1 .Medical history (recommended)
1) History of sexual life
Triggers, frequency, occurrence and duration of premature ejaculation.
Ability to control ejaculation.
The latency of intravaginal ejaculation.
environmental factors, intensity of sexual stimulation and the situation of sexual partners in which premature ejaculation occurs.
The emotional situation of the parties to the sexual act.
the characteristics and frequency of sexual intercourse.
The situation of ejaculation and orgasm.
the progression and evolution of premature ejaculation
The impact of premature ejaculation on the psychological factors and quality of life of both parties to the sexual act.
Whether combined with other sexual dysfunction diseases.
2.General medical history
Health status.
Educational background.
History of cardiovascular diseases.
History of endocrine disorders.
History of neurological disorders.
History of genitourinary disorders.
History of trauma.
History of surgery.
History of drug application.
History of psychological disorders and treatment.
Psychosexual status.
History of other systemic diseases.
For primary premature ejaculation.
Family or genetic history; growth and life history; history of trauma; psychosexuality and sexual orientation.
2. Intravaginal ejaculatory latency (recommended)
Intravaginal ejaculation latency is an important indicator that can be measured to evaluate premature ejaculation and is widely used in the diagnosis of premature ejaculation and clinical research. However, its application alone is not sufficient for the diagnosis of premature ejaculation because the temporal overlap of intravaginal ejaculatory latency in premature and non-premature men is too great [1], and on the other hand, the artificial determination of intravaginal ejaculatory latency produces a significant direct effect on the sense of self-control of ejaculation, but not on ejaculation-related psychological behavior [2]. In clinical practice, intravaginal ejaculatory latency alone has 80% specificity and 80% sensitivity for diagnosing premature ejaculation [3], and its specificity can reach 96% if one of control of ejaculation, satisfaction with sexual behavior and resulting psychological distress and interpersonal disturbances is also added [4].
3. Premature ejaculation assessment questionnaire (optional)
Questionnaires based on patient-reported outcomes should be applied to evaluate premature ejaculation and to identify and diagnose patients with premature ejaculation accordingly. These questionnaires mainly include the Premature Ejaculation Diagnostic Tool [5], the Arab Premature Ejaculation Index [6] and the Chinese Premature Ejaculation Questionnaire [7].
1, Premature ejaculation diagnostic tool evaluates ejaculatory control, frequency of premature ejaculation, psychological distress and interpersonal difficulties.
2, The Arab Premature Ejaculation Index evaluates sexual desire, firm erection to complete full intercourse, time to ejaculation, ejaculatory control, patient and partner satisfaction, and anxiety or depression.
3. Chinese premature ejaculation questionnaire
Other scales expressing the characteristics of premature ejaculation and determining its efficacy include the Premature Ejaculation Spectrum [8] and the Premature Ejaculation Index [9]. (Tables 4,5)
4, Premature ejaculation examination
1) Physical examination
(a) Genital examination (optional): penis, testes, epididymis, prostate, male secondary sexual characteristics
b) Neurological examination (not recommended): testicular reflex, bulbocavernosal reflex, anal sphincter tension
2) Laboratory tests (not recommended): prostatic fluid routine, semen routine, endocrine hormone test, and endocrine hormone test.
3) Special auxiliary examinations (not recommended)
a) Neurophysiological examination: dorsal nerve sensory evoked potentials, neuromyography
b) Autonomic nerve function examination
c) penile vascular examination
d) cystoscopy
e)transrectal ultrasonography
f)urinary flow rate examination
g)erectile function examination
h)penile vibration stimulation test
4)Psychosexual and related psychological disease assessment of patient and spouse (optional)
5. Diagnostic process of premature ejaculation
IELT≥1min
Premature ejaculation-like ejaculation disorder
Diagnosis of premature ejaculation
Whether combined with
other sexual dysfunction
Yes
Diagnosis after treatment of comorbidities
No
Primary premature ejaculation
Normal idiosyncratic presentation
IELT <1min
Medical history inquiry
Intravaginal ejaculation latency
Degree of ejaculatory self-control
Level of patient or partner stress
Onset and duration of premature ejaculation
History of psychological disorders
General disease history
Physical and ancillary examinations
Secondary premature ejaculation
6. Evidence-based level of premature ejaculation diagnosis and level of recommendation
Recommendation
Evidence level classification
Level of recommendation
Medical and sexual history.
Comprehensive evaluation of intravaginal ejaculatory latency, sense of self-control, psychological distress, interpersonal difficulties, and ejaculatory dysfunction.
1a
A
Determination of intravaginal ejaculatory latency
2a
B
Patient-reported outcomes, premature ejaculation assessment questionnaire
3
C
Physical examination is necessary for the initial evaluation of premature ejaculation in order to identify underlying disorders associated with premature ejaculation or other sexual dysfunction, particularly with erectile dysfunction.
3
C
Laboratory or neurophysiologic testing should be completed only as indicated, guided by specific findings of the history or physical examination, and is generally not recommended routinely.
3
C
Chapter 5 Treatment of Premature Ejaculation
Adult men are afflicted by premature ejaculation, many of which is due to psychological factors, and therefore their treatment should be limited to sexual life coaching and psychological interventions such as reducing operational anxiety and improving self-confidence [1-3]. Before starting treatment for PE, the patient’s intravaginal ejaculation latency (IELT), duration of PE and its type should be fully assessed, which is particularly important for individualized treatment of premature ejaculation, as well as clarifying whether it is accompanied by ED or other sexual dysfunctions, and the associated diseases such as combined ED, chronic prostatitis, genital tract infection, circumcision and hyperthyroidism need to be treated first or simultaneously [1 , 4-5].
Behavioral therapy is effective in the treatment of PE, but this therapy is time-consuming, requires the cooperation and assistance of sexual partners, is difficult to implement, and its long-term efficacy is unclear. Therefore, in primary PE, behavioral therapy is not recommended as first-line treatment, while it can be considered when patients refuse pharmacological treatment or have difficulty tolerating drug-induced adverse effects [1,3,5]. Pharmacological treatment is the first choice for the treatment of premature ejaculation, and currently selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and topical anaesthetic drugs (TCAs) have varying efficacy in the treatment of primary or secondary PE. In patients with refractory or particularly severe PE (IELT <30-60s or ejaculation before vaginal insertion), oral SSRIs combined with behavioral therapy or topical anaesthetic drugs can achieve better outcomes than monotherapy [1, 3-5].
1. pharmacological treatment
1, 1 Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)
Neuropharmacological studies have found that inhibition of 5-hydroxytryptamine (5-HT) reuptake delays the male ejaculatory impulse. SSRIs exert their function of delaying ejaculation by inhibiting presynaptic membrane 5-HT reuptake, increasing the concentration of 5HT in the synaptic gap, and activating postsynaptic membrane-associated 5-HT receptors to raise the ejaculatory threshold [1,4, 6].
SSRIs and TCAs were originally used for the treatment of depression, but clinical studies found that prolonged use of SSRIs and TCAs delayed ejaculation and thus began to be used for the treatment of premature ejaculation.SSRIs for premature ejaculation take 1-2 weeks to take effect. The SSRIs paroxetine was first reported to be effective in the treatment of premature ejaculation in 1970, and the TCAs clomipramine was reported to be effective in the treatment of PE in 1973. Currently, SSRIs have become the drugs of choice for the treatment of premature ejaculation, and the SSRIs commonly used in clinical practice include dapoxetine, sertraline, paroxetine, fluoxetine, citalopram, fluvoxamine maleate, etc., and the TCAs drugs include clomipramine [1, 3-4].
1, 1, 1 Dapoxetine (Dapoxetine)
Dapoxetine is currently the first and only drug approved by the FDA for the treatment of premature ejaculation. Dapoxetine has been studied in more than 6,000 clinical trials in multiple centers worldwide, its efficacy has been confirmed, and it is now approved for clinical use as a prescription drug for premature ejaculation in several countries [1, 3-4, 6-9]. It is used as an on-demand SSRI for premature ejaculation with a rapid onset of action and short half-life, with rapid absorption reaching its peak at 1 and 5 h.
Dapoxetine has similar efficacy in primary and secondary PE [10]. Adverse effects of dapoxetine are less common [1, 3, 6-10] and mainly include nausea (8, 7%-20, 1%), drowsiness (3, 1%-4, 7%), diarrhea (3, 9%-6, 8%), headache (5, 9%-6, 8%), dizziness (3, 0%-6, 2%), and rhinitis (3, 2%-2, 9%) in a dose-dependent manner. In contrast to other SSRIs, no significant withdrawal syndrome, etc., was observed during treatment with dapoxetine[1, 3-4] .
Evidence from 1a supports the efficacy and safety of on-demand dapoxetine in the treatment of primary and secondary PE.
1, 1, 2 Other non-drug approved labeled SSRIs and TCAs for the treatment of premature ejaculation.
With oral SSRIs and TCAs, delayed ejaculation usually occurs 5-10 days after initiation of treatment, but full onset of effect often requires 2-3 weeks of treatment [3-4]. Because of the time required for receptor desensitization, long-term continuous use is recommended to ensure efficacy. The effect may be maintained for several years, and rapid tolerance usually occurs after 6-12 months. On-demand administration of SSRIs and TCAs 3-6 h before sexual intercourse is less effective than daily administration, although well tolerated by patients [1,4,11]. On-demand dosing can be combined with other treatments or used as a supplement to low-dose daily oral therapy to reduce adverse drug reactions[4] .
There is level 1a evidence supporting the efficacy and safety of daily administration of SSRIs and TCAs for both primary and secondary premature ejaculation.
1, 1, 1, 2, 1 SSRIs
Daily doses of paroxetine 10-40 mg, sertraline 25-200 mg, fluoxetine 10-60 mg, clomipramine 12,5-50 mg, and citalopram 20C40 mg are often effective in delaying ejaculation [1, 3-5]. A Meta-analysis showed that the improvement in IELT from baseline with different types of SSRIs for PE was: paroxetine (20 mg/d): 8-fold, sertraline (50 mg): 5-fold, fluoxetine (20-40 mg): 5-fold, and citalopram (20-40 mg): 2-fold [12]. Limited evidence suggests that citalopram is less effective than other SSRIs for the treatment of premature ejaculation, and fluvoxamine maleate may be ineffective[1] .
Adverse effects of SSRIs for PE are rare, generally mild, and tolerable, often occurring in the first week of treatment and resolving after 2-3 weeks of continuous treatment. Adverse effects include malaise, fatigue, yawning, nausea, dry mouth, diarrhea, or sweating, and others such as decreased libido, loss of sexual pleasure, ED, and non-ejaculation have been reported sporadically [12-18]. Therefore, if patients and their sexual partners have a need for sexual activity and require treatment for PE, they should take the medication for a long time. The occurrence of SSRI withdrawal syndrome should be noted with prolonged or higher doses of SSRIs [19-20].SSRI withdrawal syndrome is the onset of psychosomatic and vegetative symptoms on day 3-4 after abrupt discontinuation or high dose reduction. Therefore, patients who have been taking SSRIs for PE for a long time or at higher doses should be tapered before discontinuation.
1, 1, 1, 2, 2 TCAs
A controlled study of on-demand administration of the TCAs clomipramine 4-6 hours prior to sexual intercourse occurred, and both had differentially prolonged IELT compared to daily administration of the same dose of clomipramine, but the increase in IELT from baseline was lower with on-demand administration than with daily administration [21]. The major adverse effects of clomipramine include fatigue (3C30%), vomiting (30%), dizziness (14%), dry mouth (10C23%), and ED (20%) [22-23]. Based on the inhibition of monoamine oxidase reuptake by clomipramine, clomipramine enhances the effects of endogenous and exogenous catecholamines, manifesting as quinidine-like effects and anti-adrenergic-like effects such as abnormal ECG and the appearance of palpitations.
1.2 Local anesthetic drugs
The use of local anesthetic drugs for the treatment of PE began in 1943 and was one of the first methods used for the pharmacological treatment of PE. They are used for the treatment of premature ejaculation because they can reduce penile sensitivity and prolong the ejaculatory latency without affecting the ejaculatory sensation. Commonly used commercially available local anesthetics to date include lidocaine and/or proparacaine mixes in gel, cream, or spray form, with several small-sample clinical studies demonstrating the effectiveness of lidocaine/proparacaine mixes at approximately 80% (based on patient improvement of self-symptoms or IELT) [24-31]. Large randomized controlled studies evaluating the efficacy of local anesthetic medications for premature ejaculation based on IELT or questionnaire format are still lacking.
The lidocaine/proparacaine mixture should be administered 10-20 min before intercourse, and its adverse effects are dose-related, including numbness of the glans due to overdose, occasional reports of ED, and lack of sexual pleasure in the sexual partner due to vaginal numbness caused by vaginal absorption of the drug during intercourse if the applied drug is not wiped off before sexual intercourse occurs.
There is 1b evidence to support the effectiveness and safety of using local anesthetics for the treatment of primary PE.
1,2,1 Lidocaine-proparacaine cream
The results of a small sample randomized double-blind controlled trial showed that lidocaine-proparacaine cream prolonged IELT from 1 min to 6 or 7 min at baseline in patients with PE.
1,2,2 SS cream
SS cream is a compound preparation made from extracts of various herbs [28-30] and is used by applying it to the head of the penis 1 h before intercourse and washing it off before intercourse.
1, 2, 3 Lidocaine and/or proparacaine spray
A new lidocaine/proparacaine spray, PSD502 [31], is currently in a phase III clinical trial, and preliminary results indicate a 6, 3-fold increase in IELT in the PSD502 treatment group compared to baseline, accompanied by increased ejaculatory control and improved sexual satisfaction.
1. 3 Phosphodiesterase type V (PDE5) inhibitors.
Many studies support the effectiveness of PDE5 inhibitors in the treatment of PE, the exact mechanism of which is unclear. It has been reported in the literature that the ejaculatory latency may be prolonged due to the inhibition of PDE5 activity on the smooth muscles of the ejaculatory ducts, vas deferens, seminal vesicles, and posterior urethra by PDE5 inhibitors, resulting in smooth machine diastole [32-33]. It has also been analyzed in the literature that patients taking PDE5 inhibitors may reduce anxiety and downregulate the sexual arousal threshold of erection due to increased erectile hardness of the patient, thus allowing an increase in the ejaculatory threshold [34-35]. PDE5 inhibitors alone have been reported to increase ejaculatory latency in patients with premature ejaculation, but most scholars advocate the combination, and more literature supports that PDE5 inhibitors combined with SSRIs or local anesthetic drugs are significantly more effective than alone [36-38]. For patients with premature ejaculation in combination with ED, PDE5 inhibitors or combination therapy can be used. For patients with premature ejaculation without ED, this guideline does not recommend PDE5 inhibitors as the treatment of choice.
1, 4 Other drugs
1,4,1 α1-adrenergic receptor antagonists
A small sample of studies has reported the efficacy of α1-adrenergic receptor antagonists in the treatment of PE [39-40]. The possible mechanism is to reduce sympathetic excitability of the ejaculatory ducts such as the vas deferens, prostate and posterior urethral smooth muscle and delay ejaculation. It may also act on alpha receptors in the central nervous system to control the ejaculatory reflex and relieve the symptoms of premature ejaculation by inhibiting the excitability of the central nervous system.
1,4,2 Tramadol
Tramadol is a central opioid receptor agonist that is approved for widespread clinical use as an analgesic. In a placebo-controlled small sample study, tramadol treated 60 patients with primary PE who took tramadol 25 mg as needed 1-2 h before the onset of sexual intercourse, the IELT was prolonged from 1, 17 min to 7, 39 min, while the placebo group increased by 2, 01 min from baseline. nausea, vomiting, dizziness, and drowsiness were the main adverse effects, with incidences of 8%-28%, respectively [41 -42]. Tramadol is only recommended to be considered for specific patients based on the fact that long-term use of tramadol will cause drug addiction and the presence of a high number of adverse effects.
There is 2d evidence of the efficacy and safety of alpha blockers and tramadol for the treatment of premature ejaculation. This guideline is not recommended.
II. Psychological/behavioral treatment
Current psychological treatment for premature ejaculation is often a short-term treatment model that integrates psychodynamic, systemic, behavioral, and cognitive therapies[43] . The goal of psycho-behavioral interventions is to help patients and sexual partners improve ejaculatory control by (i) learning to control and/or delay ejaculation; (ii) increasing confidence in sexual life; (iii) reducing anxiety about sexual life; (iv) changing stereotypical sexual routines; (v) removing barriers related to intimacy; (vi) addressing interpersonal issues that promote and maintain premature ejaculation; (vii) adapting to experiences and thoughts that interfere with sexual life; and (viii) improving communication and exchange with (8) improve communication and exchange with sexual partners [44]. Psychotherapy is indicated for patients in whom psychosocial factors are clearly contributing and maintaining factors of premature ejaculation and medication alone is not effective. Combined with pharmacological treatment, it helps to improve the efficacy of pharmacological treatment, patients learn to control ejaculation after stopping medication, enhance patients’ sexual confidence, and improve the sexual satisfaction of both partners. Therefore, it has been suggested that combined pharmacological and psychological treatment should be the first-line treatment option for premature ejaculation [45,46]. A number of studies have confirmed that psychotherapy can achieve short-term efficacy, but studies on long-term efficacy are relatively limited [47]. Psychotherapy may be more effective than primary PE and secondary PE for situational PE or premature ejaculatory-like ejaculatory dysfunction.
Psychological treatment is also influenced by several factors, such as the cost of treatment, the skill level of the therapist, and the desire of the patient and sexual partner to seek treatment. Patients who are energetic, hopeful, and have a regular and cooperative sexual partner often have better outcomes [48].
1, General psychotherapy: including psychological education, creating a warm sexual environment to relieve anxiety as an important maintenance factor of premature ejaculation, and reducing the intensity of sympathetic nerve activity, thus lowering the ejaculatory threshold [49].
2. Behavioral therapy
Behavioral therapies began in the 1950s and include Semans’ pause training [50], Masters and Johnson’s “pause and squeeze” technique [51], and Kaplan’s “stop-and-go” technique [43]. These are the standard treatment techniques for PE. Patients go through a series of progressive training sessions to build ejaculatory control. The approach starts with self-stimulation, switching to partner stimulation, followed by non-pumping intercourse, and finally the “stop-motion-stop” technique. This repeated training weakens the patient’s response to sexual stimulation so that the patient can receive more stimulation, maintain the appropriate intensity of stimulation at the ejaculatory threshold and prolong the duration of stimulation. Studies have reported that behavioral therapy can prolong IELT and improve patients’ sexual confidence and self-esteem.
The purpose of the “stop-and-go” technique is to increase the ejaculatory stimulation threshold. The partner stimulates the patient’s penis until the patient feels ejaculation is imminent, then immediately stops stimulation, waits until the ejaculation anticipation has completely disappeared, then re-stimulates, and then completes ejaculation three times. This raises the ejaculatory stimulation threshold, thereby relieving the urgency of ejaculation, strengthening the ability to inhibit ejaculation, and prolonging the ejaculatory latency. Training should be done 3 times a week until the patient is able to control ejaculation better.
The specific method of the “squeeze and pinch” technique is for the woman to place her thumb at the tether of the penis and her index finger and middle finger below the coronal sulcus, squeeze and press the head of the penis for 3 to 4 seconds, and when the ejaculation threshold is reached, the spouse holds the body of the penis with force until the ejaculation sensation disappears.
Recently, some people use sexual function therapy devices to desensitize patients with premature ejaculation, through physical stimulation in order to train the patient’s ability to control ejaculation, so that the patient can master the intensity of stimulation to reach his or her ejaculatory threshold to delay ejaculation, the principle of which is similar to behavioral therapy and is effective in about half of patients. The guidelines recommend considering a combination for patients for whom pharmacological treatment is ineffective and less effective.
Masturbation before sexual intercourse is a frequent method used by many young patients with PE. Masturbation decreases penile sensitivity after ejaculation and prolongs the ejaculatory latency during the inactivity period.
Behavioral therapy for PE, although in the short term to achieve a certain degree of effectiveness, but because of the need for long-term close cooperation with the female partner, many patients because of the difficulty of persistence and affect the long-term results. Behavioral therapy is generally effective in about 2 weeks and can be continued for 3-6 months to consolidate the effect.
3.Cognitive therapy
Cognitive therapy focuses on targeted perception and experience, improving sexual communication between sexual partners, improving sexual skills and self-confidence, and reducing anxiety related to sexual activity [52].
Psychodynamic and muscle relaxation therapies are also available.
The evidence regarding the effectiveness of psycho-behavioral interventions for PE is at the 2b level.
III. Surgical treatment
For patients with primary PE who have difficulty with behavioral and/or pharmacological treatments, surgical treatment has been reported in the literature, including selective dorsal penile neurectomy and glans penis enlargement with hyaluronic acid gel. Several single-center small sample clinical studies have reported selective dorsal penile neurectomy for primary PE with some recent efficacy [53,54], but its overall and long-term efficacy has yet to be However, its overall and long-term efficacy has yet to be further explored and studied in a multicenter, large sample with long-term follow-up.
Based on the fact that the currently reported clinical studies on surgical treatment of premature ejaculation are single-center, small-sample, non-randomized controlled studies, there is a lack of evidence-based medical evidence and long-term follow-up data in large samples, and the risks of surgical procedures may lead to hyposensitivity, ED, or even permanent loss of penile erectile function, which far outweigh the benefits. Therefore, this guideline recommends caution in its adoption and does not routinely recommend it.
PE surgical treatment is a Level 4 level of evidence.
Treatment Guidelines
Recommendation Evidence-based level Level of recommendation
1, Combined ED or other sexual dysfunction and genitourinary tract infection need to be treated first 2a B
2, Behavioral treatment of PE is effective, but requires longer time and spousal cooperation and is more difficult to implement 3 C
3. Drugs are the first choice for the treatment of primary PE 1a A
4, SSRIs are the first-line drugs for PE treatment 1a A
5, Local anesthetics as an alternative treatment to SSRIs 1b A
6. PE may recur after treatment cessation 1b A
7. Behavioral therapy can enhance the effect of drug treatment and prevent relapse 3 C
Attachment: Treatment process of PE
1. Based on patient and sexual partner
IELT, degree of self-control of ejaculation, degree of annoyance/depression, time of PE initiation and duration, type of PE, patient’s psychological status, relationship problems with sexual partners, medication history, etc.
2. Treatment of PE
Patient’s expectations, discussion with patient/sexual partner about treatment (medication, psychological/behavioral therapy or combination therapy), if PE is secondary to ED or chronic prostatitis, treatment of PE is preferred or concurrent treatment of co-morbidities.
3. Gradual withdrawal of medication after 6-8 weeks.