Managing Early Ejaculation: What Does the Future Hold?

Abstract

Recent attention in the field of male sexual dysfunction has focused on erectile dysfunction. However, premature ejaculation (PE) is an extremely common condition that warrants clinical study and exploration of pharmacologic treatments. Until recently, PE was thought to be a behavioral problem for which the best remedy was a learned control technique. However, some drugs currently on the market, including sildenafil and the selective serotonin reuptake inhibitors, appear to have efficacy in the treatment of PE. More research is needed before FDA approval of such agents for this indication, but more and better options for men with PE are anticipated as attention to ejaculatory disorders grows and, hopefully, the associated stigma decreases.

The field of sexual dysfunction continues to grow and, what began several decades ago with a focus on male erection, now encompasses female disorders as well. A recent literature search of the National Library of Medicine database yielded 15,506 entries for the term “male sexual dysfunction,” compared with 7939 for “female sexual dysfunction.” This increased awareness of and interest in the field is not surprising, as the introduction of oral pharmacologic therapy for erectile dysfunction (ED) has brought this term into the twenty-first century popular lexicon (with thanks to former Senator Bob Dole and others).

The prevalence of ED has been widely recognized since the landmark epidemiologic studies of McKinlay and colleagues in the early 1990s.¹ But what about other disorders of male sexual function? In particular, ejaculatory disorders and early or premature ejaculation (PE), although highly prevalent, have received little attention. The National Library of Medicine database contained only 290 entries for PE, yet community-based studies indicate that nearly one third of all men suffer with the condition.² How is this disorder defined, what causes it, and how can we treat it?

Definition and Prevalence

There is no clear consensus on the definition of PE, although the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria are generally accepted³:

1. Persistent or recurrent ejaculation with minimal stimulation before or shortly after penetration and before the person wishes it. (The clinician must take into account the factors that affect duration of the excitement phase, such as age, novelty of the sex partner or situation, and recent frequency of sexual activity.)

2. The disturbance causes marked distress or interpersonal difficulty.

3. The condition is not due exclusively to the direct effects of a substance (eg, withdrawal from opioids).

The DSM-IV definition is intentionally broad, but recent studies give some indication of what should be considered normal versus early ejaculation. Rowland and colleagues⁴ compared ejaculatory response during coitus and masturbation in 26 men with PE with that in 13 age-matched, sexually functional men. Mean ejaculatory latency during vaginal penetrative sex was 1.5 minutes in the PE group and 5.6 minutes in the control group. Ejaculation during masturbation yielded different results, with men with PE having latency times similar to those of controls (approximately 4.5 minutes). Furthermore, the frequency of reported sexual activity (intercourse or masturbation) was similar in both groups. Thus, the long-held theory regarding the cause of PE—that it results from long intervals between attempts to ejaculate or fewer opportunities to learn control—should be seriously questioned. PE has also been described as either “global” or “situational” in reference to either a lifelong or an acquired problem. At some time in their lives, all men have probably experienced an episode of ejaculation before they desired it; thus, situational PE is likely an extremely common problem.

The length of time from the beginning of stimulation (usually during vaginal penetration) until ejaculation is the measure most reported in PE studies.⁵ Other measures have also been reported, such as number of intravaginal thrusts.⁶ These measures are, at best, somewhat subjective and generally difficult to reproduce. A recently developed device attempts to solve this problem by applying continuous vibratory stimulation to the penis and measuring ejaculatory latency times.⁶

Epidemiology

Recent studies from primary care settings place the prevalence of PE from 31% in the United States⁷ to as high as 66% in Germany.⁸ Lower estimates, ranging from 10% to 25%, have been reported from sexual dysfunction clinics.⁹ Despite the prevalence of PE, there is an obvious stigma associated with the condition and it is likely underreported.

Physiology of Ejaculation

The process of ejaculation is under both central and peripheral control. Efferent sympathetic nerves from the spinal segments T12 to L2 form the lumbar sympathetic ganglia. These encircle the aorta and coalesce in the midline to form the hypogastric plexus just below the aortic bifurcation. They give rise to the hypogastric nerve, which terminates as postganglionic fibers at the bladder neck, seminal vesicles, vasa, and paraprostatic tissues.

Acetylcholine acts as a neurotransmitter while sympathetic activity stimulates contraction at the bladder neck, seminal vesicles, and vasa. The ejaculatory reflex results from somatic stimulation of the bulbocavernous and ischiocavernosus muscles and is controlled by the pudendal nerve. The central control of this process is not as well understood, but the locus ceruleus and the medial preoptic area have been identified as important cortical centers.

Ejaculation generally occurs because of a reflex mechanism initially triggered by stimulation of the penis via pudendal sensory nerves, with communication to the spinal cord and the sensory cortex. The secondary reflex is completed after activation of the efferent somatic fibers to the ischiocavernosus and other perineal muscles.

Why does this reflex occur in some men before they desire it? In the past, this was thought to be largely a behavioral problem. Recently, however, investigators have questioned whether the local penile response may be altered in men with PE. Xin and colleagues¹⁰ investigated penile sensory levels using biothesiometry in men with PE and compared them with normal levels. In men without PE, measurements of vibratory threshold increased with age, whereas, in men with PE, they were significantly decreased regardless of age (P < .001).

In follow-up studies, the investigators further examined penile hypersensitivity by evaluating somatosensory evoked potential in men with PE and in controls.¹¹ The mean latencies of dorsal nerve and glans penis somatosensory evoked potentials, respectively, were 1.51 and 6.80 milliseconds shorter in men with PE than in controls. The authors therefore concluded that men with PE have greater cortical representation of sensory stimuli from the penis, which facilitates PE. This idea has been challenged by other investigators who have not been able to document penile hypersensitivity in men with PE and suggest that other somatic or cognitive factors are responsible.¹²

Evaluation

Because PE and ED may coexist, it is important to clearly distinguish between these 2 common conditions in men presenting with sexual dysfunction. A detailed and complete sexual history should be obtained for all patients; the diagnosis of PE is largely made from self-report. Patients should be questioned about frequency and duration of activity required for ejaculation, as well as whether the problem exists with certain types of sexual stimulation versus others (eg, masturbation, oral sexual activity, vaginal intercourse).

Genital physical examination should also be performed, although few abnormalities associated with PE have been reported. Laboratory and physiologic testing using standard techniques, such as Doppler ultrasonography or biothesiometry, is generally unrevealing. New devices that can stimulate patients to ejaculation may be useful in certain circumstances.⁶

Treating PE

As early as 1956, Semans¹³ described the pause technique for the treatment of PE. Masters and Johnson¹⁴ modified this to the pause/squeeze technique in 1970. Patients were advised to cease thrusting or any other penile stimulation at the point at which ejaculation seemed inevitable, forcibly squeeze the glans penis, and then resume activity.¹⁵ The rationale behind this process was to train the man to recognize the typical premonitory sensation immediately preceding ejaculation and, thus, lead to better control. As late as the early 1990s, this technique was still believed to be the most appropriate treatment choice for PE.¹⁶ Nevertheless, pharmacologic therapy was beginning to gain proponents.

Pharmacologic Therapy

Selective serotonin reuptake inhibitors (SSRIs) were the first class of pharmacologic agents widely used to treat PE (Table 1). In 1980, Goodman¹⁷ evaluated clomipramine for the treatment of PE and found it to be superior to placebo. Cooper and Magnus¹⁸ experimented with the β-blocker propranolol in 1984, but results showed no improvement in men with PE. Beretta and colleagues¹⁹ evaluated phenoxybenzamine, a nonspecific α-adrenergic antagonist, in 15 men with PE, 8 of whom reported improvement in the condition. Some study patients reported a “dry ejaculation,” which most likely represented retrograde ejaculation. α-Blockers are known to cause bladder neck relaxation and also affect seminal emission and, potentially, vasal smooth muscle contraction. No other α-blockers, however, have been reported to be useful in treating ejaculatory disturbances.

Table 1.

Pharmacologic Therapy for Premature Ejaculation

Study	Agent	Reported Benefit
Goodman17	Clomipramine	Superior to placebo
Abdel-Hamid et al22
McMahon and Touma21	Paroxetine	Superior to placebo
Abdel-Hamid et al22
Kim and Paick20	Sertraline	Superior to placebo
Abdel-Hamid et al22
Beretta et al19	Phenoxybenzamine	Minor benefit
Cooper and Magnus18	Propranolol	No efficacy
Abdel-Hamid et al22	Sildenafil	Superior to placebo

Sertraline, another SSRI, has also been proposed as a treatment of PE. Kim and Paick²⁰ reported increased ejaculatory latency times, from 23 ± 19 seconds before treatment to 5.9 ± 4.2 minutes after use of sertraline, 50 mg daily. Similar results were achieved with sertraline, 50 mg or 100 mg, used on an as-needed basis. Peak plasma levels are achieved at 4 to 8 hours; thus, the authors recommend taking the drug in the early evening when intercourse or sexual activity is anticipated.²⁰

McMahon and Touma²¹ reported results of 2 single-blind, placebo-controlled, crossover studies of the SSRI paroxetine. Mean pretreatment ejaculatory latency time was less than 30 seconds in both studies. In the first study, patients received paroxetine, 20 mg, or placebo 3 to 4 hours before intercourse. Crossover occurred after 4 weeks of treatment and an additional 3-week drug-free washout period. At 4 weeks, mean ejaculatory latency was 3.2 minutes in the paroxetine group and 0.45 minutes in the placebo group (P < .001). No adverse events were reported.

In the second study, men received paroxetine, 10 mg, or placebo daily for 3 weeks, followed by paroxetine, 20 mg, or placebo as needed 3 to 4 hours before anticipated sexual activity. Mean ejaculatory latency time was 4.3 minutes in the daily-paroxetine phase and 5.8 minutes in the as-needed phase, compared with 0.9 minutes and 0.6 minutes in the daily and as-needed placebo phases, respectively (P < .001). Adverse events, including anejaculation, anorexia, decreased libido, and gastrointestinal upset, were reported in 17% of patients. This study seems to indicate that better ejaculatory control is achieved with initial daily treatment followed by as-needed treatment thereafter.

Recently, Abdel-Hamid and colleagues²² compared clomipramine, sertraline, paroxetine, sildenafil, and the pause/squeeze technique for the treatment of PE in a prospective, randomized, double-blind crossover study (not placebo-controlled). Thirty-one men with PE were randomized to receive 4 weeks of treatment with one of the 5 treatment modalities. At the end of the study, all subjects noted significant improvement from baseline. Sildenafil was superior to all other treatments in prolonging ejaculatory latency time; clomipramine, sertraline, and paroxetine were all superior to the pause/squeeze technique. The reason for sildenafil’s superiority is unclear but may be explained by central effects involving increased cyclic guanosine monophosphate activity. Many clinicians currently recommend a combination of sildenafil and an SSRI, particularly for patients who complain of both PE and ED.

Topical Agents

Choi and colleagues²³ recently reported on an agent that is applied to the ventral penile area and has previously been shown to increase penile vibratory threshold and prolong ejaculatory latency, as well as reduce the amplitude of penile somatosensory evoked potentials.²⁴ This topical agent, called SS cream, is a mixture of Ginseng Redix Alba, Angelicae Gigantic Radix, Cistanchis Herba, Zanthoxylli Fructs, Torlidis Semen, Asiasari Radix, Caryophylli Flos, Cinnamoni Cortex, and Bufonis Veneum.

A randomized, double-blind, placebo-controlled trial was conducted in 106 men with lifelong PE. Subjects were instructed to apply the cream to the glans and frenular area of the penis 1 hour before intercourse. Mean ejaculatory latency time was prolonged from 1.37 ± 0.12 minutes to 10.92 ± 0.95 minutes in the treatment group versus 2.45 ± 0.29 minutes in the placebo group. Mild local burning was reported in 18% of treatment subjects; no adverse partner effects were observed. SS cream, which was developed in Korea, is not commercially available in the United States.

Topical lidocaine and prilocaine cream (EMLA cream, lidocaine 2.5% and prilocaine 2.5%, AstraZeneca Pharmaceuticals) has been anecdotally reported to have some efficacy in the treatment of PE. This agent should probably be used in conjunction with a condom.

Herbal Agents

Numerous over-the-counter agents are advertised for the treatment of PE. These range from oral remedies to creams and other topical products. A recent Internet search revealed products such as “Indian God Lotion,” “Quang’s Solution,” “Stud 100,” and “Iron Wood.” Because none of these agents is regulated by the FDA, their contents, as well as their efficacy, are unknown.

Conclusion

Of the 3 major forms of male sexual dysfunction—ED, PE, and decreased libido—PE is probably the most common. All men are likely to experience PE at some point in their lives. Although the precise definition of the disorder is unclear, with most studies pointing to an ejaculatory latency time of less than 1 to 2 minutes, the condition is bothersome enough to most men and/or their partners to consider treatment. The phosphodiesterase-5 inhibitor sildenafil and the SSRIs sertraline, clomipramine, and paroxetine appear to have potentially promising therapeutic roles. It should be emphasized that none of these drugs has been approved by the FDA for the treatment of PE. However, given the prevalence of this condition and the potentially large market for agents to treat it, these and other similar products are likely to be approved for this indication at some time in the future.

Main Points.

• Although there is no clear consensus on the definition of premature ejaculation (PE), it is generally accepted that PE consists of persistent or recurrent ejaculation with minimal stimulation before or shortly after penetration and before the person wishes it, which causes marked distress or interpersonal difficulty and is not due exclusively to the direct effects of a substance.

• A biothesiometry study by Xin and colleagues concluded that men with PE have greater cortical representation of sensory stimuli from the penis; however, other studies have failed to document penile hypersensitivity and, therefore, other somatic or cognitive factors may be responsible.

• Because self-report is often more revealing than physical findings or standard laboratory and physiologic testing, a thorough sexual history is the most important tool in establishing the diagnosis of PE.

• Although not yet FDA-approved for this indication, sildenafil, a topical treatment called SS cream, and some of the selective serotonin reuptake inhibitors (sertraline, clomipramine, and paroxetine) have been shown to be promising potential therapies for PE (and perhaps more effective than previous remedies, such as the “pause/squeeze” technique).