American Urological Association - Pharmacologic Management of Premature Ejaculation

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Home Guidelines Clinical Guidelines Premature Ejaculation (2004; Reviewed and Validity Confirmed 2010)

Pharmacologic Management of Premature Ejaculation

Published 2004; Reviewed and Validity Confirmed 2010

Epidemiological studies suggest that premature ejaculation (PE) may be the most common male sexual disorder. This clinical guideline discusses the evaluation and treatment of this condition.

Unabridged version of this Guideline [pdf]

Panel Members

Drogo K. Montague, MD, Co-Chairman; Jonathan Jarow, MD, Co-Chairman; Gregory A. Broderick, MD; Roger R. Dmochowski, MD; Jeremy PW Heaton, MD; Tom F. Lue, MD; Ajay Nehra, MD; Ira D. Sharlip, MD

Introduction

The three major forms of male sexual dysfunction are ejaculatory dysfunction, erectile dysfunction (ED), and decreased libido (hypoactive sexual desire disorder). While survey findings vary considerably, most epidemiological studies suggest that premature ejaculation (PE) (Although the terms early ejaculation and rapid ejaculation recently have been suggested as more accurate descriptions of this disorder, to prevent confusion, the common name premature ejaculation will be used throughout this document.) may be the most common male sexual disorder. Data from the National Health and Social Life Survey have revealed a prevalence of 21% in men ages 18 to 59 in the United States1. Using various definitions, other studies report prevalences ranging from less than 5% 2 to greater than 30% 3, 4, 5.

A universally accepted definition of PE has yet to be established. Masters and Johnson (1970) 6 proposed one of the earliest definitions that focused on the inability to delay ejaculation long enough for the woman to achieve orgasm fifty percent of the time, assuming that PE is the sole cause of the female anorgasmia. Kaplan (1974) 7 first suggested that PE is primarily a problem of voluntary control over timing of ejaculation, a concept on which the current definition is based. The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (4th ed., Text Revision) (DSM-IV TR) (2000) 8 defines PE with an added emphasis on the emotional and interpersonal impact of ejaculation that occurs earlier than the male desires. Premature ejaculation has been subclassified into two forms: a primary (lifelong) form that begins when a male first becomes sexually active and a secondary (acquired) form 9, 10. The present guidelines and recommendations are based on the following definition, which assumes the absence of partner sexual dysfunction:

Premature ejaculation is ejaculation that occurs sooner than desired, either before or shortly after penetration, causing distress to either one or both partners.

The exact etiology of PE is unknown. Psychological/behavioristic and biogenic etiologies have been proposed. Consequently, the treatment of PE has encompassed psychological, behavioral, and pharmacologic interventions. Current treatments are largely based upon logical solutions (decreasing sensory input), behavior modification therapies, and observations of drug side effects (those with serotonin reuptake inhibiting activity). This guideline will address only pharmacologic therapies, as other therapies are not routinely prescribed by our target audience.

To facilitate informed treatment decisions by physicians and their patients, recommendations on the use of medications currently available in the United States are provided. The majority of the recommendations contained herein are based on a consensus of expert opinion following review of the literature. In some cases, expert consensus is supplemented with a focused review of the limited data. This guideline does not preempt physician judgment in individual cases. Variations in patient subpopulations, physician experience, and available resources necessarily will influence choice of clinical strategy. Adherence to the recommendations presented in this document cannot assure a successful treatment outcome.

For ease of review, the recommendations are bolded and followed by supporting text. The evidence supporting the recommendations is summarized in Appendices 1 to 3.

Methodology

The Erectile Dysfunction Guideline Update Panel (hereafter the Panel) of the American Urological Association (AUA) was convened in April 2000 at the request of the AUA Board of Directors. The Practice Guidelines Committee of the AUA selected the Panel Co-chairmen, and the full Panel roster was assembled by invitation to experts in the field. The Panel evaluated several topics for possible guideline development. Premature ejaculation was selected because of its high prevalence and the availability of a defining body of literature.

Using the MEDLINE® database with MeSH headings related to ejaculatory dysfunction, initial literature searches were performed limiting papers to reports of human studies published in English-language journals between 1966 and January 2001. Only a small number of articles provided outcomes data on PE. Additional studies were identified from references cited in these articles and from recommendations of individual Panel members. The MEDLINE search was last updated in October 2002. Even after the final literature search was completed, however, the Panel continued to scrutinize key references that were identified up until the peer review process.

From a review of abstracts, the Panel chairs selected articles with potentially usable information. Selected papers were reviewed in detail, and relevant data on efficacy and adverse events were extracted and listed in evidence tables (see Appendix 1). Only papers with outcomes data that were relevant to PE, involving pharmacologic treatments generally available in the United States, were included in the evidence tables. If the study was seriously flawed, the article was not considered. Summary tables of adverse event rates and effects of various treatments on latency were created to supplement the data captured in the evidence tables (see Appendices 2 and 3). A complete list of the 51 references that met all inclusion criteria is available in Appendices 4 and 5. The full Panel reviewed the evidence and summary tables at successive meetings.

Three major limitations were encountered in the evaluation of the evidence that precluded the ability to combine outcomes data and to perform study outcomes comparisons:

  • The lack of standardization in studying PE. Clinical trials employ a variety of definitions, entry criteria, physiological measurements and psychometric instruments for evaluation.
  • The lack of agreement in quantifying the amount of stimulation that patients experienced. Time to ejaculation is a function of many factors, not the least of which is the nature of the stimulation. The same stimulus may be excessive for one man but elicit little excitement in another. Furthermore, the lack of a consistent stimulus (partner variables, nature of sexual activity, presence or absence of foreplay, preference for single or multiple stimuli) precludes a rigorous experimental design.
  • The lack of consistency and accuracy in measurements of time to ejaculation and other outcomes. The most common outcome parameter, time to ejaculation, is either recorded at the time or documented later by recall. These measurements lack accuracy but generally are useful when applied consistently within a single study. Application across multiple studies in a meta-analysis is problematic because any methodological differences will compromise the ability to make a valid comparison. Other common outcome measures concern patient and partner satisfaction. A variety of assessment tools are used, and there is no assurance of comparability between studies.

The Panel determined that a meta-analysis was inappropriate due to the disparate outcome measures and populations in the existing studies. The amount of variation between studies also made other less rigorous forms of outcome estimation inaccurate. The Panel's recommendations were developed either solely by consensus or by consensus combined with a review of the available, though limited, evidence. Unless otherwise noted, the statistics cited in this document are derived from the evidence tables.

After this guideline was written, it was reviewed and approved by each member of the Panel and submitted for peer review by 57 physicians. Based on the results of peer assessment, revisions were made and the guideline was forwarded to the Panel again, to the Practice Guidelines Committee, and the Board of Directors of the AUA, all of which rendered approval.

Evaluation

Premature ejaculation is a self-reported diagnosis. A sexual history in which the patient uses language that explicitly communicates the circumstances of the condition is the fundamental basis of assessment with time to ejaculation as the most important feature. The opinion of a partner can provide a significant contribution to clinician understanding. A complete description is essential in distinguishing PE from ED, i.e., the inability to attain or maintain an erection, because these conditions frequently coexist. Moreover, some men are unaware that loss of erection after ejaculation is normal; thus, they may erroneously complain of ED when the actual problem is PE.

Guideline Statement 1

The diagnosis of PE is based on sexual history alone. A detailed sexual history should be obtained from all patients with ejaculatory complaints.

Discussion


Guideline Statement 2

In patients with concomitant PE and ED, the ED should be treated first.

Discussion


Treatment

Guideline Statement 3

The risks and benefits of all treatment options should be discussed with the patient prior to any intervention. Patient and partner satisfaction is the primary target outcome for the treatment of PE.

Discussion


Guideline Statement 4

Premature ejaculation can be treated effectively with several serotonin reuptake inhibitors (SRIs) or with topical anesthetics. The optimal treatment choice should be based on both physician judgment and patient preference.

Discussion


Future Research and Conclusions

Future Research

Deficiencies and inconsistencies in the design of and lack of reporting standards for clinical studies on PE have hindered attempts to identify best practices. Future research efforts using well-planned and well-executed randomized, controlled trials are needed to:

  • Determine ejaculation latency time in the general population;
  • Develop a consensus on the definition of PE;
  • Develop standardized, validated instruments to measure outcomes (i.e., patient/partner satisfaction and bother, ejaculatory latency);
  • Determine more precisely the efficacy and risks of drug therapies;
  • Determine ideal dosing regimens for SRIs (i.e., daily versus situational dosing regimens and whether loading is necessary prior to situational dosing);
  • Determine the optimal treatment duration and how or whether to discontinue therapy;
  • Determine the long-term acceptability of therapeutic agents to patients;
  • Determine the efficacy of combining pharmacologic and behavioral approaches to therapy; and
  • Identify the age-specific prevalence of PE.

Other authors29, 30 have made recommendations for reporting results in this field that should be considered by investigators studying PE.

Conclusions

A common male sexual disorder, PE traditionally has been treated with psychotherapy or behavioral therapy. This guideline is the first to address the pharmacologic treatment of PE. Although not approved by the FDA for this indication, oral antidepressants and topical anesthetic agents have been shown to delay ejaculation in men with PE and have minimal side effects when used for the treatment of PE. Treatment with oral antidepressants should be started at the lowest possible dose that is compatible with a reasonable chance of success. The choice of additional therapy is based on the patient and partner reports of efficacy, side effects, and acceptance of the therapy as well as on a regular review of alternative approaches. Support and education of the patient and, when possible, the partner are an integral part of PE therapy.

References

1. Laumann E.O., Paik A., and Rosen R.C. Sexual dysfunction in the United States: prevalence and predictors. JAMA, 281: 537, 1999.

2. Simons J.S. and Carey M.P. Prevalence of sexual dysfunctions: results from a decade of research. Arch Sex Behav, 30: 177, 2001.

3. Aschka C., Himmel W., Ittner E., and Kochen M.M. Sexual problems of male patients in family practice. J Fam Pract, 50: 773, 2001.

4. Frank E., Anderson C., and Rubinstein D. Frequency of sexual dysfunction in "normal" couples. N Engl J Med, 299: 111, 1978.

5. Metz M.E., Pryor J.L., Nesvacil L.J., Abuzzahab F. Sr, and Koznar J. Premature ejaculation: a psychophysiological review. J Sex Marital Ther, 23: 3, 1997.

6. Masters, W. H., & Johnson, V. E. Human Sexual Inadequacy. Boston : Little, Brown, 1970.

7. Kaplan, H. S. The New Sex Therapy: Active Treatment of Sexual Dysfunctions. New York: Brunner/Maazel, 1974.

8. Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision). Washington D.C.: American Psychiatric Association, 2000.

9. Godpodinoff M.L. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther, 15:130, 1989.

10. Williams W. Secondary premature ejaculation. Aust N Z J Psychiatry., 18:333, 1984.

11. Kara H., Aydin S., Yucel M., Agargun M.Y., Ocabas O., and Yilmaz Y. The efficacy of fluoxetine in the treatment of premature ejaculation: a double-blind placebo controlled study. J Urol, 156:1631, 1996.

12. Murat Basar M., Atan A., Yildiz M., Baykam M., and Aydoganli L.. Comparison of sertraline to fluoxetine with regard to their efficacy and side effects in the treatment of premature ejaculation. Arch Esp Urol,52: 1008, 1999.

13. Haensel S.M., Klem T.M., Hop W.C., and Slob A.K. Fluoxetine and premature ejaculation: a double-blind, crossover, placebo-controlled study. J Clin Psychopharmacol, 18: 72, 1998.

14. Waldinger M.D., Hengeveld M.W., and Zwinderman A.H. Paroxetine treatment of premature ejaculation: a double-blind, randomized, placebo-controlled study. Am J Psychiatry, 151: 1377, 1994.

15. Waldinger M.D., Hengeveld M.W., and Zwinderman A.H. Ejaculation retarding properties of paroxetine in patients with primary premature ejaculation: a double-blind, randomized, dose-response study. Br J Urol, 79: 592, 1997.

16. Waldinger M.D., Berendsen H.H., Blok B.F., Olivier B., and Holstege G. Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res, 92: 111, 1998.

17. Mendels J., Camera A., and Sikes C. Sertraline treatment for premature ejaculation. J Clin Psychopharmacol, 15: 341, 1995.

18. Althof S.E., Levine S.B., Corty E.W., Risen C.B., Stern E.B., and Kurit D.M. A double- blind crossover trial of clomipramine for rapid ejaculation in 15 couples. J Clin Psychiatry, 56: 402, 1995.

19. Balachandra K. Re: treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 single-blind placebo controlled crossover studies. J Urol, 166: 2325, 2001.

20. Atikeler M.K., Gecit I., and Senol F.A. Optimum usage of prilocaine-lidocaine cream in premature ejaculation. Andrologia, 34: 356, 2002.

21. Sahin H. and Birkan, M.K.. Re: efficacy of prilocaine-lidocaine cream in the treatment of premature ejaculation. J Urol, 156: 1783, 1996.

22. Abdel-Hamid I.A., El Naggar E.A., and El Gilany A.H. Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation. Int J Impot Res, 13: 41, 2001.

23. Fein RL. Intracavernous medication for treatment of premature ejaculation. Urology, 35: 301, 1990.

24. Salonia A., Maga T., Colombo R., Scattoni V., Briganti A., and Cestari A. A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol, 168: 2486, 2002.

25. Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy. Eur Urol, 28: 126, 1995.

26. Beretta G., Chelo E., Fanciullacci F., and Zanollo A. Effect of an alpha-blocking agent (phenoxybenzamine. in the management of premature ejaculation. Acta Eur Fertil, 17: 43, 1986.

27. Cooper A.J. and Magnus R.V. A clinical trial of the beta blocker propranolol in premature ejaculation. J Psychosom Res, 28: 331, 1984.

28. Shilon M., Paz G.F., and Homonnai Z.T. The use of phenoxybenzamine treatment in premature ejaculation. Fertil Steril, 42: 659, 1994.

29. Althof S.E. Evidence based assessment of rapid ejaculation. Int J Impot Res, 10: S74, 1998.

30. Rowland D.L., Cooper S.E., and Schneider M. Defining premature ejaculation for experimental and clinical investigations. Arch Sex Behav, 30: 235, 2001.

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