7: 2947-69.

Key text

  • Wein AJ, Kavoussi LR, Novick AC et al. Campbell-Walsh Urology (10th edition). St Louis, WB Saunders, 2011 (chapter 26).

Click here to take a test on this article and claim a certificate on MIMS Learning

  • Contributed by Mr Paul Anderson, consultant urological surgeon/genito-urethral reconstructive surgeon, Dudley Group of Hospitals NHS Foundation Trust and honorary consultant urological surgeon, Royal Centre for Defence Medicine, University Hospitals Birmingham NHS Foundation Trust, and Mr Zubair Cheema, urology ST, West Midlands Deanery.

References
1. Rosenberg MT, Sadovsky R. Identification and diagnosis of premature ejaculation. Int J Clin Pract 2007; 61(6): 903-8.
2. Gross S. Practical treatise on impotence and sterility and allied disorders of the male sexual organs. Edinburgh, YJ Pentland, 1887.
3. Hatzimouratidis K, Amar E, Eardley I et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010; 57: 804-14.
4. Clement P, Bernabe J, Compagnie S et al. Inhibition of ejaculation by the non-peptide oxytocin receptor antagonist GSK557296: A multi-level site of action. Br J Pharmacol 2013; 169: 1477-85.
5. Clement P, Pozzato C, Heidbreder C et al. Delay of ejaculation induced by SB-277011, a selective dopamine D3 receptor antagonist, in the rat. J Sex Med 2009; 6: 980-8.
6. Semans JH. Premature ejaculation: a new approach. South Med J 1956; 49(4): 353-8.
7. McCarty EJ, Dinsmore WW. Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation. Core Evidence 2012; 7: 1-14.

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Organise an audit of patients in your practice who have PE and review their access to CBT.
  • Review NICE and EAU guidelines for updates on the management of patients with PE.
  • Arrange a meeting with the consultant urological surgeon to discuss a protocol for referring patients with PE.

Save this article and add notes with your free online CPD organiser and take tests and claim certificates for CPD at mimslearning.co.uk

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