Approach Considerations
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.
Pharmacologic Therapy
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
A systematic review and meta-analysis reported that although fluoxetine was more effective than placebo in treating PE, sertraline and paroxetine were more effective than fluoxetine (p < 0.05). [40]
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. [41, 42, 43] 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. [44] 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. [45] 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. [46]
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. [47] 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 [48, 49] ; 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. [50] 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). [51] 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 [52] ) in combination with paroxetine (or possibly another SSRI) delayed ejaculation in patients in whom paroxetine therapy alone failed to provide benefit. [53] 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 [54] and Salem et al, [55] 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). [56]
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. [57] 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. [58]
Counseling and Sex Therapy
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.
Other Therapy
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.. [59]
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. [60]
Surgical Intervention
Surgical procedures that reduce penile sensation have been proposed as treatments for premature ejaculation. These include selective dorsal nerve neurotomy, pulsed radiofrequency ablation or cryoablation of dorsal penile nerves, and hyaluronic acid gelaugmentation of the glans penis. [61, 62] Currently, all those are considered experimental. [61]
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.
Consultations
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.
