Premature ejaculation: Management in primary care

The most common dysfunctions of the ejaculatory process seen in primary care are ejaculation prior to the time desired by the patient and/or his partner (premature or rapid ejaculation), painful ejaculation (dysorgasmia), absence of ejaculation (anejaculation), blood with ejaculation (hematospermia), and retrograde ejaculation (usually postsurgical or associated with alpha-blocker treatment for benign prostatic hypertrophy). Of these, premature ejaculation (pEJ) is by far the most prevalent, affecting as many as 39% of men in the general community.1

Nonetheless, men are often reluctant to acknowledge the presence of pEJ, no pharmacotherapeutic agent has yet been FDA-approved for its treatment, and the education of primary care clinicians about ejaculatory dysfunctions has often been scanty. Because pEJ may cause distress for the patient and/or his partner, and clinical trials have demonstrated the efficacy of a variety of remedies, clinicians may wish to familiarize themselves with the appropriate diagnosis and management skills necessary for successfully addressing this problem.

DEFINITION Defining pEJ has been difficult for investigators because of a lack of adequate population-based data to establish normative boundaries for either the duration of intravaginal intercourse or number of thrusts until ejaculation. Similarly, quantifying what constitutes appropriate maintenance of erection prior to ejaculation from the vantage point of partner satisfaction has been elusive.

The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) has defined pEJ as "persistent or recurrent ejaculation with minimal sexual stimulation before, upon, or shortly after penetration and before the person wishes it."2 While this definition probably accurately describes most men who suffer from pEJ, it lacks finite boundaries that might make case definition simpler for clinicians.

Furthermore, all definitions of pEJ should contain some notion of "bother," since if the patient or his partner is not bothered by the duration of intercourse, no treatment is required regardless of the brevity of the experience. For the discussion that follows, we consider any of the 3 following operational descriptors, as a complement to the DSM-IV definition, adequate for the functional delineation of pEJ:
A consistent experience of unwanted inability to delay ejaculation beyond 2 to 3 minutes of intromission
A consistent experience of ejaculation prior to 7 minutes of intromission that is problematic for the patient or partner satisfaction
A 50% or greater decrease in the amount of time to ejaculation compared with a previously established long-term pattern of sexual experience, which might also be labeled secondary pEJ.

The vast majority of patients with pEJ will be described by one or more of these criteria. Because pEJ may affect heterosexual or same-sex encounters, no terminology involving vaginal intromission is used, although readers should be aware that a good deal of the literature about pEJ uses intravaginal latency as a metric.

The rationale behind the first descriptor is the fact that, despite the lack of adequate normative population data, an average duration of intercourse of 4 to 7 minutes has been reported, leading to the consideration that duration substantially less than this, if unwanted, should clearly qualify as pEJ. Similar issues confirm the utility of the second descriptor, so that when intercourse lasts less than 7 minutes, if the patient finds this duration insufficient, consideration may be given to offering treatment. Lastly, pEJ may become problematic when a patient reports a departure from his usual experience of ejaculatory timing. For instance, patients with prostatitis may report changes in ejaculatory latency, with a trend toward earlier ejaculation, difficulty maintaining an erection, or both. Although typically a transient phenomenon, opioid withdrawal has also been associated with pEJ.3

YES, BUT WHY BOTHER? According the one survey, pEJ is epidemiologically the most common sexual dysfunction reported by American men, with an overall prevalence of 29%.4 Yet, although pEJ has not been a common presenting complaint in primary care, men and/or their partners may be quite distressed by it. Perceptions of the problem on the part of both patients and clinicians tend to preclude disease identification and treatment. Patients often do not complain about pEJ because they are embarrassed by the condition, there is minimal public awareness that pEJ is a legitimate health issue, and there is also a lack of insight that safe, effective treatments are available. Clinicians may not be familiar with an appropriate mode of inquiry, may have had scant guidance on pharmacotherapeutic management, and, despite the burden of distress that the disorder may cause to patients, may perceive pEJ as a low-priority disorder.

There is reason to be optimistic about pEJ management. Men who were dissatisfied with prior treatments may find newly discovered interventions more attractive. The widespread public awareness of the role of phosphodiesterase-5 (PDE-5) inhibitors in erectile dysfunction (ED) may facilitate disclosure of other sexual dysfunctions to the clinician. ED has increasingly moved into the bailiwick of primary care clinicians, so the opportunity for discussion of various sexual dysfunctions has also increased. Finally, with pharmacotherapy and/or counseling, most patients will find a satisfactory degree of pEJ improvement or resolution.

The epidemiologic patterns of pEJ are surprising to some clinicians. The disorder is most common between ages 20 to 40 years (average age, 33.1), and cases are fairly evenly distributed between primary (lifelong) and secondary disease (occurring after an established period of normal ejaculatory function). In men older than age 40 years, primary pEJ becomes the dominant category.5

DIAGNOSIS Primary care clinicians tend to prioritize the line of inquiry during a patient visit by disease-state hierarchy, so that cardiovascular disease, hypertension, and diabetes often obtain first notice and follow-up. Quality of life issues such as pEJ may be significantly problematic for patients or their partners and deserve our attention if they are a priority for the patient. Because clinical inquiry into sexual function has been relatively uncommon in the recent past, it is usually incumbent on the clinician to initiate the dialogue.

The diagnosis of pEJ occurs via the history; appropriate laboratory tests and physical examination rule out secondary causes. Clinicians need to be explicit in their inquiry if meaningful information is to be obtained. A variety of appropriate questions may help initiate discussion of sexual matters. Here is an example of the universal-to-specific shepherding technique: "Mr Anderson, many men who take SSRIs notice changes in their ejaculation. Has this been a problem for you?"

Some clinicians, however, consider inquiry about sexual function to be one of the vital signs of lifestyle, hence this approach: "Mr Anderson, I would like to ask you some personal questions at this point, and of course we can leave out any questions that make you uncomfortable or that you do not wish to answer. Are you having any difficulties with sexual function? Specifically, do you experience any problems with the duration of intercourse or orgasm?"

The key issues that need to be elucidated regarding ejaculatory function include time to ejaculation, whether time to ejaculation is within the patient's control, and whether the ejaculatory experience causes the patient (or his partner) distress.5 The following questions are appropriate, revolve around these issues, and also target possible causes:
Typically, how long does sexual activity last before orgasm?
Is this a change from your prior experience?
Is the duration of intercourse you are experiencing a problem for you or your partner(s)?
If duration of intercourse is problematic, what strategies have you tried to remedy the situation?
Have there been any emotional or psychological stressors that occurred around the time you first noticed the changes in your sexual function?
Are there any medications, herbs, vitamins, or other substances that you started taking around the time you noticed changes in your ejaculatory function?

ETIOLOGY When pEJ is associated with a medication, a noteworthy psychological stress, or physical trauma, little further investigation for culpable sources is necessary. Unfortunately, the cause is commonly unknown and, in many cases, may be a combination of biologic and psychological factors.

Supporting the role of serotonin in ejaculatory function is the consistent impact of delayed ejaculation in men who receive selective serotonin reuptake inhibitors (SSRIs) for depression. Much of the other data ascribing pEJ to various neurologic or hormonal factors is based on rat studies, without convincing confirmation in humans. Data from the 1970s by Masters and Johnson reported simple counseling techniques for pEJ had success rates as high as 97%, a statistic which would lend credence to the dominantly psychogenic components of the etiology. Recently, these early data have been criticized because of lack of placebo controls, small data sets, and insufficient replication. Hypogonadism has rarely been associated with pEJ, but correction of hypogonadism with anastrozole did not improve pEJ.6

TREATMENT The goal of treatment for pEJ is to delay ejaculation sufficiently to relieve the distress experienced by the patient or his partner. Available methods include behavioral therapy, counseling, sexual stimulation techniques, pharmacotherapy (topical and systemic), and mechanical therapies such as vacuum pumps and penile constriction rings.

Counseling Since pEJ is very often solely psychogenic, counseling is an appropriate tool that is usually provided by sex therapists. Clinicians may also be able to provide simple instructions about distraction techniques, Kegel exercises, and stop-start vaginal intromission methods that will allow the patient to develop a sense of ejaculatory control. The usefulness of such interventions is largely unknown, but anecdotal reports suggest some efficacy.

Physical maneuvers include the squeeze technique and penile constriction devices. For the squeeze technique, the patient and his partner are instructed that when the patient feels a sensation of ejaculatory imminence, he should withdraw his penis and his partner should provide a firm squeeze (2-3 seconds) at the base of the glans penis. Often, this withdrawal from vaginal stimulation, cessation of thrusting, and contrasexual stimulus will produce a sufficient deescalation of ejaculatory imminence to allow the couple to resume intercourse a few seconds later.

Men who use a vacuum constriction device will be familiar with the incorporation of a constricting band (constriction ring) to maintain penile turgidity during intercourse. Even after ejaculation, the presence of a constriction band at the base of the penis will maintain turgidity sufficient for vaginal penetration and continued vaginal thrusting in most patients. Once the patient has a constriction device on the base of his penis and knows that the erection will be maintained even after ejaculation, ejaculatory anxiety is reduced, and the subsequent reduction in sympathetic tone may be useful in extending vaginal latency. A popular adjustable constriction ring has the brand name Actis. Penile constriction rings are very inexpensive and may be used many times before they need to be replaced.

Patients may consider wearing one or more condoms to reduce penile glans sensitivity. Topical agents that reduce glans sensitivity are also effective, but the practicality of these agents is limited by the need to wash them off after intercourse and to use barrier methods to prevent topical application on the partner.

Pharmacotherapy In the authors' experience, most patients who present with pEJ want pharmacotherapy. Most of the experience with neurohumoral modulation has been obtained with various SSRIs or with tricyclic antidepressants (TCAs), particularly clomipramine. Consonant with the literature that pEJ may be accompanied by a reduction in serotoninergic neurotransmission,7 the most common medications used for pEJ are SSRIs.

Widespread use of SSRIs for depression soon led to the observation that SSRIs could cause ejaculatory delay, or even anejaculation, in men without prior ejaculatory dysfunction. It was a logical next step to study these agents in men with pEJ.8 Adding credence to the serotonin-modulation theory of ejaculatory dysfunction, withdrawal of citalopram has been associated with pEJ.9 A variety of SSRIs have been studied for pEJ, most of them producing favorable effects for prolonging ejaculatory latency. Even though the data on clomipramine, a TCA indicated for obsessive-compulsive disorder, appear to be equally favorable, the adverse-effect profile of TCAs may limit their use.

Three primary methods of drug administration have proved to be efficacious: medication on demand (within hours of anticipated intercourse), maintenance medication (such as a daily regimen), or sequential medication (a course of daily medication for 4-6 weeks, followed by medication on demand). All the SSRIs studied so far have had some favorable effects, but comparison studies indicate that paroxetine may be the most effective.10 With maintenance therapy, patients can generally anticipate a 3- to 10-fold increase in ejaculatory latency time. Consequently, men who have not been able to delay ejaculation beyond 30 seconds to 1 minute might be able to enjoy prolongation of intercourse for 1.5 to 7 minutes. Note that, for all the agents studied to date, pEJ is an off-label indication.

Because paroxetine has been demonstrated to have the most pronounced effect on ejaculatory latency, it may be considered as a drug of choice, with therapy initiated at 20 mg/d. Failure to respond within 4 weeks of daily medication (titrated to 40 mg/d of paroxetine—or 100 mg/d of sertraline, 40 mg/d of fluoxetine, or 50 mg/d of clomipramine) should prompt consideration of another method of treatment.11 Although higher dosages of SSRIs and TCAs may produce greater prolongation of ejaculatory latency, side effects may also increase incrementally. Since some patients will prefer one SSRI over another, or the metabolic effects of some SSRIs may be problematic (for example, paroxetine and fluoxetine are very potent cytochrome P-450IID6 inhibitors), clinicians may consider sertraline, which lacks significant cytochrome P-450 interactions and is associated with less sedation than paroxetine.

Rather than adhering to a daily regimen, patients may wish to try on-demand medication. Although scant data support this use, clomipramine, 25 to 50 mg administered within 4 to 6 hours of intercourse, has shown some efficacy for pEJ, with a duration of up to 15 hours.11 Initial data suggest that sildenafil may be an effective treatment for pEJ in some men. One comparison trial of patients with lifelong pEJ that evaluated SSRIs, clomipramine, sildenafil, and the squeeze technique found sildenafil to be the most efficacious, but because this study had no placebo control and showed other methodologic limitations, the results must be considered preliminary.1,12

The effectiveness of combination pharmacotherapy is supported by limited, but promising, data. A prospective study of 80 patients compared combination therapy with a regimen of paroxetine (10 mg/d for 21 d, followed by 20 mg/d on demand) with or without sildenafil. Combination therapy was more effective: Monotherapy increased mean ejaculatory latency time from 0.33 minutes (baseline) to 4.2 minutes at 6 months, whereas combination therapy improved ejaculatory latency from 0.35 minutes (baseline) to 5.3 minutes at 6 months and was associated with greater intercourse satisfaction.13

Because some men will continue to use SSRIs for pEJ treatment on a long-term basis, it is appropriate to address medication safety with them. Like all pharmacotherapeutic agents, SSRIs may have problematic adverse effects. There is now also clearer recognition that there may be a population of individuals for whom SSRIs may transiently accentuate the risk of suicide or suicidal ideation. Hence, prior to initiating a program of sustained SSRI treatment, the clinician should be aware of the patient's status for depression and suicidal ideation, and inform him of this risk.

Topical treatment Topical anesthetics can improve ejaculatory latency time by reducing penile sensitivity, but excessive topical anesthesia can prevent erection due to lack of sensory input. In addition, unless a barrier method is used in conjunction with topical agents, application to the sexual partner may concomitantly reduce the partner's cutaneous sensitivity.

Examples of topical agents found to improve intravaginal ejaculatory latency time in randomized placebo-controlled trials include lidocaine 2%, and lidocaine 2.5%/prilocaine cream 2.5%.Data suggest that such agents may be applied 10 to 30 minutes before intercourse.