New Insights in Premature Ejaculation

Ejaculatio praecox, or premature (rapid, early) ejaculation (PE), is a prevalent male sexual complaint. It may be part of the normal ejaculation variability in men, but it may also be the symptom of an ejaculatory dysfunction.

Recently, it was shown that DSM-IV-TR definition of PE has a low positive predictive value, indicating a high risk of false-positive diagnoses.¹ For example, because of the absence of an evidence-based cutoff point of the ejaculation time, DSM allows the clinician to diagnose PE in men who actually ejaculate in 10 to 20 minutes, which obviously is not a rapid ejaculation. This inaccuracy hampers clinical, epidemiological, and drug treatment research. In the past decade, various developments paved the way for a better definition of PE. In 1994, in a report by Waldinger and colleagues,² the term "intravaginal ejaculation latency time" (IELT) was introduced and defined as the time between vaginal penetration and intravaginal ejaculation. For research purposes, the preferable method for assessing IELT is with the use of a stopwatch during coitus.

Complaint vs disorder

It is important to distinguish PE as a "complaint" versus PE as a "syndrome."³ The high prevalence (20% to 30%) of PE that has been repeatedly found in epidemiological studies⁴ might be a consequence of the fact that many men occasionally, or more frequently, experience a rapid ejaculation. In other words, the high prevalence of PE only indicates a high prevalence of PE complaints. It does not mean that all these men have an ejaculatory "disorder."

PE as a disorder is characterized by a specific cluster of symptoms, ie, a syndrome. For example, men with the syndrome of lifelong PE usually report a cluster of symptoms. They not only report the experience of rapid ejaculations but also report that these rapid ejaculations have occurred since their first sexual encounters, that they occur in more than 90% of their sexual intercourse experiences, that they happen with nearly every female partner, and that the ejaculation mostly occurs within 30 to 60 seconds after penetra- tion. Although a biological marker for this syndrome has not yet been found, there are indications from both animal and clinical research that lifelong PE is a (mainly) neurobiological dysfunction, with secondary psychological consequences.

This syndrome should be distinguished from complaints of men who have rapid ejaculations with no other associated well-known symptoms that are based on underlying pathology. For example, when a man reports "sometimes" experiencing rapid ejaculation, his rapid ejaculation is probably only the manifestation of normal variability of ejaculatory performance.

Proposal for DSM-V classification

About 20 years ago, PE was classified into "lifelong PE " and "acquired PE."⁵ Recently, a new classification of PE was proposed based on controlled clinical and epidemiological stopwatch studies,^3,6 and it included 2 other PE syndromes: "natural variable PE" and "premature-like ejaculatory dysfunction."

Men with lifelong PE experience rapid ejaculations from their first sexual encounters with nearly every female partner; and the IELT is consistently very short, ie, less than 1 to 1.5 minutes. The cause is thought to be neurobiologically and genetically determined. However, one should not exclude the possibility that in some instances it may have a pure psychological cause. Although specific research into its prevalence has not yet been performed, it is thought to be about 2% to 5%.³

Some men with lifelong PE experience an ejaculation during foreplay (ejaculatio ante portas); other men, as soon as their penis touches the vagina. Usually men with anteportal ejaculation are only able to penetrate for about 10 to 20 seconds. The majority of men with lifelong PE can stay in the vagina for a maximum of 30 to 60 seconds. Although some men and couples may cope well with the problem and experience sexual satisfaction, these men feel embarrassed, and depending on the consistency of the complaint, PE may lead to lower self-esteem, anticipatory anxiety, avoidance of sex, relationship problems, and female sexual complaints. Lifelong PE is not associated with thyroid dysfunction.⁷ Treatment consists of medication, usually an SSRI, with or without additional counseling.

The IELT in acquired PE is consistently short or very short (ie, less than 2 minutes) and results from either organic disorders, such as hyperthyroid dysfunction,⁸ prostatitis,⁹ or erectile dysfunction,¹⁰ or psychological problems, including relationship problems (eg, having sex while angry at the partner).¹¹ Its prevalence is unknown, but it is estimated to be in the lower range. Men with premature-like ejaculatory dysfunction complain of early ejaculations while their IELTs are actually in the normal range (ie, between 3 and 7 minutes) or even longer duration (ie, longer than 10 minutes). Its cause is most likely psychological, and its prevalence is estimated to be rather high, at about 15% to 20%. It is argued that treatment of this syndrome should consist of psychotherapy or counseling and not a priori of medication.⁶

Natural variable PE is actually not a real syndrome and is not pathological. Men may occasionally experience early ejaculations; the IELT is objectively short or may be perceived as short. Its prevalence is, as yet, unknown. Natural variable PE is most likely a normal variation of ejaculatory performance. Treatment should consist of patient reassurance and psychoeducation to explain that irregular early ejaculation is a normal variation.³

Diagnosis

Lifelong PE, acquired PE, natural variable PE, and premature-like ejaculatory dysfunction are diagnosed by taking a brief medical and sexual history with special attention to the duration of the ejaculation time. The men often complain of rapid ejaculations, ejaculating too soon, or experiencing a lack of control. In general, men with lifelong PE are mentally and physically healthy. Sometimes it becomes an obsession, and in rare instances it may even lead to suicidal thoughts.¹² The reaction of the female partners differs. Quite a number cope well with PE; on the other hand, there are women who are disappointed, irritated, and angry about their partner's ejaculatory problems.

Psychotherapy

Although PE was initially treated mainly by psychoanalysis or psychoanalytic psychotherapy,¹³ behavioral therapy, particularly the stop-start method,¹⁴ either on its own or combined with the squeeze technique,¹⁵ became the first-choice treatment in the 1970s and 1980s.

However, despite anecdotal reports of its success, given the lack of evidence-based studies conducted according to current standards of evidence-based research, there is no hard evidence for the efficacy of behavioral psychotherapy in delaying ejaculation in the long term. However, it should be noted that whether or not psychotherapy is able to delay ejaculation, it may be helpful in strengthening coping strategies.

Evidence-based research

In the past decade, an evidence-based drug treatment research strategy has been developed by independent researchers. Apart from randomized, double-blind controlled study designs, drug treatment studies of PE should include a baseline and a drug treatment period in which the IELT is measured prospectively at each coitus using a stopwatch handled by the female partner.^16,17 Because the IELT distribution is skewed toward the positive, the IELT values should be logarithmically transformed and results should be reported as geometric mean IELT or median IELT. In addition, ejaculation delay should be expressed as percentage or fold-increase from baseline with 95% confidence intervals (CIs). Adverse effects should be assessed with a validated questionnaire. Moreover, adverse effects of on-demand treatment should be assessed on the day of drug intake and on the next day.

Daily drug treatment

Daily treatment with either clomipramine or some SSRIs effectively delays ejaculation. For lifelong and acquired PE, daily treatment with SSRIs or combined daily treatment with on-demand use of some SSRIs has become the first choice of treatment.^18,19 However, these drugs have not been approved by the FDA for the treatment of PE.

A meta-analysis of 35 clomipramine and SSRI daily treatment studies that were conducted between 1973 and 2003 revealed that the use of placebo may delay ejaculation to some extent.¹⁷ It was also shown that of all SSRIs, daily treatment with 20 mg of paroxetine exerts the strongest ejaculation delay. Expressed in fold-increase compared with baseline values and using the geometric mean IELT, it was shown that placebo exerts a geometric mean 1.4-fold IELT increase (95% CI, 1.2-1.7) and that SSRIs differ in their ability to delay ejaculation. The rank order (geometric mean fold-increase of IELT) was paroxetine, clomipramine, sertraline, and fluoxetine (Table).

Recommended daily treatment is 20 to 40 mg of paroxetine, 10 to 50 mg of clomipramine, 50 to 100 mg of sertraline, 20 to 40 mg of fluoxetine, 20 to 40 mg of citalopram, or 10 to 20 mg of escitalopram. Ejaculation delay usually starts a few days after drug intake; however, a clinically relevant effect only gradually occurs after 1 to 2 weeks. Most often the delay continues to exist for years as long as treatment is continued, but in some cases it may diminish after 6 to 12 months. The cause of this tachyphylaxis of SSRIs has not yet been clarified.

Patients should be informed about the short-term and long-term adverse effects of SSRIs. The short-term effects include fatigue, yawning, mild nausea, loose stools, and perspiration. These adverse effects are usually mild, start within the first 1 to 2 weeks of treatment, and most often gradually disappear within 2 to 3 weeks.

Although a comparative study has not yet been performed, drug treatment studies seem to indicate that in contrast to the adverse effects in patients with depression, diminished libido and erectile dysfunction are reported less often by healthy men who have lifelong PE and are not depressed. A rather rare adverse effect of SSRIs is bleeding.²⁰ Clinicians should caution patients about combining SSRIs with aspirin or NSAIDs because this may increase the risk of bleeding. A very rare adverse effect is priapism,²¹ and all patients using SSRIs should be advised about the risk for priapism and the need for immediate medical treatment.

One should not prescribe these drugs for the treatment of PE in men who are younger than 18 years. These drugs should be used with caution in young men who have a depressive disorder and who are at risk for developing suicidal thoughts. Long-term adverse effects include weight gain with an associated risk for type 2 diabetes mellitus.²² To prevent the occurrence of SSRI discontinuation syndrome, patients should be advised not to stop taking the medication abruptly.²³

On-demand drug treatment

The aim of on-demand treatment strategies is to delay ejaculation, preferably within 1 to 2 hours after drug intake. A disadvantage of on-demand drug treatment is that it may negatively interfere with the spontaneity of having sex and that adverse effects may occur a few hours after drug intake, which is usually during the hours of intimacy and coitus. A recent study showed that the majority (81%) of a sample of men with lifelong PE actually favored daily SSRI treatment to on-demand treatment with clomipramine and the use of topical anesthetics.²⁴ In general, on-demand use of SSRIs exerts much less ejaculation delay than daily SSRI treatment. On- demand use of 20 to 40 mg of clomipramine may delay ejaculation after 4 to 6 hours²⁵; however, this may lead to nausea on the same day or the following day.

Another on-demand treatment option is the use of topical local anesthetics such as lidocaine and/or prilocaine in the form of a cream or spray that reduce the sensitivity of the glans penis.²⁶ Although topical anesthetics lack systemic adverse effects, their use may lead to erectile difficulties because of too strong anesthesia of the penis. It may also lead to vaginal numbness, but this may be prevented with the use of a condom.

Recently, it has been suggested that dapoxetine, an SSRI with a short half-life, would be a breakthrough drug for on-demand treatment of PE.²⁷ However, in 2005 the FDA did not approve dapoxetine for this indication. In recent years, a few studies suggested efficacy of on-demand use of phosphodiesterase type-5 (PDE-5) inhibitors to delay ejaculation. However, a recent review of 14 studies found that the majority did not fulfill the current criteria of evidence-based research.²⁸ It was concluded that there is no convincing evidence that PDE-5 inhibitors are effective in delaying ejaculation. Yet, they may be useful to treat PE in men with comorbid erectile dysfunction.

A definitive cure for lifelong PE does not exist. After cessation of drug treatment, PE returns within a few days.

Conclusion

DSM-IV-TR definition of PE has been based on authoritative opinions. Recently, a new classification of 4 PE syndromes that is based on evidence-based clinical and epidemiological data has been proposed for the pending DSM-V. For about a decade, SSRIs have been increasingly used to treat PE. However, to date, there is no information on the percentage of men that use SSRIs to delay ejaculation. For that purpose, pharmaco-epidemiological research is needed. The very high prevalence rates of PE of 20% to 30% probably do not reflect the real percentage of men who are in need of drug treatment for PE. Drug treatment should be confined only to men who have lifelong PE and acquired PE. Men with normal and even long durations of IELT should not be treated a priori with medication but with counseling and psychoeducation.

Apart from the topical use of anesthetics and on-demand use of clomipramine, daily treatment with some SSRIs has been shown to be an effective way to treat lifelong PE. Despite their adverse effects, daily treatment with SSRIs is currently one of the best options to treat PE.

References:

References

1.

Waldinger MD, Schweitzer DH. Changing paradigms from a historical

DSM-III

and

DSM-IV

view toward an evidence based definition of premature ejaculation. Part I: Validity of

DSM-IV-TR

.

J Sex Med.

2006;3:682-692.

2.

Waldinger MD, Hengeveld MW, Zwinderman AH. Paroxetine treatment of premature ejaculation: a double-blind, randomized, placebo-controlled study.

Am J Psychiatry.

1994;151:1377-1379.

3.

Waldinger MD, Schweitzer DH. Changing paradigms from a historical

DSM-III

and

DSM-IV

view toward an evidence-based definition of premature ejaculation. Part II: Proposals for

DSM-V

and

ICD-11

.

J Sex Med.

2006; 3:693-705.

4.

St. Lawrence JS, Madakasira S. Evaluation and treatment of premature ejaculation: a critical review.

Int J Psychiatr Med.

1992;22:77-97.

5.

Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology.

J Sex Marital Ther.

1989;15:130.

6.

Waldinger MD. The need for a revival of psychoanalytic investigations into premature ejaculation.

J Men's Health Gender.

2006;3:390-396.

7.

Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH. Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction.

J Sex Med.

2005;2: 865-870.

8.

Carani C, Isidori AM, Granata A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients.

J Clin Endocrinol Metabol.

2005; 90:6472-6479.

9.

Screponi E, Carosa E, Stasi SM, et al. Prevalence of chronic prostatitis in men with premature ejaculation.

Urology.

2001;58:198-202.

10.

Jannini EA, Lombardo F, Lenzi A. Correlation between ejaculatory and erectile dysfunction.

Int J Androl.

2005; 28:40-45.

11.

Althof SE. Psychological treatment strategies for rapid ejaculation: rationale, practical aspects, and outcome.

World J Urol.

2005;23:89-92.

12.

Assalian P. Guidelines for the pharmacotherapy of premature ejaculation.

World J Urol.

2005;23:127-129.

13.

Abraham K. Ueber Ejaculatio Praecox [in German].

Zeitschr Aerztl Psychoanal.

1917;4:171-186.

14.

Semans JH. Premature ejaculation: a new approach.

South Med J.

1956;49:353-358.

15.

Masters WH, Johnson VE. Premature ejaculation.

Human Sexual Inadequacy.

Boston: Little, Brown and Co; 1970:92-115.

16.

Waldinger MD. Towards evidence-based drug treatment research on premature ejaculation: a critical evaluation of methodology.

Int J Impot Res.

2003;15:309-313.

17.

Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis.

Int J Impot Res.

2004;16:369-381.

18.

Waldinger MD, Olivier B. Utility of selective serotonin reuptake inhibitors in premature ejaculation.

Curr Opin Investig Drugs.

2004;5:743-747.

19.

Moreland AJ, Makela EH. Selective serotonin-reuptake inhibitors in the treatment of premature ejaculation.

Ann Pharmacother.

2005;39:1296-1301.

20.

Weinrieb RM, Auriacombe M, Lynch KG, Lewis JD. Selective serotonin re-uptake inhibitors and the risk of bleeding.

Expert Opin Drug Saf.

2005;4:337-344.

21.

Ahmad S. Paroxetine-induced priapism.

Arch Intern Med.

1995;155:645.

22.

Fava M, Judge R, Hoog SL, et al. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment.

J Clin Psychiatry.

2000;61:863-867.

23.

Black K, Shea C, Dursun S, Kutcher S. Selective serotonin reuptake inhibitor discontinuation syndrome; proposed diagnostic criteria.

J Psychiatry Neurosci.

2000; 25:255-261.

24.

Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH. Majority of men with lifelong premature ejaculation prefer daily drug treatment: an observational study in a consecutive group of Dutch men.

J Sex Medicine.

In press.

25.

Segraves RT, Saran A, Segraves K, Maguire E. Clomipramine versus placebo in the treatment of premature ejaculation: a pilot study.

J Sex Marital Ther.

1993;19:198-200.

26.

Berkovitch M, Keresteci AG, Koren G. Efficacy of prilocaine-lidocaine cream in the treatment of premature ejaculation.

J Urol.

1995;154:1360-1361.

27.

Pryor JL, Althof SE, Steidle C, et al. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials.

Lancet.

2006;368:929-937.

28.

McMahon CG, McMahon CN, Leow LJ, Winestock CG. Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review.

BJU Int.

2006;98:259-272.