Non-pharmacological approaches for treatment of premature ejaculation: a systematic review

Abstract

Premature ejaculation is a common male condition worldwide with prevalence estimates varying from 30% to 85%. Owing to the lack of a clear definition and a clear understanding of the potentially multifactorial pathophysiology, treatment remains challenging. The aim of this systematic review was to evaluate the non-pharmacological treatment modalities for PE to inform clinical practice and patients.

Despite the high number of scientific studies in the literature, conclusive data are still lacking. Indeed, although a number of management options for premature ejaculation (PE) exist, to date, there is no general consensus on the gold standard for people suffering with this condition. Most probably the combination of pharmacological, behavioural and psychological approaches is the most beneficial for PE.

PE is broadly defined as when semen leaves the body (ejaculate) sooner than wanted during sex.¹ The exact prevalence of PE in various populations groups is debated. Rosen has described PE as the most common sexual dysfunction in men and found that it was reported by approximately 30% of the population.² Gao and Zhang found that 30–50% of the male population are affected by this condition,³ whereas Shaeer and Shaeer found a much higher prevalence of approximately 83%.⁴ The large variations are likely owing to a lack of a widely accepted, standardised definition of PE, which makes study design and conduction of clinical trials more difficult. Moreover, differences in reporting PE are likely influenced by cultural context and patient expectation.

The first definition of PE was introduced by Masters and Johnson in 1970 as ‘the inability of a man to delay ejaculation long enough for his partner to reach orgasm on 50% of intercourse attempts’.⁵ The International Society of Sexual Medicine defined PE in 2014 as ejaculation that always or nearly always occurs prior to or within about one minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about three minutes or less (acquired PE).⁶ PE is often considered as a stand-alone condition; however, up to 50% of PE patients also suffer from erectile dysfunction. Thus, Colonnello et al. proposed a unifying definition for PE that is associated with erectile dysfunction in one entity: ‘loss of control of erection and ejaculation (LCEE)’.⁷ This change of paradigm has clinical implications for patients in relation to PE and ED screening as well as treatment of this condition.

Because of the lack of a clear definition and a clear understanding of the potentially multifactorial pathophysiology, the treatment for PE has remained challenging. This is of significant concern as PE is associated with detrimental health outcomes, including, for example, psychological distress, poor self-esteem, anxiety, erectile dysfunction, decreased libido and poor interpersonal relationships.⁸ Importantly, few pharmacological treatments for PE are available and have unwanted side-effects. For example, serotonin inhibits ejaculation and its effects are potentiated by tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). TCAs are effective, but infrequently used because they have prominent side-effects, including nausea, dry mouth, erectile dysfunction, hot flushes and cardiotoxicity.⁸ Whereas, anaesthetic aerosols and creams containing lignocaine, lignocaine/prilocaine or herbal-derived anaesthetic agents are applied to the glans penis well ahead of sexual intercourse and should be used in conjunction with condoms to avoid numbness in the partner's genitals.⁸ Thus, non-pharmacological approaches may be preferred to treat PE due to the reduced number of side-effects. However, to date, no attempt has been made to collate and evaluate the literature on non-pharmacological interventions for PE. Such a review is of upmost importance in order to guide clinical practice and patients alike.

Given this background, the aim of this systematic review was to collate and evaluate the non-pharmacological treatment modalities (eg behavioural, alternative medicine and surgical) for PE to inform clinical practice and patients.

Methods

This systematic review adhered to the PRISMA⁹ and MOOSE¹⁰ statements and followed a structured protocol available under reasonable request from the corresponding author.

Search strategy

Two investigators (MT and DP) independently conducted a literature search using Medline/PubMed, Scopus, ERIC, CINAHL, PsycINFO and Embase databases from inception to 27 June 2022. The following search strategy was used: ‘premature ejaculation’ OR ‘early ejaculation’ OR ‘rapid ejaculation’ OR ‘rapid climax’ OR ‘premature climax’ OR ‘ejaculation praecox’ OR ‘praecox ejaculation’) AND (‘treatment’ OR ‘management’ OR ‘approach’ OR ‘behaviour’). The references of retrieved articles together with the proceedings of relevant conferences were hand-searched to identify other potentially eligible studies for inclusion in the analysis missed by the initial search or any unpublished data. The search results were independently screened by at least two investigators (DO, RL, MAT, JJW). The results were then compared, and in case of discrepancies, a consensus was reached with the involvement of a third senior investigator (LS). There was no language restriction applied.

Type of studies, inclusion and exclusion criteria

Following the PICOS (participants, intervention, controls, outcomes, study design) criteria, we included studies assessing:

P: Male suffering PE, defined using any definition

I: Non-pharmacological interventions

C: Males undergoing pharmacological or no treatment

O: Effects of non-pharmacological interventions on PE

S: Observational (retrospective, cross-sectional, prospective) and experimental studies.

Studies were excluded if they had no data on non-pharmacological treatments.

Data extraction and statistical analyses

For each eligible study, two independent investigators (DP, MAT, RL, JJW) extracted: name of the first author and year of publication, article type, study design, sample size, sample characteristics, PE definition, intervention, outcome measures and findings.

Outcomes

The primary outcome was the effect of non-pharmacological interventions on PE.

Assessment of study quality

Two independent authors (DP, MT) assessed the quality of studies using the Newcastle-Ottawa Scale (NOS).¹¹ The NOS assigns a maximum of 9 points based on three quality parameters: selection, comparability and outcome. As per the NOS grading in past reviews, we graded studies as having a high (<5 stars), moderate (5–7 stars) or low risk of bias (≥8 stars).¹²

Assessment of the certainty of evidence

To ascertain the certainty of the evidence, the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used.¹³

Results

As shown in Figure 1, we initially found 1827 potentially eligible articles. After removing 1736 papers through the title/abstract screening, 91 were retrieved as full text. Of the 91 full text, 36 studies were excluded because they were theoretical, opinion, focused on erectile dysfunction or included only pharmacological treatments, leaving 54 studies to be included in the systematic review.^14-67

Figure 1

PRISMA flowchart

The 54 studies included a total of 3485 participants. The majority of the studies (n=19) were conducted in Europe, 13 in Asia, 12 in the Middle East, 6 in North America, 2 in Africa, 1 in Oceania and 1 in South America. The descriptive characteristics of the included studies and their main findings are reported in Appendix 1.

No publication bias test was performed. The median quality of the studies was 6.2 (range 4–9), indicating an overall more than satisfactory quality of the included studies. Because of high heterogeneity, the certainty of this evidence according to the GRADE framework has been rated as moderate.

Narrative summary and discussion

The treatment of PE has remained heterogenous owing to the lack of a uniform definition and understanding of the cause of this condition. Before deciding on the best approach to PE treatment, it is important to understand patients’ needs and expectations. PE is associated with a higher risk of erectile dysfunction, so erectile dysfunction should be diagnosed and treated before treating PE.⁷ It is also important to treat prostatitis as it is a reversable cause of PE.⁶⁸

The only approved pharmacological treatment (but not in the USA) for PE is dapoxetine. Off-label pharmacological options include local anaesthetics and clomipramine, SSRIs and tramadol. Encouragingly, European Association of Urology guidelines recommend behavioural therapy in combination with pharmacological treatment.⁶⁹ Our systematic review has collated and evaluated the non-pharmacological treatment options for PE in the academic literature.

The last century was marked by the landmark book by Masters and Johnson, Human Sexual Inadequacy, and the approach to managing sexual dysfunction by regarding the couple relationship itself as the patient.⁵

The earliest academic paper identified in our systematic review was published in 1974. It explored the effectiveness of group treatment for PE in a prospective pilot study of four heterosexual couples with a mean age of 37.8 years. Two were successfully treated in six 45-minute group sessions, and two gained successful ejaculatory continence two months later. At four months follow-up, all four couples reported continued and improved sexual functioning. Therapist time average was 1.5 hours per couple.³⁴

Psychotherapy in various forms (sex therapy, couple therapy, brief therapy) were the main approaches reported on for managing PE in the last century. A notable exception to this approach is the paper by La Pera and Nicastro³⁸ in which they presented the evaluation of pelvic floor rehabilitation as a treatment for PE. Eighteen patients with premature ejaculation were recruited. Fifteen (83%) of them had suffered from this disturbance for at least five years. Most of them had experienced other therapies without success. After 15–20 sessions of pelvic floor rehabilitation, 11 (61%) patients were cured and were able to control the ejaculatory reflex; 7 (39%) patients had no improvement. All patients were followed for a minimum of 6 months to a maximum of 14 months. Subsequent studies have also described the potential benefit of this approach.³⁹

The first report of using technology for treatment of PE was published by Optale et al. in 1998, who examined the effect of integrating 12 one-hour full-immersion virtual reality sessions with psychotherapy in 16 patients.⁴⁶ The authors reported lasting improvement at the last follow-up at six months post-therapy. The same group of authors carried out a further two studies looking at the same approach and reported improvements at 12 months.^{47, 48}

Another use of technology to manage PE was explored by Optale.⁴⁹ In this study, all patients entered a cycle of 15 sessions of psychodynamic psychotherapy integrating behavioral therapy, each lasting about 45 minutes. Thirty-two patients were randomly assigned to two groups, each of which performed daily homework exercises (physiotherapy exercises for reinforcing the pelvic floor muscles and cognitive exercises for distancing from sexual failure). The first group (15 patients) received verbal and printed instructions only (treatment as usual), whereas the second group (17 patients) experienced the exercises with guidance from a mobile app. In both groups the exercises started after the seventh session. Patients were advised to perform the exercises three times a day for three months. Analysis of the data revealed significant pre-post improvements in Premature Ejaculation Diagnostic Tool (PEDT) and Premature Ejaculation Profile (PEP) scores for the app group compared with those of the ‘treatment as usual’ group (p<0.01). The frequency of patients with no-PE condition for the app group after treatment was significantly higher than the frequency of patients with no-PE condition for the ‘treatment as usual’ group (p<0.001).⁴⁹

In a sample of 31 patients, Abdel-Hamid et al. compared efficacy and safety of clomipramine, sertraline, paroxetine, sildenafil and the pause-squeeze technique in the treatment of PE in a double-blind crossover study.¹⁴ All treatment modalities showed statistically significant increases in the intravaginal ejaculation latency time (IELT) (p=0.0001). The pause-squeeze technique increased latency time from a median of 1 minute to 3 minutes. Interestingly, sildenafil was the most effective treatment, increasing latency time from 1 minute to 15 minutes; this can be explained by the association between the two pathologies, PE and erectile dysfunction.

Other modalities have been found to be potentially effective in small clinical trials such as desensitisation of the dorsal nerves with pulsed radiofrequency modulation¹⁸ or acupuncture.⁶³ A randomised controlled trial assessing changes in IELT and PEDT scores reported that the most efficient treatment was dapoxetine (60mg) when compared with dapoxetine (30mg) or acupuncture. Moreover, dapoxentine (30mg) was superior to acupuncture and acupuncture yielded improved results when compared with sham acupuncture (p<0.001).⁶¹

Kempeneers et al. investigated the role of bibliotherapy in the management of PE and published two papers on this topic, including a randomised controlled trial with 71 patients and found that there was no statistically significant difference in the self-help group (booklet) compared with the group that received the booklet and support from a therapist.^{35, 36}

Mantovani compared the efficacy of dapoxetine (30mg; group 1, n=6) with dynamic rehabilitative treatment consisting of toning the pubococcygeus (group 2, n=6) and a combination of both (group 3, n=6).⁴¹ In group 1, 75% of patients were cured (PEDT score) at six months and 25% at six months. In group 2, 25% of patients were cured at three months and 25% at six months. In group 3, 75% of patients were cured at three months and 50% at six months.⁴³

A study involving a sample of 105 patients with diagnosed PE examined the value of physical activity (moderate running for at least 30 minutes for five days a week for 30 days) compared with dapoxetine (30mg) for 30 days in PE patients. Both groups reached a statistically significant improvement in IELT compared with the control group (advised to walk no more than 30 minutes a day for five days in a week). Interestingly, between the dapoxetine and the physical activity group there was no significant difference (p=0.73). In another study, Makwana and Patil (2012) found an improvement in IELT in a randomised trial with statistically significant differences between pre- and post-yoga activity.⁴⁰ Similar findings were also described by Mamidi and Gupta, a year later, this time using a Premature Ejaculation Severity Index (PESI).⁴²

Desensitising the penis glans is a proposed mechanism to help in the management of PE. In one study including nine participants, masturbation was performed using the Tenga Flip masturbation aid five times per week for six weeks; IELT increased up to 57% during masturbation and up to 79.9% during coitus.⁵⁴ Other approaches to desensitise the glans have utilised surgery. In one study including a cohort of 224 patients, penile surgery with allogenic dermal graft led to prolonged time between preoperative and postoperative ejaculatory time of 7 minutes on average (from 1 minute to 17 minutes).³⁰ Another surgical technique includes cutting the bulbospongiosus muscle bilaterally and frenular delta excision.¹⁶ The operation performed on 60 patients in a longitudinal study had a 96.6% success rate, IELT time increased 200–1000%.¹⁶ A surgical variation that can also improve IELT was proposed by Zhang who found in 39 patients that compared with baseline data, IELT scores increased, and PE was relieved at six months and two years after operation.⁶⁷ They used an inner condom made of acellular dermal matrix, which was transferred to the subcutaneous pocket of the penis for penis augmentation. The same surgical technique was reported by Wang et al. who found that the surgical intervention significantly increased the average IELT in 20 patients, from 0.67 to 2.37 minutes (p=0.009).⁶⁶ Moreover, one study including five patients investigated the efficacy of a computed tomography-guided pudendal nerve block at the level of the sacrospinous ligament and the Alcock's canal in patients with refractory PE.¹⁷ The overall IELT differed significantly before and after treatment (21.94 versus 215.42 seconds; p=0.039). IIEF-5, PEDT and Sexual Quality of Life – Male Version scale also differed significantly before and after treatment. No complications for the CT-guided infiltration were recorded.¹⁷

One study evaluated the efficacy and safety of transcutaneous posterior tibial nerve stimulation (TPTNS; consisting of 30-minute sessions of the application of 20Hz with a pulse amplitude of 200μsec). The intensity was adjusted based on individual sensitivity. Participants received three weekly sessions for 12 consecutive weeks. Follow-up continued for nine months after therapy completion. Eleven patients completed therapy, and 54.5% (p=0.037) showed tripled baseline IELT scores at week 12. The IELT increased 4.8-fold, 6.8-fold and 5.4-fold at weeks 12, 24 and 48, respectively.⁶⁴ TPTNS was also explored by Shechter and colleagues in a prospective single-blinded self-controlled study including 23 patients. They reported that during the active transfunctional electrical stimulation treatment, mean masturbation ejaculatory latency time was significantly longer than the sham treatment (311.4±237.14 seconds versus 124.6±107.02 seconds, p=0.0009). This difference represents an averaged time-fold increase of 3.49±3.12 minutes in masturbation ejaculation latency time.⁶²

Conclusion

An important limitation of the present review is that the majority of studies included small samples with fewer than 50 patients.

In conclusion, PE has been managed with various non-pharmacological approaches (eg behavioural and surgical approaches) that have been found to be effective in relatively small randomised controlled trials. Specifically, the potential of physical activity promotion for the management of PE should be investigated further. Moreover, larger randomised controlled trials are urgently needed to further guide clinicians to select the best option for different groups of patients.

Declaration of interests

All authors declare no conflict of interest. Dr Guillermo F López Sánchez is funded by the European Union – Next Generation EU.

Key points

• Premature ejaculation (PE) is common, affecting 30–85% 0f men worldwide
• No clear definition or understating of PE means treatment is challenging
• There are few pharmacological treatments for PE: most are off-label and associated with side-effects such as nausea, dry mouth, erectile dysfunction, hot flushes and cardiotoxicity, so non-pharmacological management may be preferred
• A number of non-pharmacological treatments for PE have shown efficacy and some, such as physical activity, warrant further investigation

Appendix 1: Summary of descriptive characteristics and main findings of included studies

Author and date	Aim	Article type	Study design	Sample size (if applicable)	Sample characteristics (age, other comorbidities, other sexual dysfunctions, hormone profile)	Premature ejaculation definition	Intervention	Outcome measures	Findings
Abdel-Hamid, 2001^14	To compare the efficacy and safety of the as-needed use of clomipramine, sertraline, paroxetine, sildenafil and the pause-squeeze technique in treatment of primary premature ejaculation (PE)	Journal article	Double-blind randomised crossover study	31	Mean age of intervention group (SD): 34.09 (4.29) years Mean age of control group (SD): 34.8 (6.44) years Participants with history of a psychiatric disorder or current physical illness were excluded	Intravaginal ejaculation latency time (IELT) <2 minutes and patient complained of little, if any, control over their ejaculation	4-week consecutive treatment periods, each separated by a two-week washout. Patients were randomly assigned to receive each of the 4 drugs and use pause-squeeze on as-needed basis Drugs administered 3–5 hours before anticipated intercourse	Anxiety scores, ejaculation latency time, sexual satisfaction score	Clomipramine, sertraline, paroxetine, sildenafil and pause-squeeze technique as needed resulted in a statistically significant and clinically relevant delay of IELT (all p=0.0001). Sildenafil was the most effective treatment
Akasheh, 2014^15	To investigate the effects of sertraline on semen parameters and compare its effect with behavioural therapy in men with primary PE	Journal article	Single-blind clinical trial	60	Mean age sertraline group (SD): 24.63 (3.02) years Mean age control group (SD): 24.93 (3.15) years Men with other sexual disorders or chronic psychiatric or physical illness excluded	At all or nearly all intercourse attempts with all or nearly all women in most cases within 1 minute and consistent during the life	2 groups: sertraline group (n=30, sertraline 25mg/day for 1 week followed by 50mg/day for 3 months) and behavioural therapy group (n=30, using behavioural therapy technique [included start-stop technique and squeeze technique] for 3 months)	Semen analysis	No significant change in semen parameters in patients treated using behavioural therapy; however, following sertraline treatment sperm concentration and percentage of normal morphology significantly reduced
Aglan, 2018^16	To present effectiveness of cutting the bulbospongiosus muscle bilaterally and frenular delta excision for treatment of PE	Abstract	Longitudinal	60	Not specified	Not specified	Operative surgery	IELT	The operation had a 96.6% success rate, IELT time increased 200–1000%,
Aoun, 2020^17	To investigate efficacy and safety of a computed tomography-guided pudendal nerve block at the level of sacrospinous ligament and Alcock's canal in patients with PE refractory to conventional pharmacological treatment	Journal article	Prospective pilot study	5	Mean age (SD): 27 (6) years All participants had a score >16 in the 5-item version of the International Index of Erectile Function (IIEF-5) Patients with thyroid problem, diabetes mellitus, neurological disease excluded	>11 in the Premature Ejaculation Diagnostic Tool (PEDT)	Computed tomography-guided pudendal nerve block	IELT, IIEF-5, PEDT, Sexual Quality of Life–Male version (SQoL-M).	Overall IELT differed significantly before and after treatment (21.94 vs 215.42 seconds; p=0.039). IIEF-5, PEDT and SQoL-M also differed significantly before and after treatment. No complications for CT-guided infiltration recorded
Basal, 2010^18	To evaluate efficacy of pulsed radiofrequency (PRF) neuromodulation in the treatment of PE	Journal article	Longitudinal	15	Mean age (SD): 39 (9) years Patients with erectile dysfunction excluded	IELT <1 minute	PRF neuromodulation to desensitise dorsal penile nerves	IELT, sexual satisfaction scores	IELT increased from a mean of 18.5 (SD, 17.9) seconds to 139.9 (55.1) seconds at follow-up. Significant increase in partners’ and patients’ sexual satisfaction scores after treatment
Bush, 2014^19	To describe use of a non-prescribed aid (black stone) for PE that resulted in a chemical burn on penis with appearance similar to severe balanitis	Journal article	Case report	1	Age: 37 years No history of sexually transmitted infection, HIV or medical history	Not specified	A black stone with no packaging or official instructions, reputedly from Jamaica. The man was instructed to rub the stone with the tip of a wetted finger and then rub the head of his penis with his finger. Repeated 5–6 times	Observations in a walk-in clinic, glucose testing, full screen for sexually transmitted infections and culture of discharge taken	Application of stone resulted in swollen erythematous glans, chemical burn and sub-preputial discharge Use of unregulated treatments likely to grow and side-effects under-reported
Choi, 2012^20	To evaluate efficacy and safety of extract of ginseng berry on sexual function in men with erectile dysfunction	Journal article	RCT	119 (intervention group = 59, control group = 59)	Intervention group: Mean age (SD): 57.49 (7.94) years Cardiovascular disorders: 34% Gastrointestinal disorders: 4% Genitourinary disorders: 28% Testosterone (ng/mL): 500.53 (189.58) Prolactin (ng/mL): 7.12 (4.26) Control group: Mean age (SD): 57.32 (8.41 Cardiovascular disorders: 23% Gastrointestinal disorders: 3% Genitourinary disorders: 21.05% Testosterone (ng/mL): 482.05 (171.83) Prolactin (ng/mL): 6.39 (4.84)	IIEF-5 scores 13–21	4 tablets of either standardised Korean ginseng berry (SKGB, 350mg ginseng berry extract per tablet) or placebo, daily, for 8 weeks	IIEF-15, PEDT, total cholesterol, high- density lipoprotein, low-density lipoprotein, testosterone, prolactin	PEDT score improved in SKBG group from 9.14 to 7.97 and 7.53 at 4 and 8 weeks, respectively. Both inter- and within-group analysis revealed statistically significant differences (p=0.05)
Dasdemir Ilkhan, 2020^21	To evaluate association of PE with obstructive sleep apnoea syndrome (OSAS), which is characterised by chronic oxidative stress, and to assess effects of continuous positive airway pressure (CPAP) therapy on PE	Journal article	RCT	247 (control subjects without OSAS = 80; patients with moderate OSAS = 85; patients with severe OSAS = 82)	Control: Mean age: 39.17 (6.68) years TSH (μIU/mL): 1.29 (0.39) FT4 (ng/dL): 1.13 (0.14) FT3 (ng/dL) 3.68 (0.31) Total testosterone (pmol/L): 325.00 (53.58) Hypertension: 22.5% Diabetes mellitus: 11.2% Coronary artery disease: 6.2% Moderate OSAS: Mean age: 39.44 (6.51) TSH (μIU/mL): 1.27 (0.36) FT4 (ng/dL): 1.09 (0.10) FT3 (ng/dL): 3.65 (0.25) Total testosterone (pmol/L): 311.18 (46.62) Hypertension: 24.7% Diabetes mellitus: 11.7% Coronary artery disease: 5.8% Severe OSAS: Mean age: 40.20 (5.44) years TSH (μIU/mL): 1.37 (0.41) FT4 (ng/dL): 1.07 (0.09) FT3 (ng/dL): 3.71 (0.39) Total testosterone (pmol/L): 297.03 (41.86) Hypertension: 21.9% Diabetes mellitus: 13.7% Coronary artery disease: 8.5%	International Society for Sexual Medicine (ISSM) definition: the inability to delay or control ejaculation, which consistently occurs before or within 1 minute of penetration, which is accompanied by negative personal consequences, such as distress, bother, frustration and/or avoidance of sexual intimacy	1 year of CPAP therapy	Arabic Index of Premature Ejaculation, IELT, OSAS	Arabic Index of Premature Ejaculation and IELT scores improved significantly in both OSAS groups after 1 year of CPAP therapy
De Amicis, 1985^22	To conduct an outcome and follow-up evaluation of sex therapy	Journal article	Longitudinal	Total sample: 38 couples (20 men had PE)	Men in the sample (including those without PE), mean age (SD) 37.6 (13.11) years	Multiaxial problem-oriented system for classifying sexual dysfunctions	Couples received sex therapy once a week for 15–20 weeks dependent on participants’ needs	Sexual Interaction Inventory, the Locke-Wallace Marriage Inventory and the Sexual History Form	Duration of intercourse for PE men also showed a dramatic increase at the end of therapy, but followed by a gradual regression to pretherapy levels at 3 years (F (3, 63) = 17.01, p<0.001)
De Carufel, 2006^23	To compare efficacy of a functional-sexological treatment for premature ejaculation with behavioural treatment composed essentially of squeeze and stop and start techniques	Journal article	RCT	Total sample: 36 couples	Behavioural group, mean age (SD): 33.4 (5.9) years Functional-sexological treatment group, mean age (SD): 35.6 (4.9) years No significant different between treatment groups and control groups	Ejaculation less than 2 minutes into intercourse	Modulation of sexual excitement through focusing on the temporal, spatial and energetic dimensions of movements	Duration of intercourse, perceived duration of intercourse, Hudson's Index of Sexual Satisfaction, Sexual Interaction Inventory	Significant increase in duration of intercourse between pre- and post-treatment (F = 51.70, p<0.05) and between pre-treatment and follow-up (F = 46.56, p<0.05). No significant changes observed in control group
Genov, 2019^24	To report case of microsurgical denervation of penis in men with lifelong PE after conservative treatment failed	Journal article	Case report	1	Age: 23 years	Not specified	Microsurgical denervation of penis	Penile sensitivity, PEDT, PEP, IIEF-5	Mean PEDT score 19 preoperatively and decreased to 9 at 6th month timepoint and to 7, 12 months after surgery
Gentry, 1978^25	To report on the successful resolution of PE in a patient through brief therapy	Journal article	Case report	1	Age: 37 years	Not specified	8 weeks of 1 hour brief therapy session per week	Self-reported termination of PE	On session 8 patient reported no PE, and at 12-month follow-up reported no return of symptomatic behaviour
Golden, 1978^26	To compare effects of group couples therapy with couple therapy alone on PE among men and female partners with secondary orgasmic dysfunction	Journal article	Between-groups design	15 couples (5 treated alone, 10 treated in groups)	Mean age of men: 28 years	The male self-reported dissatisfaction with lack of control over timing of ejaculation	12 weekly therapy sessions including sex education, attitude restructuring, and specific suggestions for acquiring ejaculator/control for the men and an increased range of orgasmic response for the females. Homework assignments included	Sexual Interaction Inventory, Marital Adjustment Questionnaire, latency from intromission to ejaculation	Significant improvement in latency time in both groups regardless of treatment (p<0.05)
Gupta, 1989^27	To test modified Masters and Johnson technique in treatment of sexual inadequacy	Journal article	Quasi-experimental	21 men (13 on modified Masters and Johnson technique and antidepressants; 8 modified Masters and Johnson technique only)	Married men aged 25–44 years from middle-class families engaged in white collar jobs Either had erectile dysfunction, PE or both 13 developed depression after diagnosis	PE was condition in which ejaculation occurred involuntarily before intromission	A minimum of 15 and a maximum of 25 weekly sessions (one hour each) using modified Masters and Johnson technique. The number of sessions was tailor-made for each case based on quality and quantity of response	Successful cases, defined as satisfactory coitus during treatment and continued performance for at least two months during follow-up	Overall success rate: 76.2% Best results in 30–39 year age group (80%) Recovery rate in primary cases was 75.3%; 83.3% in secondary group Best results obtained in cases who suffered for between 1 and 3 years (90.9%)
Hosseini, 2007^28	To determine whether a constriction ring (part of vacuum device) can increase the IELT	Journal article (brief report)	Longitudinal	42	Mean (range) age 24 (20–33) years. Exclusion criteria: use of drugs with side-effects on ejaculation, penile anomalies and surgery, lower urinary tract symptoms (including prostatitis), psychological diseases and erectile dysfunction	Lifelong PE; men with IELT of <1 minute	After obtaining a full erection, constriction ring (ErecAid; Osbon Medical System, Augusta, GA, USA) placed around base of penis. Took place over a 4-week period	IELT measured using a stop watch	Median IELT 42 (33–54) seconds before treatment and 46 (31–55) seconds after 4 weeks using ring, with no statistically significant difference in IELT before and after treatment (p=0.1) No major complications
Hosseini, 2019^29	To determine impact of varicocelectomy on urine dopamine value in patients with both PE and varicocele	Journal article	Prospective clinical trial	60	Age: 27.5±3.9 years Grade of varicocele (Grade 2 = 23; Grade 3 = 32) Duration of PE diagnosis: 6.9±1.8 years Referral due to infertility Exclusion criteria: previous or current history of antipsychotic use and utilisation of other drugs affecting dopamine level, as well as persistent varicocele after surgery as observed in clinical examination and confirmed by Doppler ultrasound study of pampiniform plexus	IELT values, measured via a stopwatch by partner; those with average last 3 IELT values <60 seconds diagnosed with PE	All the patients underwent inguinal or subinguinal, microscopic-assisted varicocelectomy	24-hour urine dopamine level; 24-hour urine creatinine and volume; IELT measured using a stop watch	Mean 24-hour urine volumes before and after operation were 814.8±169.9 and 808.7±144.7mL respectively (p>0.05). Mean initial and final 24-hour urine creatinine levels were 1325.7±335.2 and 1410.7±398.2mg respectively (p>0.05). Mean initial and final 24-hour urine dopamine levels statistically significant different (p=0.0001). Grade of varicocele not related to dopamine level (p>0.05) Three months after surgery, mean IELT values non-significantly different at 55±14 seconds (p>0.05) Increase in urine dopamine level assessed 1 month after varicocelectomy improved IELT but not significantly (p>0.05)
Jang, 2017^30	To evaluate a newly developed surgical treatment to treat PE patients	Conference abstract	Longitudinal	224	Not specified	Not specified	Penile surgery with allogenic dermal graft	Ejaculatory time	Prolonged time between preoperative and postoperative ejaculatory time was 7 minutes on average (1 to 17 minutes)
Jannini, 2011^31	The following real-life scenarios from different countries show various aspects and mosaics of PE, regarding its manifestation and existence with other concomitant sexual or urological complaints	Journal article	Multiple case reports	7	CR1: 26 years old, unemployed CR2: 29 years old CR3: Age not reported CR4: Early 40s CR5: 20 years old	Not specified	CR1: Progressive stop-start exercises individually then with partner CR2: Counselling and pharmacotherapy CR3: Change position CR4: Psychosexual counselling and pharmacotherapy CR5: Psychosexual counselling and pharmacotherapy	IELT; self-reported sexual satisfaction	CR1: IELT increased to >4 minutes CR2: IELT increased to 3 minutes CR3: IELT with new partner now matched previous IELT CR4: Improved ejaculatory control CR5: Increased IELT
Jern, 2014^32	The present study aimed to replicate a recent study showing promising results for a behavioural treatment intervention using a handheld, vibrating stimulation device in a variation of the classical stop-start technique first introduced by Semans in 1956	Journal article	Randomised, waitlist-controlled pilot study	13	Mean age 49.3±10.2 years Not currently using antidepressant Stopped using SSRI (paroxetine, dapoxetine or both) to treat PE for ≥6 months	ISSM diagnostic criteria: ejaculatory latencies during vaginal intercourse of ‘about one minute’ or less; inability to delay ejaculation on ‘all or nearly all’ vaginal penetrations; and negative personal consequences	Intervention consisted of completing a training programme with masturbation exercises 3 times per week for 6 weeks using a small, stimulating device equipped with a battery-powered vibrator	IELT measured by stop watch; Checklist for Early Ejaculation Symptoms (CHEES) score	Treatment group significantly improved IELT at post-treatment versus pre-treatment (p=0.019) but not CHEES score (p=0.419) IELT and CHEES score significantly improved from pre-treatment to 6 months follow-up (p=0.008 and p=0.006 respectively)
Jiang, 2020^33	To explore efficacy of regular penis-root masturbation (PRM) versus Kegel exercise (KE) in treatment of primary PE	Journal article	Quasi-RCT	37	PRM group: age 31.4±8.4 years; course of disease 11.5±7.2 years KE group: age 29.6±5.8 years; course of disease 10.2±5.7 years	Lack of control of ejaculation and vaginal ejaculation within <1 minute	3-month PRM versus 3-month KE	IELT; PEDT score	IELT after treatment significantly longer than before KE treatment (p=0.001) and performing PRM (p<0.001) Median PEDT score after treatment significantly lower than before KE treatment (p<0.001) and performing PRM (p<0.001)
Kaplan, 1974^34	To explore effectiveness of group treatment for PE	Journal article	Prospective pilot study	4 heterosexual couples	Mean age of men 37.8 years	Ability of a man to tolerate high (plateau) levels of sexual excitement without ejaculating reflexly	Group therapy involving man and his partner with other couples lasting 3–6 weeks. Meet once a week for 6–12 visits plus home-based exercises using Semans approach		Man from couple 1 described a sense of control and awareness of penile sensations. Intercourse now lasted as long as they liked Man from couple 2 gained satisfactory ejaculatory continence by fifth group session Couple 3 reported success had continued; in addition, wife had become orgastic again and no longer worried about sex. Husband reported mild depression had lifted Man from couple 4 had achieved complete ejaculatory control, and frequency of sexual contact was once per week
Kempeneers, 2012^35	To improve the bibliotherapy approach using up-to-date knowledge and techniques	Journal article	Randomised, wait list controlled pilot study	421 although only 392 completed questionnaire and were randomised (n=326 intervention; n=66 wait list control)	Mean age of all participants: 39.1±11.3 years	Ejaculation generally occurred before man wished, with sexual stimulation estimated as minimal before, during, or shortly after penetration	Intervention: received booklet ‘The Practical Guide of PE’ Control: wait list before receiving intervention	Sexual functioning questionnaire; adapted Spielberger's State Anxiety Inventory; SIQ; TCI-R; LSAS; SISST; self-reported feelings of improvement	Significant improvements found for all self-reported parameters, both at 4–8 and at 10–14 months after bibliotherapy. Improvements associated with adjustment of sexual cognitions
Kempeneers, 2017^36	To evaluate possible benefit of offering therapist support for bibliotherapy developed by Kempeneers et al. (2012, 2015)	Journal article	RCT	135, although only 71 completed post-test (n=37 were pure self-help group; n=34 were guided self-help)	Mean age: 37.40±10.24 years Higher educational qualification: 48 (67.61%) Participant with a single partner: 62 (87.32%)	ISSM definition: lifelong PE, defined as a lifelong and generalised PE with latency times of >1 minute	Intervention: received booklet ‘Fighting against Premature Ejaculation: A Practical Guide’ with guidance from a therapist Intervention: received booklet ‘Fighting against Premature Ejaculation: A Practical Guide’ only	Sexual functioning questionnaire; PEP; SIQ; self-reported feelings of improvement; CGIC; self-reported perception of the treatment; WAI	4–8 months post-treatment, improvements in both groups and in each subtype of PE on self-reported measures of sexual functioning and sexual cognitions. Univariate analyses indicated slightly greater treatment effects in guided self-treatment group, but multivariate tests failed to identify a significant effect of therapist support
Kilinc, 2017^37	To determine whether physical activity had favourable effects on PE and to compare its effectiveness with dapoxetine	Journal article	Randomised, sham-controlled trial	105 (n=35 treated with dapoxetine, (30mg) (Group 1), n=35 performed moderate physical activities (Group 2), and n=35 performed minimal physical activity (Group 3-sham)	Group 1: age 28.0±5.0 years; BMI = 27.3±2.8 kg/m^2; MET baseline = 282±179 METs Group 2: age 26.3±4.9 years; BMI = 27.7±2.8kg/m^2; MET baseline = 289±130 METs Group 3: age 27.9±5.0 years; BMI = 27.3±2.7kg/m^2; MET baseline = 266±125 METs	<1 minute considered PE	Group 1: 30 days of dapoxetine 30mg Group 2: advised to undertake moderate running for at least 30 minutes for 5 days/week for 30 days Group 3: advised to walk at most 30 minutes for 5 days in a week to keep in the ‘inactive’ IPAQ classification for 30 days	IELT measured using a stop watch; PEDT score; MET scores	IELT: comparison of three groups and all two-group binary comparisons’ results showed significant differences compared with each other (all p<0.001) Comparing day 30 scores of three groups, and groups 1–3 and groups 2–3 results yielded significant differences (all p<0.001), while difference between groups 1 and 2 was not significant (p=0.73) PEDT score: binary comparisons among three groups showed day 30 scores were significantly smaller than baseline scores in groups 1 and 2, compared with group 3 (p<0.001, p<0.001 and p=0.12 respectively). MET score: all comparisons among three groups and between two study groups showed significant differences on day 30 (p<0.001 for all)
La Pera, 1996^38	To evaluate pelvic floor rehabilitation as possible treatment for PE	Journal article	Longitudinal	18	34 years old (range 20–52 years) 83% of patients had history of PE of at least 5 years’ duration and 66% had previously undergone treatments based on anaesthetic cream, alpha blockers, start-and-stop therapy, and antidepressant tricyclics, without benefit	The inability of a man to tolerate high (plateau) levels of sexual excitement without ejaculating reflexly	Rehabilitation protocol included physiokinesiotherapy of pelvic floor, electrostimulation, and biofeedback The three techniques were applied in the same setting, in three separate weekly sessions, each one lasting 60 minutes. Protocol included completion of 20 consecutive sessions	Ability to control ejaculatory reflex	After treatment, 11 of 18 patients (61%) learned to control the reflex and were considered cured. Two patients slightly improved intercourse time without clinical help. Five did not respond positively to treatment Best results obtained with younger patients Results were maintained at follow-up (6–14 months)
La Pera, 2014^39	To evaluate cure rates in an unselected population of patients with lifelong PE undergoing rehabilitation treatment of pelvic floor who have been taught the role of the pelvic floor and timing of contraction of these muscles	Journal article	Longitudinal	78	41±8 years One patient had hyperthyroidism; all other patients’ hormonal levels were normal Eight patients had a significantly low testosterone	All patients had IELT in <1 minute and a PEDT test score >11	2–6 months, with average of 2–5 visits per cycle, involving rehabilitation of pelvic floor consisting mainly of biofeedback, pelvic exercises and in some cases also electro-stimulation	IELT; PEDT score	43 (55%) patients who completed training were cured of PE A subgroup of 26 patients, IELT went on average from <2 to >10 minutes
Leiblum, 1976^40	To report rationale and results of a 10-session group composed of couples with mixed sexual dysfunctions (including PE)	Journal article	Longitudinal	3	Couple A: 32 years old; duration of PE 3–4 years Couple C: 35 years old; duration of PE 15 years Couple E: 27 years old; duration of PE 7 years	Not specified	Weekly 2-hour, 10-session group therapy	Sexual Interaction Inventory; Locke-Wallace Scale of Marital Adjustment; self-reported current frequency of and satisfaction with sexual encounters	Couple A: Locke-Wallace Scale of Marital Adjustment increased by 16; considerable improvement in quality and quantity of sexual relations; gratified by greater control of ejaculation he achieved using squeeze technique Couple C: Locke-Wallace Scale of Marital Adjustment increased by 1; considerable improvement in quality and quantity of sexual relations Couple E: Locke-Wallace Scale of Marital Adjustment increased by 12; considerable improvement in quality and quantity of sexual relations; squeeze technique worked well for him, and he was able to delay ejaculation for upward of 5 minutes. He no longer avoided sex and felt more confident about his sexual performance
Makwana, 2012^41	To compare effectiveness of yoga and stop-start technique for correcting PE	Journal article	Randomised trial	30 (n=15 for yoga; n=15 for stop-start method)	Aged 30–45 years	DSM-IV criteria and Premature Ejaculation Test	Group A: daily yoga for 30–40 minutes for 3 months Group B: stop-start technique before each sexual act for 3 months	IELT	IELT increased in group A by 51.7±7.72 seconds at post-yoga versus pre-yoga (p<0.05) IELT increased in group B by 23.73±7.76 seconds at post stop-start technique versus pre stop--start technique (p<0.05)
Mamidi, 2013^42	(1) To evaluate efficacy of certain yogic and naturopathic procedures individually in management of PE (2) To compare the efficacy between yogic and naturopathic procedures in management of PE	Journal article	Randomised pilot study	12 (n=6 for yoga group; n=6 for naturopathy group)	Age range 20–60 years	DSM-IV-TR diagnostic criteria of PE (302.75)	Yoga: 3-week intervention with 1-hour session every day Naturopathy: 3-week intervention with two 30-minute sessions every day involving lower abdomen massage and steam bath, hip bath and lingasnana, mud pack on lower abdomen, and acupressure	PESI	After treatment period, percentage of relief on PESI total score was 7.3% (p<0.01) in yoga group and 2.4% in naturopathy group (p>0.05). PESI total score in two treatment groups statistically insignificant (p>0.05)
Mantovani, 2017^43	To test therapeutic viability of dynamic rehabilitative/behavioural therapy compared with pharmacological treatment	Journal article	Prospective pilot study	18 (n=6 for pharmacological treatment; n=6 for dynamic rehabilitative treatment; n=6 for combination treatment)	Aged between 25 and 55 years (mean: 40 years), all with primary PE, free of comorbidities and with partners involved	Not clearly specified; seemingly <1 minute considered PE	Group A: 30mg dapoxetine before sexual relations for 3 months Group B: 3 months of dynamic rehabilitative treatment consisting of daily physiotherapy, extracorporeal magnetic innervation followed by functional electrical stimulation and biofeedback. Couples also trained in home behavioural therapy Group C: combination of both	PEDT score; IELT	Group A, 75% of patients cured at 3 months and 25% at 6 months. Group B, 25% of patients cured at 3 months and 25% at 6 months. Group C, 75% of patients cured at 3 months and 50% at 6 months From the baseline to the evaluation at 3 and 6 months, all groups presented a significant (p<0.0001) increase in IELT values and a reduction in PEDT score. In group A, increase in IELT significantly lower compared with group C and similarly decrease in reduction in PEDT scores lower in group A than in group C
Mohammadi, 2013^44	To assess effectiveness of CBT for signs, symptoms, and some of sexual-clinical consequences of having a sexual dysfunction, including sexual esteem, sexual anxiety, sexual depression, sexual fear and sexual satisfaction in a patient with PE	Journal article	Single arm pre- and post-design	15	Iranian Age range 25–40 years (no mean provided) Patients of a psychological service centre	PE defined according to DSM-IV-TR, including short duration to ejaculation, a sense of loss of control of the ejaculation, and considerable distress caused by the disorder	8–12 sessions of CBT; 45–90 minutes per session	Ejaculation latency time and sense of control, measured using Arabic Index of Premature Ejaculation	Significant reduction in: Ejaculation latency time (M –0.83, SD 0.71, p=0.02) Ejaculation control (M –1.0, SD 0.85, p=0.02) Premature ejaculation (total number (M 9.58, SD 2.06, p=0.000)
Namavar, 2011^45	To investigate the effect of removal of prepuce remnants on PE in circumcised adults	Journal article	Single arm pre- and post-design	47	Iranian men suffering from PE who had remnants of foreskin remaining following circumcision Mean age 28.4±0.9 years	Not reported	Remnants of foreskin were surgically removed	PE history, PE history in family changes of intercourse frequency, IELT, partner orgasm frequency, penis and glans sensitivity, control over ejaculation, men and their partners overall satisfaction, and sexual life before and after operation	Significant improvement in: Intercourse (times/week) p=0.035 IELT (seconds) p=0.001 Partner orgasm (times/week) p<0.001 Man satisfaction (unit) p<0.001 Partner satisfaction (unit) p<0.001 Control on ejaculation (unit) p<0.001
Optale, 1998^46	To test effects of psychodynamic psychotherapy integrating virtual reality	Journal article	Before and after study in two different populations	Group 1: 50 Group 2: 16	Group 1: impotent for at least 6 months; mean age 45 years (range 22–75) Group 2: primary premature ejaculation; mean age 31 years (range 21–44)		12 one-hour full-immersion virtual reality as well as psychotherapy sessions over 25 weeks	Self-administered sexual-activity questionnaire	Patients benefiting from the therapy reported lasting improvement when contacted 6 months after the last session
Optale, 2004^47	To evaluate efficiency of combined use of psychodynamic psychotherapy integrating virtual reality for treatment of erectile dysfunction and PE	Journal article	Study 1: controlled trial Study 2: single arm pre- and post- design	Study 1: 30 Study 2: 160	Study 1: not reported Study 2: not reported	Study 1: not reported Study 2: not reported	Intervention group: 12 sessions of psychotherapeutic treatment using Virtual Reality-Optale Method Control group: same as intervention, but used old virtual reality system	IIEF; Hamilton Psychiatric Rating Scale Depression	Study 1: G2 = 2.27 (df 8, p=0.97) Study 2: G2 = 9.84 (df 16, p=0.87)
Optale, 2003^48	Evaluate efficiency, after 1 year, of combined use of psychodynamic psychotherapy integrating virtual reality for the treatment of erectile dysfunction and PE	Journal article	Single arm pre- and post-design	160 (30 PE)	Not reported	DSM-IV definition – symptoms of PE present for at least 6 months	12 one-hour sessions over 25 weeks of psychotherapeutic treatment using virtual reality	IIEF	At 12 months, 54% PE resolved
Optale, 2020^49	To evaluate effects of integrating psychological treatment for PE with a mobile coaching app that offers therapeutic exercises on the patient's smartphone	Journal article	RCT	35	Mean age 34 (SD 9.15) years	‘Meets the diagnostic criteria for lifelong-type PE’	15 sessions (45 minutes) of psychodynamic psychotherapy integrating behavioural therapy using a smartphone app over a 3-month period	IIEF-15 questionnaire; PEDT; PEP; IELT	Compared with treatment as usual: Significant reduction in frequency of patients with no PE (p<0.001 Significantly greater decrease in PEDT score Significant increase in PEP scores Significant effects for intercourse satisfaction and overall satisfaction in IIEF-15
Pastore, 2012^50	To compare effectiveness of 12 weeks of pelvic floor muscle rehabilitation with on-demand SSRI treatment on changes in the IELT	Journal article	RCT	40	Mean age 30.5 years All participants had lifelong PE, with a baseline IELT of ≤60 seconds (mean: 43.2 seconds, range: 24.6–58.8 seconds) and in stable relationship for at least 6 months	ISSM definition of PE	Pelvic floor muscle rehabilitation with modified techniques used to treat urinary and faecal incontinence	IELT	At the end of treatment period, 11 of the 19 patients (57%) treated with rehabilitation were able to control ejaculation reflex At 12 weeks: significant improvement in both groups, but no apparent between-group difference
Pastore, 2014^51	To evaluate effectiveness of pelvic floor muscle rehabilitation by measuring changes in IELT after 12 weeks of therapy	Conference abstract	Prospective study	40	Baseline IELT ≤60 seconds (mean: 31.7 seconds, range: 16.6–57.4 seconds)	ISSM definition of PE	12 weeks pelvic floor muscle rehabilitation	IELT	33 (82.5%) of 40 patients gained control of ejaculation reflex At the end of intervention, mean IELT increased to 146.2±38.3 seconds
Pastore, 2018^52	To evaluate long-term outcomes of pelvic floor muscle rehabilitation in patients suffering from lifelong PE	Conference abstract	Prospective study	154	Not reported	Baseline IELT 60 seconds and PEDT test >11	12 weeks pelvic floor muscle rehabilitation	IELT; PEDT	111 (90.9%) of 122 patients gained control of ejaculation reflex, with mean IELT and PEDT of 161.6 (SD 14.57) seconds and 2.3 (SD 1.1), respectively, at week 12 of pelvic floor muscle rehabilitation
Pavone, 2017^53	To evaluate feasibility of group psychotherapy to treat PE and evaluate efficacy of two different treatments (pharmacological and psychological), either alone or in combination	Journal article	Randomised trial	279	Mean age (years) 45.32 44% married 32% employed	Lifelong PE measured with IELT ≤2 minutes and PEDT >9	Three intervention groups (no control) Group A: treated with dapoxetine Group B: group psychotherapy in 16 weekly sessions of 2 hours each Group C: treated with dapoxetine and group psychotherapy	IELT; PEDT	Group B: reduction in mean PEDT from 13.44 to 5.11 and an increased IELT from 48.33 to 431.11 seconds (p<0.001)
Rodríguez, 2015^54	Desensitising masturbation aid can produce increases in IELT	Journal article	Prospective study	9	Aged between 20 and 43 years	ISSM definition of PE	Use of Tenga Flip masturbation aid 5 times per week for 6 weeks	IELT	IELT increased up to 57% during masturbation and up to 79.9 % during coitus
Rodríguez, 2019^55	To determine efficacy of a new form of CBT called Sphincter Control Training in combination with a masturbation aid device	Journal article	RCT	35	Mean age 33.7 (SD 8.9) years	PEDT >11 and IELT ≤2 minutes	7 weeks of sphincter control training programme, with one group also using a Flip Zeroby masturbation device	PEDT; IELT (fold increase); PEP	Statistically significant difference (p=0.003) in increase experienced by subjects in group with device compared with those without (mean 166.63 [SD 106.54] vs 86.99 [SD 59.98]). Statistically significant differences in fold increase in IELT (p=0.008) between the group with vs without the device (2.69 [1.81] vs 1.38 [0.50])
Rodríguez, 2021^56	To determine effect of a masturbation aid device with a sphincter control training programme compared with sphincter control training alone	Journal article	RCT	50	Mean age 32.76±7.10 years in intervention group and 38.00±7.99 years in control group Mean duration in relationship 8.88±5.76 years in intervention group and 11.60±8.31 years in control group	PEDT ≥11 IELT ≤2 minutes	Both groups participated in an 8-week sphincter control training programme consisting of four different educational and exercise sessions Intervention group also used a Myhixel I masturbation aid	‘Fold increase’ in and mean change in IELT and PEDT	Significant differences between groups in mean IELT (p=0.001) and fold increase in IELT (p=0.001) in intervention group compared with control group Significant improvements in PEDT in both groups
Rodríguez, 2018^57	To determine efficacy of sphincter control training with a masturbation aid device	Conference abstract	RCT	35	Not reported	PEDT ≥11 IELT ≤2 minutes	Both groups participated in a 7-week sphincter control training programme consisting of four different educational and exercise sessions Intervention group also used a Myhixel I masturbation aid	‘Fold increase’ in and mean change in IELT and PEDT	The fold increase of IELT was 2.7 in experimental group number one (exercise and device), and in experimental group number two (exercise) was 1.3 at endpoint
Rodríguez, 2019 ^58	The aim of this study was to determine efficacy and safety of sphincter control training using a medical device designed for treatment	Conference abstract	Case series	10	Not reported	PEDT ≥11 IELT ≤2 minutes	Both groups participated in a 7-week sphincter control training programme consisting of four different educational and exercise sessions Intervention group also used a Myhixel I masturbation aid	‘Fold increase’ in and mean change in IELT and PEDT	Geometric mean average IELT significantly increased in participants from 79.06 seconds at baseline to 216.21 seconds at study endpoint Fold increase average IELT of the 10 participants was 2.89. 6 of 10 participants did not meet criteria for diagnosis of PE at study endpoint
Rohilla, 2020^59	To investigate effect of yoga on ejaculation time in patients with PE and compare with paroxetine	Journal article	Non-randomised trial	68	Mean age intervention group 30.38±4.79 years and control group 31.36±4.77 years	DSM-5 criteria	14-week yoga programme	IELT	Significant increase in IELT in both groups, but no significant difference between groups
Saadat, 2021^60	To evaluate effect of on-demand caffeine consumption on treating patients with PE compared with squeezing technique	Journal article	Non-blind RCT	42	Healthy individuals with PE; mean age 39.48±7.62 years	ISSM 2008 Ejaculation delay that always or nearly always occurs prior to or within 1 minute of vaginal penetration	Caffeine group received 100mg of encapsulated caffeine for 3 weeks, 2 hours prior to each intercourse	IELT and ISS	No significant difference between 2 groups
Sahin, 2016^61	To compare safety and efficacy of dapoxetine and acupuncture for treatment of PE	Journal article	Prospective RCT	120	120 married males (mean age ± SD 33.4±6.2 years) No differences between groups in age, BMI, baseline IELT and PEDT scores	ISSN 2014, ‘ejaculation that always or nearly always occurs prior to or within 1 minute of vaginal penetration from the first sexual experience, or clinically significant reduction in latency time’	For 4 weeks 30 acupuncture 30 sham acupuncture 30 dapoxetine 30mg 30 dapoxetine 60mg	IELT and PEDT	After 4 weeks, IELT significantly longer compared with baseline values in all groups. Dapoxetine 60mg significantly higher than those achieved in all other groups (p<0.001). Dapoxetine 30mg significantly higher than those achieved with acupuncture and sham acupuncture groups Changes with acupuncture significantly higher than with sham acupuncture (p<0.001)
Shechter, 2019^62	To evaluate efficacy and safety of transcutaneous electrical stimulation (TES) for treatment of PE	Journal article	Prospective, single-blinded, self-controlled study	23	23 males generally healthy aged 20–60 years (mean: 38.7) with lifelong PE	International Society for Sexual Medicine 2014, ‘ejaculation that always or nearly always occurs prior to or within 1 minute of vaginal penetration from the first sexual experience, or a clinically significant reduction in latency time’	TES	Masturbation ejaculatory latency time (MELT)	During the active TES treatment mean MELT was significantly longer than sham treatment (311.4±237.14 seconds vs 124.6±107.02 seconds, p=0.0009). This difference represents an averaged time-fold increase of 3.49±3.12 in MELT
Sunay, 2011^63	To determine whether acupuncture is effective as a PE treatment compared with paroxetine and placebo	Journal article	RCT placebo- controlled	Three groups: 30 paroxetine, 30 acupuncture and 30 placebo	Mean ages of groups were similar: 37.5 years (range: 28–47), 40.4 years (range: 30–50) and 38.3 years (range: 28–48) in the paroxetine, acupuncture and placebo groups, respectively. 91.1% (82 of 90) were married	DSM-IV-TR diagnostic criteria of PE	Medicated group received paroxetine 20mg daily; acupuncture or sham-acupuncture (placebo) groups were treated twice a week for 4 weeks	IELT and PEDT	Median PEDT scores of paroxetine, acupuncture and placebo groups were 17.0, 16.0 and 15.5 before treatment and 10.5, 11.0 and 16.0 after treatment, respectively (p=0.001, p=0.001 and p=0.314, respectively) Significant differences found between mean-rank IELTs of paroxetine and placebo groups (p=0.001) and acupuncture and placebo groups (p=0.001) after treatment Increase of IELTs with paroxetine, acupuncture and placebo acupuncture were 82.7, 65.7 and 33.1 seconds, respectively.
Uribe, 2019^64	To evaluate efficacy and safety of transcutaneous posterior tibial nerve stimulation (TPTNS) to treat PE	Journal article	Single-arm clinical trial	11	Patients (median age 30 years, range 21–49) had to be within a stable heterosexual relationship for over 6 months, with intercourse not less than once per week; with no PE treatment during previous 6 months	American Psychiatric Association Diagnostic and Statistical Manual, DSM-5	TPTNS consisted of 30-minute sessions of 20Hz with a pulse amplitude of 200μs Intensity adjusted based on individual sensitivity Participants received 3 sessions per week for 12 consecutive weeks. Follow-up for 9 months after therapy completion	IELT	11 patients completed therapy, and 54.5% (p=0.037) showed tripled baseline IELT scores at week 12. IELT increased 4.8-fold, 6.8-fold and 5.4-fold at weeks 12, 24 and 48, respectively
Ventus, 2019^65	To evaluate effectiveness of vibrator-assisted start–stop exercises for treatment of PE	Journal article	RCT	50 were included and randomised into two treatment groups and a waiting list control group	Age 41.7 years Participants had to be at least 18 years old, understand spoken and written Swedish, ejaculate within 3 minutes after penetration (self-reported), not experience erectile problems that hinder penetrative sex or masturbation, not suffer from multiple sclerosis, and not use medication that may affect ejaculation latency time, such as SSRIs and opioids	American Psychiatric Association Diagnostic and Statistical Manual, DSM-5	Treatment group were instructed to perform start–stop exercises while stimulating the penis with a purpose-made vibrator, three times a week for 6 weeks. Additionally, participants in one of the treatment groups received additional psychoeduation and performed mindfulness meditation-based body scan exercises three times a week	IELT	Interventions reduced PE symptoms with large effect sizes (partial η2 = 0.20 across three groups, d [95% CI] = 1.05 [0.27, 1.82] and 1.07 [0.32, 1.82] for treatment groups compared with waiting list control group). Additional psychobehavioural intervention did not further reduce PE symptoms, but did decrease PE-associated negative symptoms such as levels of sexual distress, anxiety and depression
Wang, 2019^66	To explore a novel surgical treatment for primary PE using an inner condom technique	Journal article	Cohort	20	Average age of the cohort was 33 years (range 18–52 years), with an average course of disease of 12 years (range 1–32 years). Four males were circumcised	Not specified	By surgery, an inner condom made of acellular dermal matrix was transferred to the subcutaneous pocket of the penis. Average follow-up was 6 months (range 2–12 months)	IELT	Surgical intervention significantly increased the average IELT in patients, from 0.67 to 2.37 minutes (p=0.009)
Zhang, 2018^67	To investigate efficacy of acellular dermal matrix in penis augmentation for PE	Journal article	Cohort	39	Mean age at the time of surgery 29 years, range 24–37 They had to have a heterosexual, stable and monogamous sexual relationship with the same partner for at least 6 months	Not specified	By surgery, an inner condom made of acellular dermal matrix was transferred to subcutaneous pocket of penis. Data were collected 6 months and 2 years after operation	IELT	Compared with baseline data, IELT scores were increased, and PE was relieved at 6 months and 2 years after operation Mean self-estimated IELT score increased to 424.3±123.8 seconds at 6 months; to 412.8±123.1 seconds at 2 years (p<0.05)

• Abbreviations: BMI, body mass index; CBT, cognitive behavioural therapy; CGIC, Clinical Global Impression of Change; CHEES, Checklist for Early Ejaculation Symptoms; CPAP, continuous positive airway pressure; IELT, intravaginal ejaculation latency time; IIEF, International Index of Erectile Function; IPAQ, International Physical Activity Questionnaire; ISS, Index of Sexual Satisfaction; ISSM, International Society for Sexual Medicine; KE, Kegel exercise; LSAS, Liebowitz's Social Anxiety Scale; MELT, masturbation ejaculatory latency time; MET, metabolic equivalent; OSAS, obstructive sleep apnoea syndrome; PE, premature ejaculation; PEDT, Premature Ejaculation Diagnostic Tool; PEP, Premature Ejaculation Profile; PESI, definition to follow; PRM, penis-root masturbation; RCT, randomised controlled trial; SD, standard deviation; SIQ, Sexual Irrationality Questionnaire; SISST, Social Interaction Self-Statement Test; SKGB, standardised Korean ginseng berry; SQoL-M, Sexual Quality of Life—Male; SSRI, selective serotonin reuptake inhibitor; TCI-R, Cloninger's Temperament and Character Inventory—Revised; TES, transcutaneous electrical stimulation; TPTNS, transcutaneous posterior tibial nerve stimulation; WAI, Working Alliance Inventory.