Premature Ejaculation

Premature (early) ejaculation—also referred to as rapid ejaculation—is the most common type of sexual dysfunction in men younger than 40 years. An occasional instance of premature ejaculation might not be cause for concern, but, if the problem occurs with more than 50% of attempted sexual relations, a dysfunctional pattern usually exists for which treatment may be appropriate.

Most professionals who treat premature ejaculation define this condition as the occurrence of ejaculation earlier than both sexual partners wish. This broad definition thus avoids specifying a precise “normal” duration for sexual relations and reaching a climax. The duration of intimate relations is highly variable and depends on many factors specific to the individuals involved.

For example, a male may reach climax after 8 minutes of sexual intercourse, but if his partner regularly climaxes in 5 minutes and both are satisfied with the timing, this is not premature ejaculation. Alternatively, a male might delay his ejaculation for up to 20 minutes of sexual intercourse, but if his partner, even with foreplay, requires 35 minutes of stimulation before reaching climax, he may still consider his ejaculation and subsequent loss of erection premature because his partner will not have been satisfied (at least, not through intercourse).

Because many females are unable to reach climax at all with vaginal intercourse, no matter how prolonged, the second situation described may actually represent delayed orgasm in the female partner rather than premature ejaculation in the male; the problem can be either or both, depending on the point of view. Such differences in perspective highlight the importance of obtaining a thorough sexual history from the patient (and preferably from the couple).

Premature ejaculation may be lifelong or acquired. Lifelong premature ejaculation applies to individuals who have had the condition since they became capable of functioning sexually (ie, post puberty).

Acquired premature ejaculation means that the condition began in an individual who previously experienced an acceptable level of ejaculatory control and, for unknown reasons, began experiencing premature ejaculation later in life. Acquired premature ejaculation is not related to a general medical disorder and usually is not related to substance inducement, though in rare cases, hyperexcitability might be associated with a psychotropic drug and resolve when the drug is withdrawn.

Diagnostic criteria

In 2014, the International Society for Sexual Medicine published an evidence-based unified definition of premature ejaculation that comprised the following criteria[3] :

1. Ejaculation that always or nearly always occurs before, or within about 1 minute of, vaginal penetration from the first sexual experience (lifelong premature ejaculation) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired premature ejaculation)
2. Inability to delay ejaculation on all or nearly all vaginal penetrations
3. Negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy

DSM-5 criteria

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), classifies premature (early) ejaculation as belonging to a group of sexual dysfunction disorders that are typically characterized by a clinically significant inability to respond sexually or to experience sexual pleasure.[4]

Sexual functioning involves a complex interaction among biologic, sociocultural, and psychological factors, and the complexity of this interaction makes it difficult to ascertain the clinical etiology of sexual dysfunction. Before any diagnosis of sexual dysfunction is made, problems that are explained by a nonsexual mental disorder or other stressors must first be addressed. Thus, in addition to the criteria for premature (early) ejaculation, the following must be considered:

• Partner factors (eg, partner sexual problems or health issues)

• Relationship factors (eg, communication problems and differing levels of desire for sexual activity)

• Individual vulnerability factors (eg, history of sexual or emotional abuse, existing psychiatric conditions such as depression, or stressors such as job loss)

• Cultural or religious factors (eg, inhibitions or conflicted attitudes regarding sexuality)

• Medical factors (eg, an existing medical condition or the effects of drugs or medications)

The specific DSM-5 criteria for premature (early) ejaculation are as follows[4] :

• In almost all or all (75-100%) sexual activity, the experience of a pattern of ejaculation occurring during partnered sexual activity within 1 minute after vaginal penetration and before the individual wishes it

• The symptoms above have persisted for at least 6 months

• The symptoms above cause significant distress to the individual

• The dysfunction cannot be better explained by nonsexual mental disorder, a medical condition, the effects of a drug or medication, or severe relationship distress or other significant stressors

The severity of premature (early) ejaculation is specified as follows:

• Mild (occurring within approximately 30 seconds to 1 minute of vaginal penetration)

• Moderate (occurring within approximately 15-30 seconds of vaginal penetration)

• Severe (occurring before sexual activity, at the start of sexual activity, or within approximately 15 seconds of vaginal penetration)

The duration of the dysfunction is specified as follows:

• Lifelong (present since first sexual experience)

• Acquired (developing after a period of relative normal sexual functioning)

In addition, the context in which the dysfunction occurs is specified as follows:

• Generalized (not limited to certain types of stimulation, situations, or partners)

• Situational (limited to specific types of stimulation, situations, or partners)

Premature ejaculation is believed to be a psychological problem and does not represent any known organic disease involving the male reproductive tract or any known lesions in the brain or nervous system. The organ systems directly affected by premature ejaculation include the following[5] :

• Male reproductive tract (ie, penis, prostate, seminal vesicles, testicles, and their appendages)
• Portions of the central and peripheral nervous system controlling the male reproductive tract
• Reproductive organ systems of the sexual partner (if female) that may not be stimulated sufficiently to achieve orgasm ^[6]

Perhaps the most pronounced effect of premature ejaculation, however, is psychological: Both partners are likely to be dissatisfied emotionally and physically by this problem. Attempted pregnancy is a particular concern. If the premature ejaculation is so severe that it happens before commencement of sexual intercourse, conception will not be possible unless artificial insemination is used.

Some have questioned whether premature ejaculation is purely psychological. A number of investigators have found differences in nerve conduction/latency times and hormonal differences in men who experience premature ejaculation compared with individuals who do not. The theory is that some men have hyperexcitability or oversensitivity of their genitalia, which prevents downregulation of their sympathetic pathways and delay of orgasm.

Electroencephalography and neuroimaging studies have detected abnormal spontaneous and evoked brain activation responses to erotic stimuli as well as brain structure changes in premature ejaculation patients. A study by Yang et al using functional magnetic resonance imaging (fMRI) demonstrated that patients with lifelong premature ejaculation have an abnormal brain control network, which may contribute to the reduced central control of rapid ejaculation.[7]

A group of nerves in the lumbar spinal cord has been identified as the possible generator of ejaculation. This nerve site is thought to be linked to excitatory and inhibitory dopamine pathways in the brain, which play significant roles in sexual behavior. While research continues, this knowledge is providing the foundation for possible development of medications specifically targeting delay of ejaculation.[8, 9]  

Other questions have been raised regarding possible biochemical components of premature ejaculation. Testosterone is thought to play a role in the ejaculatory reflex. Higher free and total testosterone levels have been demonstrated in men with premature ejaculation than in men without premature ejaculation.[10]

Research published in a Chinese andrology journal showed that semen from men with premature ejaculation contained significantly less acid phosphatase and alpha-glucosidase than did the semen of control subjects.[11] The researchers concluded that these biochemical parameters may reflect dysfunction of the prostate and epididymis, possibly contributing to premature ejaculation; however, their conclusions have yet to be supported by subsequent studies.

A study by Corona et al found that many men with premature ejaculation have low serum prolactin levels.[12] However, this same study found that men in the lowest quartile of serum prolactin levels who had premature ejaculation also demonstrated associated metabolic syndrome, erectile dysfunction, and anxiety. Thus, whereas biochemical markers (eg, prolactin) may contribute to premature ejaculation, organic and psychological associations (eg, anxiety) suggest that biochemical parameters play only a partial role. Further research is needed.

Psychological factors have been found to contribute greatly to premature ejaculation, beyond merely reducing the time to ejaculation. Whereas patients with premature ejaculation show significantly lower intravaginal ejaculatory latency time (IELT) overall, IELT in those who fit DSM-5 criteria for premature ejaculation overlaps with IELT in patients who do not fit the criteria.[13]

However, whereas a shorter IELT has been the measure of premature ejaculation in many studies, the perception of ejaculation control has been shown to mediate patient or partner satisfaction with sexual intercourse and ejaculation-related distress.[14] Although premature ejaculation probably is not a purely psychological disorder, such associations demonstrate that psychological factors play a significant role in its pathogenesis.

As noted (see Pathophysiology, above), the cause of premature ejaculation is considered psychological, although this has not been definitively confirmed.

One psychological explanation for premature ejaculation is that males are conditioned by societal pressures to reach climax quickly because of fear of discovery when masturbating as teenagers or during early sexual experiences with others. This pattern of rapid attainment of sexual release is difficult to change in marital or long-term relationships. The increasing acknowledgment that female arousal and orgasm require more time than male arousal may lead to increased recognition and definition of premature ejaculation as a problem.

It has been theorized that evolutionary factors are involved. From an evolutionary perspective, it seems logical that males who can ejaculate rapidly might be more likely to fertilize a female than those who require prolonged stimulation to reach climax. The genes of a male who ejaculates rapidly (but not before intromission) would be more likely to be passed on. In some settings, a male who could not complete the fertilization process quickly might be pushed away or killed by a competing male because of his obvious vulnerability during intercourse.

Lifelong premature ejaculation

In patients with lifelong premature ejaculation, in which the male has never experienced sexual relations without also experiencing premature ejaculation, a deep-seated emotional disturbance may be present, and the causes may be multiple.

Sometimes, the behavior is a conditioned response resulting from teen masturbation practices, but it can also result from deep anxiety about sex that relates to traumatic experiences encountered by the patient during development (eg, incest, sexual assault, conflict with one or both parents, or other serious disturbances). In most cases of lifelong premature ejaculation, a primary care physician or a urologist should consult with a psychiatrist, psychologist, or other professional.

Acquired premature ejaculation

With regard to acquired premature ejaculation, some type of performance anxiety is often a major factor.

Performance pressure (ie, fear of failure to satisfy the partner) can arise from various precipitating events. Erectile dysfunction is one of the more common events of this type. Fear that an erection will not last may precipitate premature ejaculation. In such cases, the patient may say that the early climax was the result of being extremely excited by his partner, in an effort to avoid admitting that he was unable to maintain his erection throughout intercourse.

Often, however, the situation is more complex. Erectile dysfunction may not be involved, and the key factor may be, for instance, a belittling attitude on the part of the partner. In addition, a female partner actually may have difficulty achieving climax through intercourse and may require direct clitoral stimulation to experience an orgasm. If she does not communicate this to the male partner (and she may conceal it because of feelings about her own inadequacy), coital satisfaction is unlikely.

Because most physicians are not trained sex therapists, it is important to sort out conflicts in the relationship and then refer couples for counseling to professionals with experience and training in that area. Physicians who have some training or experience in treating premature ejaculation and are comfortable managing the problem may choose to begin treatment. If the patient does not respond favorably or if the physician is uncomfortable with treating the condition, the next step is referral to a sex therapist, psychologist, or psychiatrist.

United States statistics

An estimated 30%-70% of American males experience premature ejaculation. The National Health and Social Life Survey (NHSLS) indicates a prevalence of 30%, which is fairly steady through all adult age categories. (In contrast, erectile dysfunction rises in prevalence with increasing age).

However, various surveys have shown that many men do not report premature ejaculation to their physician, possibly because of embarrassment or a feeling that no treatment is available for the problem. Some men might not even perceive premature ejaculation as a medical problem. Such survey data suggest that the percentage of men who experience premature ejaculation at some point in their lives is almost certainly more than the 30% reported in the NHSLS.

International statistics

Estimates of premature ejaculation in European countries and India mirror the prevalence in the United States.[15] The prevalence in other parts of Asia, Africa, Australia, and elsewhere is unknown.

According to the DSM-5, the estimated prevalence of premature (early) ejaculation is highly variable and depends on the definition being employed.[4] Although more than 20-30% of men aged 8-70 years report being concerned about the rapidity of their ejaculation, only 1-3% would be classified as having premature (early) ejaculation according to the current DSM-5 criteria (ie, ejaculation occurring within 1 minute after intromission and before the individual wishes).

In a Korean study, the definition of premature ejaculation used yielded marked differences in outcome. The prevalence of premature ejaculation was 19.5% by self-reporting, 11.3% based on a premature ejaculation diagnostic tool (PEDT) score of 11 or higher, and 3% based on stopwatch-recorded intravaginal ejaculation latency time.[16]

Age- and race-related demographics

Premature ejaculation can occur at virtually any age in an adult man’s life. As a reported condition, it is most common in men aged 18-30 years but may also occur in conjunction with secondary impotence in men aged 45-65 years.

At present, there are no reproducible data indicating major differences between racial groups with respect to the incidence or prevalence of premature ejaculation. However, a few surveys suggest that some degree of racial variation may exist.

A telephone survey of 1320 men without erectile dysfunction by Carson et al found that premature ejaculation was reported by 21% of non-Hispanic African Americans, 29% of Hispanics, and 16% of non-Hispanic whites. An analysis of the NHSLS by Laumann et al found that premature ejaculation was more prevalent among African American men (34%) and white men (29%) than among Hispanic men (27%).[17]

In a small study of a sexual health clinic in Australia, 59% of premature ejaculation diagnoses were in men of Asian or Middle Eastern descent, whereas 41% were in men of Western or European birth.[18] However, in view of the small number of such studies and the lack of suitable control subjects, it is difficult to draw firm conclusions from these data.

Masters and Johnson maintain that the great majority (>85%) of men with premature ejaculation can be treated successfully with the squeeze-pause technique alone, typically within 3 months of the start of therapy.[2] However, clinical experience varies widely, and some authors have reported much poorer success rates.

With a combination of methods, including selective serotonin reuptake inhibitor (SSRI) therapy, improvement or cure should be possible in most cases, provided that the couple (not just the man) is committed to working on the problem together. Numerous published reports also indicate that counseling and medical therapy can help achieve success rates as high as 85%, matching the high rates originally reported by Masters and Johnson.

The problem with all treatments for premature ejaculation is that the relapse rate ranges from 20% to 50%, depending on the study cited; thus, the durability of the response can be questionable. Some males may need to make a long-term commitment to periodically repeating the behavioral techniques; long-standing habits can be difficult to modify.

Some men who achieve success with medical therapy (ie, SSRIs) might need to use the medication for the rest of their lives, just as some people with depression need lifelong antidepressant therapy to prevent repeated bouts of the disorder and many people with hypertension need lifelong antihypertensive therapy to control their blood pressure. Precise long-term failure rates are not well established and depend on the duration of follow-up for a particular cohort of patients.

No known direct morbidity or mortality results from premature ejaculation. Indirectly, premature ejaculation may alter self-esteem, may cause marital dysfunction, and may be a factor in depression, with its obvious consequences. Severe premature ejaculation can cause stress within a marriage or other relationship, which might contribute to conflicts and separation or divorce in some cases. Conception is also difficult in cases of premature ejaculation before vaginal intromission.

Patients with premature ejaculation may be referred to a licensed sex therapist, psychologist, psychiatrist, or marital counselor for additional help. Numerous books and articles in the lay press are available at any public library. Many can also find information on the Internet regarding this subject.

Future research might indicate whether better sex education during adolescence can decrease the incidence of premature ejaculation in young men. Early successful treatment of erectile dysfunction may help prevent acquired premature ejaculation in older men.

For patient education resources, see the Men’s Health Center, as well as Premature Ejaculation, Impotence/Erectile Dysfunction, Erectile Dysfunction FAQs, Nonsurgical Treatment of Erectile Dysfunction, and Erectile Dysfunction Medications.

A guideline from the International Society of Sexual Medicine recommends asking patients the following questions to establish the diagnosis of premature ejaculation[19] :

• What is the time between penetration and ejaculation (cumming)?
• Can you delay ejaculation?
• Do you feel bothered, annoyed, and/or frustrated by your premature ejaculation?

Optional questions cover assessment of erectile function, impact of the problem on the patient's relationship with his partner, any previous treatment, and effect on quality of life.[19]

The history of the patient’s premature (early) ejaculation is helpful because it ultimately guides the treatment that is best suited to the patient (and his partner). One should determine whether premature ejaculation is lifelong (ie, primary) or acquired (ie, secondary) and assess the severity of the problem.

If the patient has always experienced premature ejaculation from the time he began coitus, then he has lifelong premature ejaculation. If he had successful coital relationships in the past, yet began experiencing premature ejaculation with the current relationship, then he has acquired premature ejaculation. In most cases, acquired premature ejaculation is easier to treat and has a better prognosis.

For completeness, a general medical history should be taken to screen for other medical conditions that might be relevant. For example, if the patient has angina with subsequent fear of myocardial infarction during sexual activity, he may present with premature ejaculation, but the actual underlying problem is the cardiac disease and the attendant mental insecurity. Resolution of the cardiac problem usually suffices, with no specific therapy required for the premature ejaculation.

For the purposes of this discussion, it is assumed that the patient is healthy and that sexual dysfunction is the only significant problem.

Lifelong premature ejaculation

In addition to the general medical history, it is important to inquire about any previous psychological difficulties. Psychiatric conditions are more common in males with lifelong premature ejaculation than in the general population.

The history should include questions about the following:

• Early sexual experiences – Did the patient experience a traumatic sexual episode as a child or teenager (eg, discovery by a parent during masturbation, with subsequent feelings of guilt and perhaps threatened or actual punishment)?

• Family relationships during childhood and adolescence – How did the patient relate to his mother, father, brother(s), sister(s)? Does the family have a history of incest or sexual assault? Males can be sexually assaulted by other males and, in rare instances, by females, including siblings

• Peer relationships – Did the patient have other male friends or any female friends? How does he regard himself in comparison with peers (eg, inferior, superior, more athletic, frailer, more intelligent, or less intelligent)?

• Work or school – Does the patient have any difficulties with work (or school, if still a student)?

• General attitude toward sex – Does the patient regard sex as dirty? What is his sexual preference, fantasy, and arousal pattern? Did the patient have a strict religious upbringing? If so, what was he taught about sex?

• Marital versus nonmarital context – If the premature ejaculation began with an initial nonmarital relationship, does he feel guilt about this? If the first coital experience was within a marital relationship that involved premature ejaculation from the start, was there premarital noncoital sexual play between the partners?

• Sexual attitude and response of the female partner – If the female partner is having a problem (eg, dyspareunia), it could relate to the male’s problem or may have preceded it

• Nonsexual aspects of the current relationship – Does the couple fight, or are they going through a power struggle?

• Involvement of the sexual partner – If the patient’s sexual partner is not present for this interview, why not? Is the partner failing to support the man or blaming him?

Clues from these and similar questions usually point toward causative factors that may be specifically addressed with therapy.

Acquired premature ejaculation

In addition to a general medical history, the history should include details about the following:

• Previous relationships – Were there earlier relationships in which premature ejaculation was not a problem? Were there earlier relationships in which transient episodes of premature ejaculation occurred?

• Current relationship – Was premature ejaculation always a problem, or did it start after an initial time frame when coitus was satisfactory to both partners?

• Nonsexual aspects of the current relationship – Do the partners get along on most issues, or is conflict present? Who is dominant in the relationship, or is the relationship generally equal?

• Involvement of the sexual partner – If the patient’s female sexual partner did not accompany him to the clinic, why not? If she regards the problem as his alone, rather than theirs, this may be an important clue

• Impotence problems – If the patient has erectile dysfunction, did it begin after the premature ejaculation or before? If the patient does not have erectile dysfunction, what is the general timing for the male (ie, the typical time from commencement of intromission to climax)?

• Capacity for coitus – Can actual coitus be achieved, or does the premature ejaculation prevent it entirely?

• Sexual context – Is the patient experiencing premature ejaculation with self-stimulation (ie, masturbation), with nonintercourse stimulation by the partner, or just with coitus?

• Sexual response of partner – What is the time required for the female partner to reach climax? Can she reach climax with intercourse, or does she require direct clitoral stimulation (oral or manual)?

If the patient has erectile dysfunction that began after premature ejaculation, treatment of both conditions may be required; in some cases, the erectile difficulty resolves once the patient gains confidence in his ability to control ejaculation. If erectile dysfunction developed first, premature ejaculation may be a secondary sexual dysfunction; it may resolve when the patient is confident of being able to maintain his erection.

Physical examination findings are normal in males whose only presenting condition is premature ejaculation. If other relevant medical conditions are present, signs of these conditions will be noted.

In males with premature (early) ejaculation and no other medical problems, no specific conventional laboratory tests aid or affect treatment. If premature ejaculation is observed in conjunction with an impotence problem, it may be appropriate to check the serum testosterone (free and total) level and the prolactin level. If depression or other conditions are coexisting with premature ejaculation, laboratory studies specific to depression or to another medical or psychological problem are warranted. Premature ejaculation has been linked to hyperthyroidism, so measurement of thyroid-stimulating hormone may be considered in patients with signs or symptoms suggesting hyperthyroidism[22] .

Some investigators are performing vibrational threshold testing on volunteer subjects; others are using nerve conduction times, somatosensory latency testing, or both. A few investigators are evaluating the hypothalamic-pituitary-gonadal axis, some are testing melatonin levels, and some are measuring levels of carbon monoxide and nitric oxide (mediators of male sexual function). At present, however, all such determinations must be considered experimental; none have yet proved to be applicable to current clinical practice.

Medical treatment for premature (early) ejaculation includes several options. Any serious primary medical condition (eg, angina) should be treated; for the purposes of the following discussion, the patient is assumed to be healthy, and premature ejaculation is assumed to be his only problem. In addition, any accompanying erection problem (eg, erectile dysfunction [ED]) should be treated; various methods are available, and excellent success can be expected. Accordingly, treatment of concomitant ED is mentioned only in passing.[23]

To achieve the best outcome, the female partner should be included as fully as possible in the treatment and counseling sessions. Pharmacologic therapy may include selective serotonin reuptake inhibitors (SSRIs) or topical desensitizing agents.

Outpatient care can be scheduled as appropriate for the clinical circumstances.

To date, no drug has been specifically approved by the US Food and Drug Administration (FDA) for the treatment of premature ejaculation. However, numerous studies have shown that selective serotonin reuptake inhibitors (SSRIs) and drugs with SSRI-like side effects are safe and effective to treat this condition, and many physicians use these agents for this purpose. Topical desensitizing therapy with local anesthetic agents can also be useful in some men with premature ejaculation.

Premature ejaculation that relates to erectile dysfunction may resolve if the erectile dysfunction is treated successfully. If a patient has depression-related erectile dysfunction but not premature ejaculation, a drug with minimal adverse sexual effects might be considered so as to avoid causing delayed ejaculation or even anorgasmia.[24] However, if the patient has premature ejaculation, erectile dysfunction, and depression, an antidepressant with SSRI side effects has the added benefit of possibly alleviating the premature ejaculation.[25]

Desensitizing agents

In Korea and other areas of the Far East, SS (Super Secret) cream (a combination of 9 ingredients, mainly herbal) has been shown to desensitize the penis, decrease the vibratory threshold, and help men with premature ejaculation to delay their ejaculatory response significantly.[26, 27]  This preparation is not yet approved by the FDA.

Simple combinations of lidocaine cream or related topical anesthetic agents can also be effective. These combinations are safe as long as the patient has no history of allergy to the substance.[28, 29, 30, 31]  A metered-dose lidocaine-prilocaine cutaneous spray (Fortacin) is approved in Europe.[32]

Selective serotonin reuptake inhibitors and similar agents

The most effective pharmacologic therapy for premature ejaculation is to administer a drug from the SSRI class. Normally, these drugs are used as antidepressants in the clinical setting. Many of these agents were found to have the side effect of significantly delaying the achievement of orgasm in both male and female patients, and it was for this reason that such agents were applied to the treatment of premature ejaculation.

Some tricyclic antidepressants (TCAs) with SSRI-like activity have the same effect in orgasm that SSRIs do. The TCA that has been most frequently studied for treatment of premature ejaculation is clomipramine.[33, 34, 35, 36] Many investigators find that clomipramine is more effective for premature ejaculation than many SSRIs are. Results of a multicenter, randomized, double-blind, placebo-controlled, fixed-dose clinical phase III study in 159 Korean patients suggest that 15 mg of clomipramine taken approximately 2-6 hours before sexual intercourse is effective and safe for treatment of premature ejaculation.[37] However, a systematic review and meta-analysis concluded that below a dose of 50 mg, a higher dose of clomipramine results in a longer delay of ejaculation without an increased risk of adverse events.[38]

In most cases, females require considerably more time to reach climax than males do; thus, in females taking  SSRIs and SSRI-like agents, the delayed climax caused by these agents becomes an adverse effect. In many females, such an inability to reach orgasm can induce a pattern of sexual avoidance, along with a corresponding decrease in libido or sexual excitement (lubrication). In males, too-rapid orgasm can cause some of the same patterns of sexual avoidance and decreased libido. Thus, it is essential to determine the primary problem when instituting therapy.

SSRIs useful for treating premature ejaculation include the following:

• Sertraline ^[39]
• Paroxetine
• Fluoxetine
• Citalopram
• Dapoxetine

Dapoxetine, which is generally categorized as a fast-acting SSRI, was developed specifically to treat this condition. It may be effective at the first dose (ie, on demand) when given 1-3 hours before sexual intercourse, and its adverse-effect profile is comparable to those of other SSRIs.[40, 41, 42] Dapoxetine has been approved in a number of countries but not yet in the United States. In a study of men with both premature ejaculation and erectile dysfunction who were on phosphodiesterase type 5 (PDE5) therapy, dapoxetine provided treatment benefit and was generally well tolerated.[43]  However, up to 90% of patients discontinue dapoxetine, mostly because of adverse effects, cost, and disappointing efficacy.[32]

The optimal medical treatment regimen for premature ejaculation has not been established. The author’s experience has been that in some males, single dosing before sexual relations can work well, whereas in others, it may be necessary to achieve and maintain a target blood level through daily use of the medication, as in the treatment of clinical depression.

Obviously, if single dosing is successful, therapy is simpler and has fewer adverse effects. Accordingly, this may be the preferred initial approach. If necessary, the dose may be increased in a stepwise fashion until a therapeutic effect is achieved or the maximum daily recommended dose is reached. No exact schedule for increasing the dose has been established; the experience of the physician, the response of the patient, the adverse effects experienced by the patient, and other general medical considerations should be the guiding factors.

If the initial SSRI fails to help the patient, it is certainly reasonable to try a second agent. However, if the second choice fails, it is not likely that a third choice will offer any benefit. As with treatment for depression, if a patient has been taking the maximal dose of the medication for 6 weeks without showing any improvement, the likelihood that a more prolonged course of therapy with a particular drug would be successful is remote.

There is no reason why pharmacotherapy cannot be combined with behavioral modification therapy, desensitizing creams, or both; the use of several simultaneous treatments can result in additive effects or even synergy. If all treatment fails, then the patient’s only options are as follows:

• To see a different health care professional, if he wishes
• To accept his condition as being untreatable with currently available therapeutic options

Adverse effects of long-term SSRI use are a significant concern and should be considered by both the physician and the patient.[44] Such adverse effects may include the following:

• Psychiatric and neurologic sequelae
• Dermatologic reactions
• Anticholinergic effects
• Fluctuation in body weight
• Cognitive impairment
• Drug interactions
• Sexual side effects other than delayed ejaculation (eg, erectile dysfunction or loss of libido)

In addition, caution should be exercised in changing SSRIs; a washout period is necessary to avoid overdose. SSRI discontinuance syndrome (especially with paroxetine) has been associated with dose reduction or discontinuance and may cause dizziness, nausea and vomiting, headache, gait instability, lethargy, agitation, anxiety, and insomnia.[45]

Phosphodiesterase type 5 inhibitors

Some studies have demonstrated that combining phosphodiesterase type 5 (PDE5) inhibitors with SSRIs provides better results in the treatment of premature ejaculation than using SSRIs alone.[46] The reason for this is unknown, but part of the explanation may be that the improved (firmer, longer-lasting, or both) erection resulting from the PDE5 inhibitor provides inhibition of ejaculation via downregulation of receptors involved in somatosensory latency times. In addition, a reduction in performance anxiety may exist on a subconscious level.

Regardless of the mechanism, PDE5 inhibitors have been found to be safe and effective as a therapeutic adjunct for premature ejaculation in men for whom such therapy is not otherwise contraindicated. The only PDE5 inhibitors studied to any significant degree in the setting of premature ejaculation are sildenafil and tadalafil[47, 48] ; vardenafil may also work, but the available data are insufficient to support its use.

A single-blind randomized placebo-controlled clinical study in 100 patients concluded that tadalafil, 5 mg once daily for 6 weeks, was significantly more effective than placebo (P=0.001) and was well tolerated in the treatment of premature ejaculation.[49] Similarly, a meta-analysis of 15 randomized clinical trials suggests that PDE5-Is are significantly more effective than placebo (231 participants; P <  0.00001), that there is no difference between PDE5-Is and selective serotonin reuptake inhibitors (SSRIs; 405 participants, P = 0.50), and that PDE5-Is combined with an SSRI are significantly more effective than SSRIs alone (521 participants, P = 0.001).[50] The use of PDE5 inhibitors for the treatment of premature ejaculation is not approved by the FDA and is considered an off-label use.

Other agents

A study by Safarinejad demonstrated that a single daily high dose of pindolol (a nonselective beta-adrenergic antagonist with 5-HT1A autoreceptor antagonist properties[51] ) in combination with paroxetine (or possibly another SSRI) delayed ejaculation in patients in whom paroxetine therapy alone failed to provide benefit.[52] However, more studies must be performed before pindolol can be considered an ideal option for first- or second-line treatment of premature ejaculation.

In studies by Safarinejad and Hosseini[53] and Salem et al,[54] the opioid analgesic tramadol was found to be significantly more effective than placebo in terms of increased time to ejaculation, increased sexual intercourse satisfaction, and tolerability. In a randomized double-blind, placebo-controlled clinical trial by Hamidi-Madani et al in 150 patients, 12 weeks of tramadol 50 mg on demand, paroxetine 20 mg on demand, and placebo all resulted in improvement, but the tramadol group experienced significantly greater benefit than the paroxetine and placebo groups (P < 0.0001).[55]

A systematic review and meta-analysis found that tramadol may be effective in treatment of premature ejaculation, especially when other therapies have failed, but that it remains necessary to consider the possibility of drug addiction and adverse effects before initial use or after long-term use.[56] A meta-analysis of on-demand use of tramadol noted that the available evidence was of low to moderate quality, but the drug appears to be effective in this setting, with a low rate of adverse events; the effective dose remains uncertain, but some data support the use of 50 mg.[57]

The first step is to attempt to relieve any underlying performance pressure on the male. If premature ejaculation occurs when intercourse is attempted, the couple should be instructed not to attempt intercourse until the ejaculatory problem is treated. In the meantime, the male may use manual stimulation, oral sex, or other means to satisfy the female partner.

If the male always experiences ejaculation with initial sexual excitement or early foreplay, this is a serious problem and probably indicates lifelong premature ejaculation (the history should reveal this). Such cases will most likely call for treatment in conjunction with a mental health care professional. These more difficult cases should be screened out.

Next, the couple should be instructed in sex therapy techniques, such as the stop-start or squeeze-pause technique popularized by Masters and Johnson.[2]

In this technique, the female partner slowly begins stimulation of the male but stops as soon as he senses a feeling of excessive excitement that may lead to ejaculatory inevitability. She then administers firm compression to the penis just behind the glans, pressing mainly on the underside. This compression should be uncomfortable but not painful. Once the male has the feeling that ejaculation is no longer imminent, the female resumes stimulation.

The process should be repeated and practiced at least 10 or more times. Over time, most males find that this technique helps decrease the impending inevitable need to ejaculate.

After practicing this technique for a while, the couple can move to another phase of the process. In this phase, the partners sit facing each other, with the woman’s legs crossing on top of the male’s legs. She stimulates him by manipulating his penis first close to and then with friction against her vulval area. Each time he senses excessive excitement, she applies the squeeze and stops all stimulation until he calms down enough for the process to be repeated.

Finally, coitus may be attempted, with the female partner in the superior position so that she may withdraw immediately and again apply a squeeze to remove the male partner’s urge to climax.

Most couples find this technique to be highly successful. It can also help the female partner to be more aroused and can shorten her time to climax because it constitutes a form of extended foreplay in many cases.

Other nonpharmacologic approaches may be helpful. If the male is relatively young and can achieve another erection within a few minutes after a premature ejaculation, he may find that he is much less likely to experience a premature ejaculation the second time. The interval for achieving a second climax often includes a much longer period of latency, and the male can usually exert better control in this setting.

Accordingly, some therapists advise young men to masturbate (or have their partner stimulate them rapidly to climax) 1-2 hours before sexual relations are planned. In an older man, such a strategy may be less effective, because the older man may have difficulty achieving a second erection after his first rapid sexual release. If this occurs, it can damage his confidence and may result in secondary impotence.

Kilinc et al reported that moderate physical activity longer than 30 min at least 5 times a week leads to ejaculation delay in patients with premature ejaculation. In their study, 35 patients were treated with dapoxetine, 30 mg on demand; 35 performed moderate physical activities; and 35 performed minimal physical activity..[58]

Pastore et al reported long-term benefit from pelvic muscle floor rehabilitation (PFM) in patients with lifelong premature ejaculation. The 154 participants in this retrospective study entered a 12-week program of PFM rehabilitation, including physio-kinesiotherapy treatment, electrostimulation, and biofeedback, with three sessions per week, with 20 min for each component completed at each session. Of the 122 participants who completed PFM rehabilitation, 111 gained control of their ejaculation reflex. Of the 95 participants who completed follow-up, 64% maintained satisfactory ejaculation control at 24 months and 56% did so at 36 months.[59]

No recommended surgical treatment exists for premature ejaculation.

Before the availability of nonsurgical methods for treating erectile dysfunction, a patient with premature ejaculation who was mistakenly diagnosed with erectile dysfunction might have undergone a penile prosthesis implantation, which would have yielded unsatisfactory results because of the incorrect initial diagnosis. In this scenario, the patient would be able to engage in sexual intercourse, because the penile implant would provide an adequate erection, but he would still climax prematurely.

Currently, penile implants are placed much more rarely, and with the use of nonsurgical treatments for erectile dysfunction, any permanent harm resulting from diagnosing erectile dysfunction rather than premature ejaculation is unlikely.

Consultation with a sex therapist, psychologist, or psychiatrist may prove helpful if the primary care physician or urologist cannot provide successful treatment or does not have the time to explore psychological issues and implement behavioral techniques (eg, squeeze-pause). If the primary care physician or urologist is inexperienced or uncomfortable with treating premature ejaculation, early referral to a sex therapist, psychologist, or psychiatrist is indicated.

Some physicians are comfortable implementing pharmacologic therapy but not behavioral therapy. As with any medical condition, the patient should be offered all available treatment options, and the physician should proceed with referral for any option considered to require more specialized help than the physician can provide.

For men who may have a severe emotional disturbance underlying the premature ejaculation, referral to a mental health professional is most appropriate. Diagnosis and treatment of the various psychological factors that manifest partly as premature ejaculation are beyond the scope of this discussion.

International Society of Sexual Medicine

The International Society of Sexual Medicine (ISSM) has developed evidence-based guidelines for patients suffering from lifelong premature ejaculation (PE), which include definitions of lifelong and acquired PE; discussions of the epidemiology, etiology, diagnosis, and treatment of PE; and a flow chart for the management of PE. The guidelines were most recently reviewed and revised in 2013.[60]

American Urologic Association

The American Urologic Association (AUA) published guidelines on the pharmacologic management of PE in 2004; the guidelines were reviewed and validated in 2010.[61] Guideline statements were as follows:

• The diagnosis of PE is based on sexual history. A detailed sexual history should be obtained from all patients with ejaculatory complaints.
• In patients with concomitant PE and erectile dysfunction (ED), the ED should be treated first.
• Before initiating any intervention, clinicians should discuss the risks and benefits of all treatment options. Patient and partner satisfaction is the primary target outcome for the treatment of PE.
• Any of several serotonin reuptake inhibitors or topical anesthetics can provide effective treatment for PE. The optimal treatment choice should be based on both physician judgment and patient preference.

The AUA also noted the following:

• Although not approved by the US Food & Drug Administration for treatment of PE, oral antidepressants and topical anesthetic agents are effective and have minimal side effects when used for this purpose.
• 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.

Italian Society of Andrology and Sexual Medicine

The Italian Society of Andrology and Sexual Medicine (SIAMS) issued guidelines on the management of PE in 2020.[22] In addition to recommendations regarding definitions and diagnosis, SIAMS recommends use of the following medications, which are approved in Europe for treatment of PE:

• Dapoxetine as first-line on-demand oral therapy for both lifelong and acquired PE; the suggested starting dose is 30 mg, ingested with a full glass of water 1–3 h before intercourse, with no titration to 60 mg or addition of other treatment until after at least 6–8 full sexual attempts in a congruous erotic environment
• Eutectic lidocaine/prilocaine spray as local therapy for lifelong PE

SIAMS recommendations regarding off-label therapy include the following:

• Obtain written and signed informed consent before initiating off-label treatment.
• Use dapoxetine and a phosphodiesterase type 5 (PDE5) inhibitor to improve ejaculatory control in patients with comorbid erectile dysfunction (ED) and PE (loss of control of erection and ejaculation [LCEE]).

• Consider the combination of dapoxetine and lidocaine/prilocaine in patients with PE refractory to a single therapy.

• Use a PDE5 inhibitor in patients with ED or subclinical ED and PE (LCEE).

• Consider on-demand use of a selective serotonin reuptake inhibitor (SSRI; ie, paroxetine or fluoxetine) for PE refractory to first-line treatments and in the absence of psychiatric contraindications, as confirmed by a psychiatric consultation and psychometry.

• Consider daily use of clomipramine or an SSRI (paroxetine or fluoxetine) for PE refractory to first line-treatments or to on-demand SSRI use, in the absence of psychiatric contraindications, as confirmed by a psychiatric consultation and psychometry.

SIAMS recommends against the following:

• Prescription of an antidepressant without a careful screening for depression and determination of the endogenous or reactive nature of the depression
• Use of alpha-1 adrenergic receptor blockers as second-line therapy in men with PE/lower urinary tract symptoms (LUTS)
• Use of tramadol for PE

No drug is specifically approved by the US Food and Drug Administration (FDA) for the treatment of premature (early) ejaculation. However, various agents have been safely and effectively used for this purpose. Selective serotonin reuptake inhibitors (SSRIs) and antidepressants with SSRI-like effects have been the most successful. Desensitizing creams containing local anesthetics can also be useful in some cases; though not FDA-approved, they are believed to be of at least some efficacy and carry minimal risk.

Premature ejaculation that relates to erectile dysfunction may resolve if the erectile difficulty is treated successfully. Drugs for the treatment of erectile dysfunction include sildenafil, vardenafil, tadalafil, alprostadil, and, possibly, an SSRI (if depression is causing the erectile dysfunction).

Class Summary

The mechanism of action of SSRIs is linked to their inhibition of neuronal uptake of serotonin (5-HT) in the central nervous system (CNS).

Various animal studies suggest that SSRIs have weak effects on norepinephrine and dopamine neuronal reuptake. They do not antagonize adrenergic (eg, alpha1 -adrenergic, alpha2 -adrenergic, or beta-adrenergic), cholinergic, GABAergic, dopaminergic, histaminergic, serotonergic (5-HT1A, 5-HT1B, or 5-HT2), or benzodiazepine receptors; therefore, they have fewer adverse anticholinergic effects than tricyclic antidepressants (TCAs) do.

Adverse effects of long-term SSRI use are a significant concern and should be considered by both the physician and the patient. These adverse effects include psychiatric and neurologic sequelae, dermatologic reactions, anticholinergic effects, fluctuation in body weight, cognitive impairment, drug interactions, and sexual side effects other than delayed ejaculation (eg, erectile dysfunction or loss of libido.

Paroxetine (Paxil, Pexeva)

Paroxetine is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.

Sertraline (Zoloft)

Sertraline is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.

Citalopram (Celexa)

Citalopram is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.

Fluoxetine (Prozac)

Fluoxetine is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.

Class Summary

Drugs with SSRI-like side effects (eg, delaying sexual climax), such as certain TCAs, can be used to treat premature ejaculation. The TCA most studied for treatment of premature ejaculation is clomipramine, which may be more effective than many SSRIs for this purpose.

Clomipramine (Anafranil)

Clomipramine inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. These actions are believed to be responsible for its antidepressant activity. Inhibition of serotonin probably gives rise to the SSRI-like activity that produces side effects (eg, inhibition of ejaculation).

Class Summary

Topical anesthetics may reduce penile sensitivity and excitability and delay ejaculation. Topical anesthetic cream is probably the lowest-risk medication that can be used for premature ejaculation; it has no adverse systemic effects, in the absence of prior hypersensitivity to the medication on the part of the patient or his partner. As a rule, there is no contraindication for combined therapy with topical anesthetics, antidepressants, and behavioral therapy.

Lidocaine 2.5% and prilocaine 2.5% (EMLA)

Lidocaine and prilocaine are amide-type local anesthetic agents. Both agents stabilize neuronal membranes by inhibiting the flow of certain ions required for the initiation and conduction of nerve impulses, thus producing local anesthesia. Lidocaine and prilocaine are applied to intact skin under an occlusive dressing, providing dermal analgesia. The effectiveness of this approach when it is applied to the penis is unproved; an occlusive dressing might also be difficult unless the penis is covered with a condom or cellophane.

Class Summary

In some studies, sildenafil and other phosphodiesterase type 5 (PDE5) inhibitors in combination with SSRIs has yield better results in treating premature ejaculation than SSRIs alone. The mechanism of this effect is unknown. Regardless of the mechanism, PDE5 inhibitors are safe and effective treatment adjuncts for premature ejaculation if not otherwise contraindicated. The only PDE5 inhibitors studied to any degree in this setting are sildenafil and tadalafil; vardenafil may also work, but more data are needed.

Sildenafil (Viagra)

Sildenafil is FDA-approved for the treatment of erectile dysfunction but not specifically for the treatment of premature ejaculation. If both conditions are present, sildenafil may help them both. Sildenafil in combination with an SSRI-type drug alleviates premature ejaculation better than an SSRI-type drug alone, as measured by prolongation of intravaginal ejaculatory latency time (IELT). More drug-related adverse events may occur because 2 medications are being used rather than just 1.

Tadalafil (Cialis)

Tadalafil is FDA-approved for the treatment of erectile dysfunction but not specifically for the treatment of premature ejaculation. Studies suggest that it may improve both conditions concurrently. Tadalafil in combination with an SSRI-type drug alleviates premature ejaculation better than an SSRI-type drug alone, as measured by prolongation of IELT. More drug-related adverse events may occur because 2 medications are being used rather than just 1.

Inhibition of PDE5 increases cyclic guanosine monophosphate (cGMP) activity, which increases the vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Increased sensitivity for erections may last 36 hours with intermittent dosing. For more frequent sexual activity (eg, twice weekly), a daily low-dose regimen may be recommended; men can attempt sexual activity at any time between daily doses. Tadalafil is available as 2.5-mg, 5-mg, 10-mg, and 20-mg tablets.

Class Summary

Pindolol is a nonselective beta-adrenergic antagonist that has been shown to have 5-HT1A autoreceptor antagonist properties in the dorsal raphe nuclei. It is hypothesized that this 5-HT1A autoreceptor antagonism increases the synaptic content of 5-HT and subsequently potentiates the action of an SSRI medication. More studies are required before pindolol can be considered an ideal option for first- or second-line treatment of premature ejaculation.

Pindolol

Pindolol is a nonselective beta-adrenergic antagonist used in combination with paroxetine for premature ejaculation refractory to paroxetine alone. This is an off-label use of pindolol.

Class Summary

Tramadol is an analgesic with centrally acting opioid activity (weak μ-opioid effect) in addition to inhibition of reuptake of 5-HT and norepinephrine. It is hypothesized that the increased synaptic content of serotonin and norepinephrine at the level of the spinal cord and peripheral sensory nerves provides the mechanism for effective treatment of premature ejaculation.

Tramadol (Ultram, Rybix ODT, ConZip, Ryzolt)

Tramadol is a centrally acting opioid analgesic that exerts its effect by combining opioid receptor activation with inhibition of norepinephrine and serotonin reuptake. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment. Treatment of premature ejaculation is an off-label use of tramadol.