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Complementary and Alternative Medicine for Management of Premature Ejaculation: A Systematic Review

Open AccessPublished:December 30, 2016DOI:https://doi.org/10.1016/j.esxm.2016.08.002

      Abstract

      Introduction

      Premature ejaculation (PE) is defined as ejaculation within 1 minute (lifelong PE) or 3 minutes (acquired PE), inability to delay ejaculation, and negative personal consequences. Management includes behavioral and pharmacologic approaches.

      Aim

      To systematically review effectiveness, safety, and robustness of evidence for complementary and alternative medicine in managing PE.

      Methods

      Nine databases including Medline were searched through September 2015. Randomized controlled trials evaluating complementary and alternative medicine for PE were included.

      Main Outcome Measures

      Studies were included if they reported on intravaginal ejaculatory latency time (IELT) and/or another validated PE measurement. Adverse effects were summarized.

      Results

      Ten randomized controlled trials were included. Two assessed acupuncture, five assessed Chinese herbal medicine, one assessed Ayurvedic herbal medicine, and two assessed topical “severance secret” cream. Risk of bias was unclear in all studies because of unclear allocation concealment or blinding, and only five studies reported stopwatch-measured IELT. Acupuncture slightly increased IELT over placebo in one study (mean difference [MD] = 0.55 minute, P = .001). In another study, Ayurvedic herbal medicine slightly increased IELT over placebo (MD = 0.80 minute, P = .001). Topical severance secret cream increased IELT over placebo in two studies (MD = 8.60 minutes, P < .001), although inclusion criteria were broad (IELT < 3 minutes). Three studies comparing Chinese herbal medicine with selective serotonin reuptake inhibitors (SSRIs) favored SSRIs (MD = 1.01 minutes, P = .02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies; MD = 1.92 minutes, P < .00001) and over Chinese medicine alone (two studies; MD = 2.52 minutes, P < .00001). Adverse effects were not consistently assessed but where reported were generally mild.

      Conclusion

      There is preliminary evidence for the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical severance secret cream in improving IELT and other outcomes. However, results are based on clinically heterogeneous studies of unclear quality. There are sparse data on adverse effects or potential for drug interactions. Further well-conducted randomized controlled trials would be valuable.

      Key Words

      Introduction

      Premature ejaculation (PE) in men is characterized by short ejaculatory latency during intercourse. PE can be lifelong (primary; present since first sexual experiences) or acquired (secondary; beginning later).
      • Serefoglu E.C.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An evidence-based unified definition of lifelong and acquired premature ejaculation: report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation.
      The International Society for Sexual Medicine (ISSM; 2014) defines PE as a combination of (i) ejaculation usually occurring within approximately 1 minute of vaginal penetration (for lifelong PE) or a clinically significant decrease in latency time, often to no longer than approximately 3 minutes (for acquired PE); (ii) inability to delay ejaculation; and (iii) negative personal consequences such as distress, bother, frustration, and/or avoidance of sexual intimacy.
      • Serefoglu E.C.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An evidence-based unified definition of lifelong and acquired premature ejaculation: report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation.
      PE also has been defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013) as ejaculation usually occurring within approximately 1 minute of vaginal penetration and before the individual wishes it and causing clinically significant distress.
      American Psychiatric Association
      Diagnostic and statistical manual of mental disorders. 5th ed. text rev.
      Estimating the prevalence of PE is not straightforward because of the difficulty in defining what constitutes clinically relevant PE. Surveys have estimated the prevalence of self-reported early ejaculation as 20% to 30%
      • Laumann E.O.
      • Nicolosi A.
      • Glasser D.B.
      • et al.
      Sexual problems among women and men aged 40–80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors.
      • Laumann E.O.
      • Paik A.
      • Rosen R.C.
      Sexual dysfunction in the United States: prevalence and predictors.
      • Porst H.
      • Montorsi F.
      • Rosen R.C.
      • et al.
      The Premature Ejaculation Prevalence and Attitudes (PEPA) survey: prevalence, comorbidities, and professional help-seeking.
      ; however, these estimates are likely to include men who have some concern about their ejaculatory function but do not meet the current diagnostic criteria for PE.
      • Althof S.E.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).
      It has been suggested that the prevalence of lifelong PE according to the ISSM and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition definitions (with an ejaculatory latency of approximately 1 minute) is unlikely to exceed 4%.
      • Althof S.E.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).
      Men with PE are more likely to report lower levels of sexual functioning and satisfaction and higher levels of personal distress and interpersonal difficulty than men without PE.
      • Rowland D.L.
      • Patrick D.L.
      • Rothman M.
      • et al.
      The psychological burden of premature ejaculation.
      They also might rate their overall quality of life as lower than that of men without PE.
      • Rowland D.L.
      • Patrick D.L.
      • Rothman M.
      • et al.
      The psychological burden of premature ejaculation.
      In addition, their partner's satisfaction with the sexual relationship has been reported to decrease with increasing severity of the condition.
      • Byers E.S.
      • Grenier G.
      Premature or rapid ejaculation: heterosexual couples' perceptions of men's ejaculatory behavior.
      Management of PE can involve a range of interventions. These include systemic drug treatments such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, phosphodiesterase type 5 inhibitors, and analgesics and topical anesthetic creams and sprays that are applied directly to the penis shortly before intercourse.
      • Richardson D.
      • Goldmeier D.
      • Green J.
      • et al.
      Recommendations for the management of premature ejaculation: BASHH Special Interest Group for Sexual Dysfunction.
      • Hatzimouratidis K.
      • Eardley I.
      • Giuliano F.
      • et al.
      Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. European Association of Urology.
      Behavioral therapies also can be useful.
      • Althof S.E.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).
      • Richardson D.
      • Goldmeier D.
      • Green J.
      • et al.
      Recommendations for the management of premature ejaculation: BASHH Special Interest Group for Sexual Dysfunction.
      • Melnik T.
      • Althof S.
      • Atallah A.N.
      • et al.
      Psychosocial interventions for premature ejaculation.
      • Cooper K.
      • Martyn-St James M.
      • Kaltenthaler E.
      • et al.
      Behavioral therapies for management of premature ejaculation: a systematic review.
      These can include psychosexual or relationship counseling for men and/or couples to address psychological and interpersonal issues that could be contributing to PE. Behavioral therapies also can include physical techniques to help men develop sexual skills to delay ejaculation and improve sexual self-confidence, such as the “stop-start” technique, “squeeze” technique, and sensate focus.
      • Althof S.E.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).
      • Richardson D.
      • Goldmeier D.
      • Green J.
      • et al.
      Recommendations for the management of premature ejaculation: BASHH Special Interest Group for Sexual Dysfunction.
      • Melnik T.
      • Althof S.
      • Atallah A.N.
      • et al.
      Psychosocial interventions for premature ejaculation.
      • Cooper K.
      • Martyn-St James M.
      • Kaltenthaler E.
      • et al.
      Behavioral therapies for management of premature ejaculation: a systematic review.
      There are sparse data on whether and for how long effectiveness is maintained after cessation of treatment (drug or behavioral) and whether repeat treatments are effective.
      Many interventions currently used for PE are not approved for this use, and men might choose to self-treat, with several remedies being available through the internet. Some complementary and alternative medicines (CAMs) have been evaluated in randomized controlled trials (RCTs) for the management of PE. However, there are no existing systematic reviews evaluating CAMs for management of PE. Our aim was to systematically review the effectiveness, safety, and robustness of evidence for CAM therapies in the management of PE.

      Methods

       Review Methods

      This work was undertaken as part of a systematic review for the UK National Institute for Health Research Health Technology Assessment Programme, which assessed a wide range of interventions for management of PE.
      • Cooper K.
      • Martyn-St James M.
      • Kaltenthaler E.
      • et al.
      Interventions to treat premature ejaculation: a systematic review short report.
      The review followed the general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (http://www.prisma-statement.org/).
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      The review protocol is available from the Health Technology Assessment Programme website (http://www.nets.nihr.ac.uk/projects/hta/131201) and is registered on the PROSPERO database (registration number CRD42013005289). The PRISMA checklist is provided in Supplementary Appendix 3.

       Definition of CAM

      CAM has been defined by the Cochrane Collaboration as “a broad domain of healing resources that encompasses all health systems, modalities, and practices and their accompanying theories and beliefs, other than those intrinsic to the politically dominant health system of a particular society or culture in a given historical period.”
      • Wieland L.S.
      • Manheimer E.
      • Berman B.M.
      Development and classification of an operational definition of complementary and alternative medicine for the Cochrane collaboration.
      In addition, many CAM therapies are based on a traditional model of health and well-being, and many (although not all) are designed to treat the whole patient as opposed to a specific condition, whereas some (although not all) involve the use of traditional or natural therapies. Therefore, CAM is defined in this study as therapies for PE that have typically not been provided within conventional Western health care systems and that appear on the list of CAM therapies collated by the Cochrane Collaboration.
      • Wieland L.S.
      • Manheimer E.
      • Berman B.M.
      Development and classification of an operational definition of complementary and alternative medicine for the Cochrane collaboration.

       Literature Searches

      The following databases were searched from inception to September 2015: Medline; Embase; Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Cochrane Library including the Cochrane Systematic Reviews Database (CDSR), the Cochrane Controlled Trials Register (CCRT), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment database; the ISI Web of Science including the Science Citation Index and the Conference Proceedings Citation Index–Science. The Medline search strategy is provided in Appendix 1. The search strategy was designed to identify any articles tagged with the Medical Subject Headings ejaculation or premature ejaculation plus articles whose title or abstract included one of the terms premature, early, or rapid within three words of ejaculation or climax or the term ejaculation praecox/precox. These were combined with search filters to identify RCTs, reviews, and guidelines. It should be noted that the search was undertaken as part of a wider project assessing different treatments for PE,
      • Cooper K.
      • Martyn-St James M.
      • Kaltenthaler E.
      • et al.
      Interventions to treat premature ejaculation: a systematic review short report.
      and for this reason the search was not specific to complementary therapies. The US Food and Drug Administration website and the European Medicines Agency website also were searched. Existing systematic reviews and relevant studies also were checked for eligible studies.

       Eligibility Criteria

      RCTs were eligible for inclusion if they compared CAM therapies for management of PE against placebo, waitlist, no treatment, or another therapy or assessed combination treatment. CAM is defined as therapies for PE that have typically not been provided within conventional Western health care systems and that appear on the list of CAM therapies collated by the Cochrane Collaboration.
      • Wieland L.S.
      • Manheimer E.
      • Berman B.M.
      Development and classification of an operational definition of complementary and alternative medicine for the Cochrane collaboration.
      Studies were included if they reported intravaginal ejaculatory latency time (IELT) and/or any of the following PE outcome measurements:
      • Premature Ejaculation Profile (PEP)
        • Patrick D.L.
        • Giuliano F.
        • Ho K.F.
        • et al.
        The Premature Ejaculation Profile: validation of self-reported outcome measures for research and practice.
      • Index of Premature Ejaculation (IPE)
        • Althof S.
        • Rosen R.
        • Symonds T.
        • et al.
        Development and validation of a new questionnaire to assess sexual satisfaction, control, and distress associated with premature ejaculation.
      • Premature Ejaculation Diagnostic Tool (PEDT)
        • Symonds T.
        • Perelman M.A.
        • Althof S.
        • et al.
        Development and validation of a premature ejaculation diagnostic tool.
      • Arabic Index of Premature Ejaculation (AIPE)
        • Arafa M.
        • Shamloul R.
        Development and evaluation of the Arabic Index of Premature Ejaculation (AIPE).
      • Chinese Index of Premature Ejaculation–5 (CIPE-5)
        • Yuan Y.M.
        • Xin Z.C.
        • Jiang H.
        • et al.
        Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation.
      • International Index of Erectile Function (IIEF)
        • Rosen R.C.
        • Riley A.
        • Wagner G.
        • et al.
        The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
      Five of these measurements (PEP, IPE, PEDT, AIPE, and CIPE) were referenced in the update of the ISSM PE guidelines.
      • Althof S.E.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).
      Of these, PEP and IPE have been validated as tools to measure changes in PE outcomes,
      • Patrick D.L.
      • Giuliano F.
      • Ho K.F.
      • et al.
      The Premature Ejaculation Profile: validation of self-reported outcome measures for research and practice.
      • Althof S.
      • Rosen R.
      • Symonds T.
      • et al.
      Development and validation of a new questionnaire to assess sexual satisfaction, control, and distress associated with premature ejaculation.
      and CIPE also has been evaluated as a PE outcome measurement.
      • Yuan Y.M.
      • Xin Z.C.
      • Jiang H.
      • et al.
      Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation.
      The PEDT and AIPE have been validated as tools for diagnosing PE
      • Symonds T.
      • Perelman M.A.
      • Althof S.
      • et al.
      Development and validation of a premature ejaculation diagnostic tool.
      • Arafa M.
      • Shamloul R.
      Development and evaluation of the Arabic Index of Premature Ejaculation (AIPE).
      and have been used as outcome measurements in PE trials. In addition, the IIEF was validated for measuring changes in outcomes in erectile dysfunction, but some dimensions overlap with PE and have been used to measure outcomes in PE studies.
      • Rosen R.C.
      • Riley A.
      • Wagner G.
      • et al.
      The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
      Adverse effects also were summarized. Poorly defined outcomes, such as “percentage of patients showing improvement,” were not included in this review.

       Data Extraction and Synthesis

      One reviewer performed data extraction of each study; all numerical data were checked by a second reviewer. Results were presented as forest plots where data permitted, and meta-analyses were undertaken using RevMan software.

      Cochrane Collaboration Review Manager (RevMan). London: Cochrane Collaboration; 2012.

      Assessment of publication bias by visual inspection of funnel plots was planned when at least 10 RCT comparisons were available.
      Cochrane Collaboration
      Cochrane handbook for systematic reviews of interventions version 5.1.0.

       Assessment of Methodologic Quality of Studies

      Methodologic quality of included RCTs was assessed using the Cochrane Collaboration risk-of-bias assessment criteria.
      • Higgins J.P.T.
      • Altman D.G.
      • Sterne J.A.C.
      on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group
      Assessing risk of bias in included studies.
      Completeness of outcome data was considered low risk if the percentage of randomized participants excluded from the primary analysis was smaller than 30%.
      • Wright C.C.
      • Sim J.
      Intention-to-treat approach to data from randomized controlled trials: a sensitivity analysis.
      Selective reporting was considered low risk if IELT or ejaculatory latency was reported and all outcomes referred to in the study methods were reported. Overall risk of bias for each study was classed as “low” or “high” if they were rated as such for each of three key domains: allocation concealment, blinding of outcome assessment, and completeness of outcome data; otherwise, overall risk of bias was classed as “unclear.”

      Results

       Quantity of Evidence

      The searches identified 2,455 citations (as part of a wider project assessing different treatments for PE). Fourteen studies were examined at the full-text stage. Ten RCTs evaluating a complementary therapy for PE were included in the review.
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      The PRISMA flowchart is presented in Appendix 2. The four studies excluded at the full-text stage are described below, with reasons for exclusion.

       Characteristics of Included Studies

      Details of the included study characteristics are presented in Table 1; details include specific acupuncture points and herbal remedies used. Two studies (one in Turkey
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      and one in China
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      ) assessed acupuncture provided daily for 4 weeks and twice weekly for 4 weeks, respectively. Each study used a set range of acupuncture points (with some overlap but some differences between studies). Five studies assessed a 2- to 8-week course of oral Chinese herbal medicine; all were conducted in China.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      One study conducted in India assessed Ayurvedic medicine (Indian herbal medicine) given for 2 months.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      Two Korean studies assessed four to five treatments with “severance secret” (SS) cream,
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      an extract of nine natural products that is applied to the penis 1 hour before intercourse and washed off before intercourse. SS cream is believed to work by localized desensitizing effects to decrease penile hypersensitivity.
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      Table 1Characteristics of included studies
      Study; country; center, nDuration (n), IELT assessmentTreatments and comparatorsCAM treatment detailsPE definitionLifelong and acquired
      Acupuncture
       Sunay et al,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      2011; Turkey; 1
      4 wk (n = 90, a = 90), stopwatchAcupuncture 2×/wk; paroxetine 20 mg/d; sham acupuncture 2× weeklyAcupuncture 2×/wk using points Zusanli (ST 36), Hegu (LI 4), Taixi (KI 3), Taichong (LR 3), Yintang (EX-HN 3), Zhongji (CV 3)IELT ≤ 2 min in >70% of attemptsLifelong 66%, acquired 34%
       Chen,
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      2009; China; 1
      4 wk (n = 111, a = 111), method NRAcupuncture daily; citalopram 20 mg/dAcupuncture: 2 groups of acupoints on alternate days: day 1, Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23); day 2, Guanyuan (CV 4), Zhongji (CV 3), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3)NRNR
      Chinese herbal medicine
       Li and Lu,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      2015; China; 1
      4 wk (n = 120, a = 119), stopwatchChinese medicine (Qilin pills) 6 g 2×/d; sertraline 50 mg/d; Chinese medicine + sertralineChinese medicine (Qilin pills) containing Chinese raspberry (fu pen zi), horny goat weed (yin yang huo), Polygonum multiflorum (he shou wu), Herba ecliptae (mo han lian), Cynomonium (suo yang), Astralagus (huang qi), Chinese yam (shan yao), immature tangerine peel (qing pi), mulberry fruit spike (sang shen), turmeric tuber (yu jin), Chinese red sage (dan shen), white peony root (bai shao)IELT < 1 min in >50% of attempts + TCM definition of “secondary non-consolidated kidney qi PE”Acquired (≥3 mo)
       Xu et al,
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      2014; China; 1
      8 wk (n = 218, a = 200), stopwatchChinese medicine (mycelium of Cordyceps sinensis C4); sertraline 50 mg/dChinese medicine (mycelium of Cordyceps sinensis C4)IELT ≤ 2 min in ≥75% of attemptsAcquired and lifelong (n = NR)
       Xu et al,
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      2012; China; 1
      4 wk (n = 68, a = 68), method NRChinese medicine (Yimusake 50 mg/d); Chinese medicine + trazodone 50 mg/dChinese medicine (Yimusake 50 mg/d)IELT < 2 minLifelong
       Sun et al,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      2010; China; 2
      4 wk (n = 114, a = 114), method NRChinese medicine (Yimusake 1.5 g/d); fluoxetine 20 mg/d; Chinese medicine + fluoxetineChinese medicine (Yimusake 1.5 g/d)IELT < 2 minNR
       Song et al,
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      2007; China; 2
      15 d (n = 68, a = 68), questionnaireChinese medicine (Uighur) 2×/d; treatment as usualChinese medicine (Uighur) 2×/dIELT ≤ 2 min, partner satisfaction < 50%Acquired and lifelong (n = NR)
      Ayurvedic herbal medicine
       Kulkarni and Chandola,
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      2013; India; 1
      2 mo (n = 55, a = 50), method NRAyurvedic herbal medicine 2×/d + psychological counseling; placebo + psychological counselingAyurvedic herbal medicine 2×/d: Stambhanakaraka Yoga containing Tulsi beeja (Occimum santum Linn), Akarakarabha (Anacyclus pyrethrum Linn), Mishri (sugar)IELT ≤ 1 min, partner satisfaction < 50%Acquired and lifelong (n = NR)
      Topical herbal SS cream
       Choi et al,
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      2000; Korea; 3 (crossover)
      5 applications (n = 125, a = 106), stopwatchSS cream (0.20 g applied 1 h before intercourse); placeboSS cream: extracts of 9 natural products applied to glans penis 1 h before intercourse and then washed off (Ginseng radix alba, Angelicae gigantis radix, Cistanches herba, Zanthoxyli fructus, Torlidis semen, Asiasari radix, Caryophylli flos, Cinnamomi cortex, Bufonis venenum)IELT < 3 min AND patient and partner satisfaction <30%Lifelong
       Choi et al,
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      1999; Korea; 1 (crossover)
      4 applications (1 of each dose; n = 73, a = 50), stopwatchSS cream (0.05, 0.10, 0.15, or 0.20 g applied 1 h before intercourse); placeboSS cream: extracts of 9 natural products as aboveIELT < 3 min and/or patient satisfaction < 50%Lifelong
      a = analyzed number; CAM = complementary and alternative medicine; IELT = intravaginal ejaculatory latency time; n = randomized number; NR = not reported; PE = premature ejaculation; SS = secret severance; TCM = traditional Chinese medicine.
      The number of analyzed participants was 50 to 200 for all studies, with the mean and median numbers being 98. Comparators included placebo (four studies),
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      treatment as usual (one study),
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      an SSRI (five studies),
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      and/or a combination of CAM and drug treatment (three studies).
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      Nine of the 10 studies assessed IELT
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      : five by stopwatch,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      one by questionnaire,
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      and three did not report the method of IELT assessment.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      Additional outcome measurements reported included the PEDT (three studies)
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      , the CIPE-5 (two studies)
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      , and the IIEF (one study).
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      Three studies included men with lifelong PE,
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      one included men with only acquired PE,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      four included men with lifelong PE and men with acquired PE,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      and two did not report this information.
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      Participants had an IELT no longer than 1 minute (most or all the time) in two studies,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      an IELT no longer than 2 minutes (most or all the time) in five studies,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      an IELT no longer than 3 minutes in two studies,
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      and IELT inclusion criteria were not reported in one study.
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      In four studies, patient or partner satisfaction also had to be below 30% or below 50%.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      In some studies, the inclusion criteria were not consistent with the ISSM definition of PE. For example, one study of Chinese herbal medicine recruited men with acquired PE, but they had to have an IELT shorter than 1 minute in at least 50% of attempts
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      (whereas the ISSM widens the definition of acquired PE to IELT ≤ 3 minutes
      • Pei J.T.
      • Shi Z.H.
      An effective combined therapy for simple premature ejaculation.
      ). Also, two studies of SS cream stated that participants had lifelong PE but were required only to have an IELT shorter than 3 minutes (plus patient or partner satisfaction below 30% or 50%)
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      rather than no longer than 1 minute according to the ISSM definition of lifelong PE.
      • Althof S.E.
      • McMahon C.G.
      • Waldinger M.D.
      • et al.
      An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).

       Studies Excluded at Full-Text Stage

      Four studies were excluded at the full-text stage. Two studies of Chinese medicine were excluded because they did not report on IELT or any validated or widely used PE outcome measurement.
      • Pei J.T.
      • Shi Z.H.
      An effective combined therapy for simple premature ejaculation.
      • Zhang F.B.
      • Tian Y.
      • Du L.D.
      Xuanju compound capsule combined with erogenous focus exercise is effective for premature ejaculation.
      Two studies assessing a combination of yoga and pelvic floor exercises were excluded; one was not randomized (patients self-selected to the intervention or control group)
      • Dhikav V.
      • Karmarkar G.
      • Gupta M.
      • et al.
      Yoga in premature ejaculation: a comparative trial with fluoxetine.
      and the other did not report on IELT or any validated or widely used PE outcome measurement.
      • Mamidi P.
      • Gupta K.
      Efficacy of certain yogic and naturopathic procedures in premature ejaculation: a pilot study.

       Risk of Bias in Included Studies

      The risk of bias within included studies is presented in Table 2. Five studies reported the method of randomization,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      whereas the other five did not report the method but did state that the study was randomized. Allocation concealment was unclear in all studies. Blinding of participants and personnel was reported as being undertaken in five studies.
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      Blinding of outcome assessment was unclear in all studies except one,
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      which reported that this was blinded. All studies except one
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      were considered at low risk of bias for completeness of outcome data, with eight studies including at least 90% of randomized patients in the primary analysis and the two studies of SS cream including 85%
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      and 68%,
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      respectively. All studies scored a low risk for selective reporting except for one that did not report on IELT.
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      Of the nine studies reporting on IELT, this was measured by stopwatch in five studies,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      by questionnaire in one study,
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      and the method of IELT assessment was not reported in three studies.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      In summary, all 10 studies were classed as having an overall unclear risk of bias because of unclear reporting of allocation concealment (all 10 studies) and unclear blinding of participants and personnel (five studies).
      Table 2Risk of bias in included studies
      RCT; countryRisk of bias
      Random sequence generationAllocation concealmentBlinding of participants and personnelBlinding of outcome assessmentCompleteness of outcome data
      Completeness of outcome data was classed as low risk if fewer than 30% randomized participants were excluded from the primary analysis.
      (n/N, % included in primary analysis)
      Selective reporting
      Selective reporting was classified as low risk if IELT or ejaculatory latency was reported and all outcomes referred to in study methods were reported.
      Overall risk
      Overall risk of bias was classified as low or high if rated as such for each of three key domains: allocation concealment, blinding of outcome assessment, and completeness of outcome data; otherwise, overall risk of bias was classed as unclear.
      Acupuncture
       Sunay et al,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      2011; Turkey
      LowUnclearLow (partial blinding)UnclearLow (90/90, 100%)LowUnclear
       Chen,
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      2009; China
      UnclearUnclearHighUnclearLow (111/111, 100%)High (no IELT)Unclear
      Chinese herbal medicine
       Li and Lu,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      2015; China
      LowUnclearHighUnclearLow (119/120, 99%)LowUnclear
       Xu et al,
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      2014; China
      LowUnclearLowUnclearLow (200/218, 92%)LowUnclear
       Xu et al,
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      2012; China
      UnclearUnclearHighUnclearLow (68/68, 100%)LowUnclear
       Sun et al,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      2010; China
      UnclearUnclearHighUnclearLow (114/114, 100%)LowUnclear
       Song et al,
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      2007; China
      LowUnclearHighUnclearLow (68/68, 100%)LowUnclear
      Ayurvedic herbal medicine
       Kulkarni and Chandola,
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      2013; India
      UnclearUnclearLowUnclearLow (50/55, 91%)LowUnclear
      Topical herbal SS cream
       Choi et al,
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      2000; Korea
      UnclearUnclearLowUnclearLow (106/125, 85%)LowUnclear
       Choi et al,
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      1999; Korea
      LowUnclearLowLowHigh (50/73, 68%)LowUnclear
      IELT = intravaginal ejaculatory latency time; SS = secret severance.
      Completeness of outcome data was classed as low risk if fewer than 30% randomized participants were excluded from the primary analysis.
      Selective reporting was classified as low risk if IELT or ejaculatory latency was reported and all outcomes referred to in study methods were reported.
      Overall risk of bias was classified as low or high if rated as such for each of three key domains: allocation concealment, blinding of outcome assessment, and completeness of outcome data; otherwise, overall risk of bias was classed as unclear.

       Assessment of Effectiveness and Safety

      Effectiveness results are presented in Table 3 and adverse effects are presented in Table 4. Further details of effectiveness (including results data per study group) are presented in Table 5.
      Table 3Effectiveness results
      Studies, nTreatmentComparatorDurationReferenceOutcomeParticipants, nMD (95% CI), P valueFavors
      Acu vs placebo
       1Acu 2x/wkSham acu4 wkSunay 2011
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      IELT (stopwatch)

      PEDT
      60

      60
      MD = 0.55 (NR), .001

      MD = NR (NR), .001
      Acu over sham

      Acu over sham
      Acu vs drug
       2Acu 2x/wkParoxetine 20 mg/d4 wkSunay 2011
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      IELT (stopwatch)

      PEDT
      60

      60
      MD = −0.28 (NR), .001

      MD = NR (NR), NS
      Drug over acu

      Not sig (acu vs drug)
      Acu dailyCitalopram 20 mg/d4 wkChen 2009
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      CIPE-5111MD = 1.44 (0.02 to 2.86), .05Acu over drug
      CM vs TAU
       1CM (Uighur 2x/d)TAU15 dSong 2007
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      IELT (questionnaire)

      CIPE-5
      68

      68
      MD = 1.57 (1.11 to 2.03), .00001

      MD = 4.95 (3.34 to 6.56), .00001
      CM over TAU

      CM over TAU
      CM vs drug
       3CM (Qilin pills 6 g 2x/d)Sertraline 50 mg/d4 wkLi 2015
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      IELT (stopwatch)

      PEDT
      79

      79
      MD = −0.64 (−1.58 to 0.30), .18

      MD = −0.20 (−0.97 to 0.57), .61
      Not sig (drug vs CM)

      Not sig (drug vs CM)
      CM (mycelium of cordyceps sinensis C4)Sertraline 50 mg/d8 wkXu 2014
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      IELT (stopwatch)

      PEDT
      200

      200
      MD = −1.70 (−2.12 to −1.28), <.01

      MD = −3.8 (−5.01 to −2.59), <.01
      Drug over CM

      Drug over CM
      CM (Yimusake 1.5 g/d)Fluoxetine 20 mg/d4 wkSun 2010
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      IELT (method NR)

      Satisfaction (IIEF)
      76

      76
      MD = −0.60 (−1.01 to −0.19), .004

      MD = −0.90 (−1.43 to −0.37), .0009
      Drug over CM

      Drug over CM
      CM + drug vs drug alone
       2CM (Qilin) + sertralineSertraline 50 mg/d4 wkLi 2015
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      IELT (stopwatch)

      PEDT
      79

      79
      MD = 2.05 (0.83 to 3.27), .001

      MD = 1.10 (0.46 to 1.74), .0008
      Combined over drug

      Combined over drug
      CM (Yimusake) + fluoxetineFluoxetine 20 mg/d4 wkSun 2010
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      IELT (method NR)

      Satisfaction (IIEF)
      76

      76
      MD = 1.90 (1.47 to 2.33), <.00001

      MD = 3.00 (2.46 to 3.54), <.00001
      Combined over drug

      Combined over drug
      CM + drug vs CM alone
       3CM (Qilin) + sertralineCM (Qilin 6 g 2x/d)4 wkLi 2015
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      IELT (stopwatch)

      PEDT
      80

      80
      MD = 2.69 (1.57 to 3.81), <.00001

      MD = 1.30 (0.63 to 1.97), .0001
      Combined over CM

      Combined over CM
      CM (Yimusake) + fluoxetineCM (Yimusake 1.5 g/d)4 wkSun 2010
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      IELT (method NR)

      Satisfaction (IIEF)
      76

      76
      MD = 2.50 (2.08 to 2.92), <.00001

      MD = 3.90 (3.32 to 4.48), <.00001
      Combined over CM

      Combined over CM
      CM (Yimusake 50 mg/d) + trazodone 50 mg/dCM (Yimusake 50 mg/d)4 wkXu 2012
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      IELT (method NR)68MD = 0.08 (−0.19 to 0.35), .56Not sig (combined vs. CM)
      Ayurvedic herbal medicine vs placebo
       1Ayurvedic med + counsellingPlacebo + counselling2 moKulkarni 2013
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      IELT (method NR)50MD = 0.80 (0.32 to 1.28), .001Ayurveda + counselling over placebo + counselling
      Topical herbal SS cream vs placebo
       2SS cream (0.2 g/h prior)Placebo (crossover)5 appChoi 2000
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      IELT (stopwatch)106MD = 8.47 (6.52 to 10.42), <.001SS cream over placebo
      SS cream (0.2 g/h prior)Placebo (crossover)1 appChoi 1999
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      IELT (stopwatch)50MD = 8.79 (6.41 to 11.17), <.001SS cream over placebo
      Acu = acupuncture; app = applications; CI = confidence interval; CIPE = Chinese Index of Premature Ejaculation; CM = Chinese medicine; IELT = intra-vaginal ejaculatory latency time; IIEF = International Index of Erectile Function; MD = mean difference; NR = not reported; PEDT = Premature Ejaculation Diagnostic Tool; TAU = treatment as usual.
      Table 4Adverse effects
      Study, country, duration (n)TreatmentsAEs
      Acupuncture
       Sunay et al,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      2011, Turkey, 4 wk (n = 90, a = 90)
      Acupuncture 2×/wk, paroxetine 20 mg/d, sham acupuncture 2×/wkNo AEs observed (although no formal evaluation of AEs)
       Chen,
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      2009, China, 4 wk (n = 111, a = 111)
      Acupuncture daily, citalopram 20 mg/dNR
      Chinese herbal medicine
       Li and Lu,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      2015, China, 4 wk (n = 120, a = 119)
      CM (Qilin pills 6 g 2×/d), sertraline 50 mg/d, CM + sertralineCM: no AEs reported

      Sertraline: mild transient AEs (gastrointestinal discomfort in 3, headache and dizziness in 2); 1 patient receiving only sertraline discontinued because of erectile dysfunction
       Xu et al,
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      2014, China, 8 wk (n = 218, a = 200)
      CM (mycelium of Cordyceps sinensis C4), sertraline 50 mg/dCM: 7/61 (11.5%) developed mild AEs (dizziness in 2, decreased libido in 1, gastrointestinal discomfort in 4), no discontinuations

      Sertraline: 52/157 (33.1) developed mild AEs (dizziness in 30, decreased libido in 12, other); 3/157 (1.9%) discontinued because of severe dizziness
       Xu et al,
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      2012, China, 4 wk (n = 68, a = 68)
      CM (Yimusake 50 mg/d), CM + trazodone 50 mg/dCM alone: no AEs

      CM + trazodone: minor AEs (headache in 2, dry mouth in 1, constipation in 1)
       Sun et al,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      2010, China, 4 wk (n = 114, a = 114)
      CM (Yimusake 1.5 g/d), fluoxetine 20 mg/d, CM + fluoxetineNumber of AEs with CM + fluoxetine were not significantly different from CM or fluoxetine alone (included nausea, dizziness, headache, flushing, somnolence)
       Song et al,
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      2007, China, 15 d (n = 68, a = 68)
      CM (Uighur) 2×/d, treatment as usualNR
      Ayurvedic herbal medicine
       Kulkarni and Chandola,
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      2013, India, 2 mo (n = 55, a = 50)
      Ayurvedic medicine + counseling, placebo + counselingNR
      Topical herbal SS cream
       Choi et al,
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      2000, Korea, 6 applications (n = 125, a = 106)
      SS cream (0.20 g 1 h before intercourse), placeboSS cream: mild burning sensation in 15% of applications, mild pain in 4% of applications, effects resolved < 1 h
       Choi et al,
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      1999, Korea, 4 applications (n = 73, a = 50)
      SS cream (0.05, 0.10, 0.15 or 0.20 g 1 h before intercourse), placeboSS cream: mild burning sensation in 15% of applications, mild pain in 0.04% of applications
      a = number analyzed; AE = adverse effect; CM = Chinese medicine; n = number randomized; NR = not reported; SS = secret severance.
      Table 5Effectiveness results including results per group
      Study, countryTreatmentComparatorDurationOutcomeParticipants analyzed, nResults per group, mean (SD)MD (95% CI), P valueFavors
      Acupuncture vs placebo
       Sunay et al,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      2011, Turkey
      Acu 2×/wkSham acu4 wkIELT (stopwatch)

      PEDT
      60acu: 1.10 (NR), sham acu: 0.55 (NR)
      Mean change from baseline.


      acu: −4.0, sham acu: 0.0
      Median change from baseline.
      0.55 (NR), .001

      NR (NR), .001
      Acu over sham

      Acu over sham
      Acupuncture vs drug
       Sunay et al,
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      2011, Turkey
      Acu 2×/wkParoxetine 20 mg/d4 wkIELT (stopwatch)

      PEDT
      60acu: 1.10 (NR), paroxetine: 1.38 (NR)
      Mean change from baseline.


      acu: −4.0, paroxetine: −5.0
      Median change from baseline.
      −0.28 (NR), .001

      NR (NR), NS
      Drug over acu

      Acu vs drug NS
       Chen,
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      2009, China
      Acu dailyCitalopram 20 mg/d4 wkCIPE-5111acu: 12.56 (3.84), citalopram: 11.12 (3.77)
      Mean after treatment.
      1.44 (0.02–2.86), .05Acu over drug
      CM vs TAU
       Song et al,
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      2007, China
      CM (Uighur 2×/d)TAU15 dIELT (questionnaire)

      CIPE-5
      68CM: 2.73 (1.25), TAU: 1.16 (0.58)
      Mean after treatment.


      CM: 15.80 (3.60), TAU: 10.85 (3.18)
      Mean after treatment.
      1.57 (1.11–2.03), <.00001

      4.95 (3.34–6.56), <.00001
      CM over TAU

      CM over TAU
      CM vs drug
       Li and Lu,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      2015, China
      CM (Qilin pills 6 g 2×/d)Sertraline 50 mg/d4 wkIELT (stopwatch)

      PEDT
      79CM: 3.23 (1.84), sertraline: 3.87 (2.43)
      Mean after treatment.


      CM: 5.1 (1.8), sertraline: 4.9 (1.7)
      Mean after treatment.
      −0.64 (−1.58 to 0.30), .18

      −0.20 (−0.97 to 0.57), .61
      CM vs drug NS

      CM vs drug NS
       Xu et al,
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      2014, China
      CM (mycelium of Cordyceps sinensis C4)Sertraline 50 mg/d8 wkIELT (stopwatch)

      PEDT
      200CM: 1.4 (0.7), sertraline: 3.1 (2.3)
      Mean after treatment.


      CM: 14.8 (3.5), sertraline: 11.0 (4.9)
      Mean after treatment.
      −1.70 (−2.12 to −1.28), <.01

      −3.8 (−5.01 to −2.59), <.01
      Drug over CM

      Drug over CM
       Sun et al,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      2010, China
      CM (Yimusake 1.5 g/d)Fluoxetine 20 mg/d4 wkIELT (method NR)

      satisfaction (IIEF)
      76CM: 5.2 (0.87), fluoxetine: 5.8 (0.94)
      Mean after treatment.


      CM: 10.3 (1.26), fluoxetine: 11.2 (1.09)
      Mean after treatment.
      −0.60 (−1.01 to −0.19), .004

      −0.90 (−1.43 to −0.37), .0009
      Drug over CM

      Drug over CM
      CM + drug vs drug alone
       Li and Lu,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      2015, China
      CM (Qilin pills) + sertraline 50 mg/dSertraline 50 mg/d4 wkIELT (stopwatch)

      PEDT
      79CM + sertraline: 5.92 (3.11), sertraline: 3.87 (2.43)
      Mean after treatment.


      CM + sertraline: 3.8 (1.2), sertraline: 4.9 (1.7)
      Mean after treatment.
      2.05 (0.83–3.27), .001

      1.10 (0.46–1.74), .0008
      Combined over drug

      Combined over drug
       Sun et al,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      2010, China
      CM (Yimusake) + fluoxetine 20 mg/dFluoxetine 20 mg/d4 wkIELT (method NR)

      satisfaction (IIEF)
      76CM + fluoxetine: 7.7 (0.98), fluoxetine: 5.8 (0.94)
      Mean after treatment.


      CM + fluoxetine: 14.2 (1.31), fluoxetine: 11.2 (1.09)
      Mean after treatment.
      1.90 (1.47–2.33), <.00001

      3.00 (2.46–3.54), <.00001
      Combined over drug

      Combined over drug
      CM + drug vs CM alone
       Li and Lu,
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      2015, China
      CM (Qilin pills) + sertraline 50 mg/dCM (Qilin pills)4 wkIELT (stopwatch)

      PEDT
      80CM + sertraline: 5.92 (3.11), CM: 3.23 (1.84)
      Mean after treatment.


      CM + sertraline: 3.8 (1.2), CM: 5.1 (1.8)
      Mean after treatment.
      2.69 (1.57–3.81), <.00001

      1.30 (0.63–1.97), .0001
      Combined over CM

      Combined over CM
       Sun et al,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      2010, China
      CM (Yimusake) + fluoxetine 20 mg/dCM (Yimusake)4 wkIELT (method NR)

      satisfaction (IIEF)
      76CM + fluoxetine: 7.7 (0.98), CM 5.2 (0.87)
      Mean after treatment.


      CM + fluoxetine: 14.2 (1.31), CM: 10.3 (1.26)
      Mean after treatment.
      2.50 (2.08–2.92), <.00001

      3.90 (3.32–4.48), <.00001
      Combined over CM

      Combined over CM
       Xu et al,
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      2012, China
      CM (Yimusake) + trazodone 50 mg/dCM (Yimusake)4 wkIELT (method NR)68CM + trazodone: 3.05 (0.60), CM: 2.97 (0.54)
      Mean after treatment.
      0.08 (−0.19 to 0.35), .56Combined vs CM NS
      Ayurvedic herbal medicine vs placebo
       Kulkarni and Chandola,
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      2013, India
      Ayurvedic medicine + counselingPlacebo + counseling2 moIELT (method NR)50Ayurveda: 1.85 (0.91), placebo: 1.05 (0.82)
      Mean change from baseline.
      0.80 (0.32–1.28), .001Ayurveda + counseling over placebo + counseling
      Topical herbal SS cream vs placebo
       Choi et al,
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      2000, Korea (crossover)
      SS cream (0.2 g 1 h before coitus)Placebo5 applicationsIELT (stopwatch)106SS cream: 10.92 (9.78), placebo: 2.45 (2.99)
      Mean after treatment.
      8.47 (6.52–10.42), <.001SS cream over placebo
       Choi et al,
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      1999, Korea (crossover)
      SS cream (0.2 g 1 h before coitus)Placebo1 applicationIELT (stopwatch)50SS cream: 11.06 (8.27), placebo: 2.27 (2.26)
      Mean after treatment.
      8.79 (6.41–11.17), <.001SS cream over placebo
      CIPE-5 = Chinese Index of Premature Ejaculation–5 (higher score = better); CM = Chinese medicine; IELT = intravaginal ejaculatory latency time; IIEF = International Index of Erectile Function (higher score = better); MD = mean difference; NR = not reported; NS = not significant; PEDT = Premature Ejaculation Diagnostic Tool (lower score = better; therefore, signs are reversed when calculating the MD); SS = secret severance; TAU = treatment as usual.
      Mean after treatment.
      Mean change from baseline.
      Median change from baseline.

       Acupuncture

      Two RCTs (one in Turkey
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      and one in China
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      ) assessed acupuncture provided daily for 4 weeks and twice weekly for 4 weeks, respectively. Each study used a standardized range of acupuncture points for all patients. There was some overlap, but also some differences, between the acupuncture points used in the two studies (Table 1). There were no studies of individualized acupuncture treatment (where different points are used per patient based on clinical examination).
      One study compared acupuncture against sham acupuncture (N analyzed = 60) and reported a small but significant improvement in stopwatch-measured IELT for acupuncture over sham (mean difference (MD) = 0.55 minute, P = .001) and a significant improvement in PEDT score (P = .001; Table 3).
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      These two studies showed mixed results when comparing acupuncture against drug treatment with an SSRI (paroxetine or citalopram, each given daily for 4 weeks),
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      with IELT favoring drug treatment in the one study reporting this (N = 60; MD = −0.28, P = .001),
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      a PEDT score showing no significant difference (P value not reported),
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      and a CIPE-5 score favoring acupuncture in the other study (N = 111; P = .05).
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      One study reported that no adverse effects were observed (although there was no formal evaluation of these),
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      and the other study did not report adverse effect data (Table 4).
      • Chen Z.X.
      Control study on acupuncture and medication for treatment of primary simple premature ejaculation.
      In summary, the available data indicate that acupuncture might be slightly more effective than placebo (sham) in treating PE, although this is based on only one study of unclear quality.

       Chinese Herbal Medicine

      Five RCTs (all conducted in China) assessed a 2- to 8-week course of oral Chinese herbal medicine.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      Each study used the same herbal medicine(s) for all patients. There were no studies of individualized Chinese medicine (where different herbs are used per patient based on clinical examination). The specific Chinese medicines used differed among studies. One study used Qilin pills (a combination of herbs; Table 1) at a dose of 6 g twice daily
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      ; one used mycelium of Cordyceps sinensis C4
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      ; two used Yimusake (one at 50 mg/d
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      and one at 1.5 g/d
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      ); and one used Uighur twice daily.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      Results for Chinese medicine are presented in Table 3 and Figures 1 and 2. One study favored Chinese medicine (Uighur) over treatment as usual (N analyzed = 68),
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      reporting significant differences in IELT measured by questionnaire (MD = 1.57 minutes, 95% CI = 1.11–2.03, P < .00001) and CIPE-5 score (P < .00001; Table 3 and Figure 1). Three studies compared Chinese medicine against drug treatment with an SSRI (fluoxetine or sertraline, each given daily for 4–8 weeks).
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      Of these, two studies significantly favored SSRIs over Chinese medicine (mycelium of Cordyceps sinensis C4 or Yimusake) for IELT (one measured by stopwatch) and PEDT and IIEF scores,
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      whereas the third study showed no significant difference in stopwatch-measured IELT or PEDT score between the SSRI and Chinese medicine (Qilin pills; Table 3).
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      A meta-analysis of IELT across all three studies significantly favored drug treatment with SSRIs (total N = 355; pooled MD = 1.01 minutes, 95% CI = 0.18–1.84, P = .02; Figure 1), with a high level of heterogeneity (I2 = 86%, P = .0007).
      Figure thumbnail gr1
      Figure 1Intravaginal ejaculatory latency time for Chinese medicine (CM).
      Figure thumbnail gr2
      Figure 2Intravaginal ejaculatory latency time for Chinese medicine (CM) combined with drug treatment. fluox = fluoxetine; SARI = serotonin antagonist and reuptake inhibitor (trazodone); sert = sertraline; SSRI = selective serotonin reuptake inhibitor; trazo = trazodone.
      Two studies compared Chinese medicine (Qilin pills or Yimusake) plus SSRI (fluoxetine or sertraline) against SSRI alone.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      These studies (total N = 155) significantly favored combination treatment over SSRI alone for IELT (one measured by stopwatch; pooled MD = 1.92 minutes, 95% CI = 1.51–2.32, P < .00001) with low heterogeneity (I2 = 0%, P = .82); PEDT and IIEF scores also favored combination treatment (P < .001 for the two comparisons; Table 3 and Figure 2).
      The same two studies compared Chinese medicine (Qilin pills or Yimusake) plus SSRI (fluoxetine or sertraline) against Chinese medicine alone.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      These studies (total N = 156) significantly favored combination treatment over Chinese medicine alone for IELT (one measured by stopwatch; pooled MD = 2.52, 95% CI = 2.13–2.91, P < .00001) with low heterogeneity (I2 = 0%, P = .76); PEDT and IIEF scores also favored combination treatment (P < .0001 for all comparisons). Results favoring combination treatment over drug or Chinese medicine alone (for IELT and PEDT) remained significant 1 month after treatment ended in the one study reporting this.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      A third study (N = 68) comparing Chinese medicine (Yimusake) plus a serotonin antagonist and reuptake inhibitor (trazodone) against Chinese medicine alone
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      showed no significant difference in IELT (measurement method not reported; MD = 0.08, 95% CI = −0.19 to 0.35, P = .56; Table 3 and Figure 2).
      Four of five studies reported data on adverse effects (Table 4).
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      For patients receiving Chinese medicine alone, two studies reported that no adverse effects were observed (one of Qilin pills 6 g twice daily
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      and one of Yimusake 50 mg/d
      • Xu J.X.
      • Gao G.
      • Xu N.
      • et al.
      Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation.
      ). One study reported adverse effects in 12% of patients receiving mycelium of Cordyceps sinensis C4 (including gastrointestinal discomfort, dizziness, and decreased libido),
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      whereas one study reported that the number of adverse effects did not differ significantly among Chinese medicine alone (Yimusake 1.5 g/d), fluoxetine alone, and combination treatment.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      In summary, across studies of Chinese medicine, one study favored Chinese medicine over treatment as usual.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      A meta-analysis of three studies favored SSRI treatment over Chinese medicine.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      Two studies favored Chinese medicine plus SSRIs over SSRIs alone or Chinese medicine alone.
      • Li J.X.
      • Lu Q.G.
      Efficacy of Qilin pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation.
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.

       Ayurvedic Medicine

      One RCT conducted in India (N analyzed = 50) assessed a 2-month course of Ayurvedic medicine (Indian herbal medicine) plus psychological counseling compared with placebo plus psychological counseling.
      • Kulkarni P.V.
      • Chandola H.
      Evaluation of stambhanakaraka yoga and counseling in the management of shukragata vata (premature ejaculation).
      Ayurvedic medicine showed a small but significant improvement in IELT (measurement method not reported; MD = 0.80 minute, 95% CI = 0.32–1.28, P = .001; Table 3). Adverse effects were not reported.

       SS Cream

      Two crossover RCTs conducted in Korea compared SS cream against placebo.
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      These two RCTs showed significant effects on stopwatch-measured IELT (total N = 156; pooled MD = 8.60 minutes, 95% CI = 7.09–10.10, P < .001) with low heterogeneity (I2 = 0%, P = .84; Table 3 and Figure 3). The two studies used a single-group crossover design in which each patient received four or five applications of SS cream and one of placebo. One study
      • Choi H.K.
      • Xin Z.C.
      • Choi Y.D.
      • et al.
      Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
      used different doses of SS cream; only the results for the maximum dose (0.2 g) are presented. Patients might have had less severe PE than those in some other studies because the inclusion criterion was an IELT shorter than 3 minutes (combined with low partner satisfaction in one study). Adverse effects included a mild burning sensation in 15% of patients (the two studies) and mild pain in 0.04% to 4% of patients (Table 4).
      Figure thumbnail gr3
      Figure 3Intravaginal ejaculatory latency time for secret severance (SS) cream.

       Summary

      The included studies evaluated the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical SS cream in improving IELT and other outcomes. Overall risk of bias was unclear in all studies because of unclear allocation concealment and/or blinding. Studies were clinically heterogeneous and stopwatch-measured IELT was reported in only 5 of 10 studies. Acupuncture increased IELT over placebo (one study; MD = 0.55 minute, P = .001). Ayurvedic herbal medicine increased IELT over placebo (one study; MD = 0.80 minute, P = .001). Topical SS cream improved IELT over placebo in two crossover studies (MD = 8.60 minutes, P < .001), although inclusion criteria were broad (IELT < 3 minutes), and there were mild irritant effects in some patients. SSRIs were more effective on IELT than Chinese herbal medicine (three studies; MD = 1.01 minutes, P = .02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies; MD = 1.92 minutes, P < .00001) or Chinese medicine alone (two studies; MD = 2.52 minutes, P < .00001). Adverse effects were not consistently assessed but where reported were generally mild. There were sparse data on the potential for drug interactions.

      Discussion

      Our systematic review is (to our knowledge) the first to evaluate CAM for PE. All studies were classed as having an overall unclear risk of bias because of limited reporting. Blinding of participants and personnel was difficult in many studies because of the nature of the interventions, although a few studies used placebo. However, because most studies included an active control group (eg, drug treatment), any placebo effect might be expected to occur in the two groups. It was not possible to conduct a formal test for publication bias or produce funnel plots because of the small number of studies in each analysis. However, all but three studies were conducted in single centers,
      • Sun Z.
      • Wang Y.
      • Chen L.
      • et al.
      Clinical study on treatment of premature ejaculation with fluoxetine hydrochloride and tamsulosin.
      • Song G.H.
      • Halmurat U.
      • Geng J.C.
      • et al.
      Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet.
      • Choi H.K.
      • Jung G.W.
      • Moon K.H.
      • et al.
      Clinical study of SS-cream in patients with lifelong premature ejaculation.
      and single-center trials tend to show larger treatment effects than multicenter trials,
      • Dechartres A.
      • Boutron I.
      • Trinquart L.
      • et al.
      Single-center trials show larger treatment effects than multicenter trials: evidence from a meta-epidemiologic study.
      possibly because of a lower likelihood of publication if the result is negative (publication bias), lower methodologic quality, and/or more selected patients.
      Cochrane Collaboration
      Cochrane handbook for systematic reviews of interventions version 5.1.0.
      Regarding outcomes, 9 of 10 included studies assessed IELT but only five reported on stopwatch-measured IELT. Because IELT tends to be positively skewed, it has been suggested that studies should report geometric (rather than arithmetic) mean IELT.
      • Waldinger M.D.
      • Zwinderman A.H.
      • Olivier B.
      • et al.
      Geometric mean IELT and premature ejaculation: appropriate statistics to avoid overestimation of treatment efficacy.
      None of the included studies reported geometric mean IELT, although two studies used the Mann-Whitney U-test for between-group differences because of non-normal distribution of data.
      • Sunay D.
      • Sunay M.
      • Aydogmus Y.
      • et al.
      Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.
      • Xu G.
      • Jiang H.W.
      • Fang J.
      • et al.
      An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.
      Additional outcomes included PEDT, CIPE-5, and IIEF scores. Although it is important that clinical studies assess non-IELT outcomes in addition to IELT,
      • McMahon C.G.
      Ejaculatory latency vs. patient-reported outcomes (PROs) as study end points in premature ejaculation clinical trials.
      there is a need for greater agreement on which measurements are most robust. Duration of the interventions was 2 to 8 weeks in all studies (or one to five applications for SS cream). Only one study (of Chinese medicine) provided follow-up data beyond the end of treatment and reported that differences remained significant 1 month after treatment ended. For most interventions, it was not clear how long the effects might last or whether repeat treatments were effective. This is an issue for all PE treatments.
      An interesting point relates to the nature of CAM therapies. In clinical practice, many CAM therapies involve a holistic approach based on the patient's overall pattern of health. It can be difficult to determine how much of the treatment effect is due to the specific treatment (acupuncture, herbs) and how much is due to the patient-therapist interaction and other aspects (eg, lifestyle advice). Some researchers believe the patient-therapist interaction and other aspects of treatment should be controlled for, whereas others argue that they are a valid element of treatment.
      • Fonnebo V.
      • Grimsgaard S.
      • Walach H.
      • et al.
      Researching complementary and alternative treatments—the gatekeepers are not at home.
      • MacPherson H.
      • Sherman K.
      • Hammerschlag R.
      • et al.
      The clinical evaluation of traditional East Asian systems of medicine.
      • Relton C.
      • O'Cathain A.
      • Thomas K.J.
      ‘Homeopathy’: untangling the debate.
      A related issue is whether CAM therapies are individualized to the patient (eg, in clinical practice, two patients with PE might receive different herbal remedies or acupuncture points depending on their overall symptom picture).
      • Fonnebo V.
      • Grimsgaard S.
      • Walach H.
      • et al.
      Researching complementary and alternative treatments—the gatekeepers are not at home.
      • MacPherson H.
      • Sherman K.
      • Hammerschlag R.
      • et al.
      The clinical evaluation of traditional East Asian systems of medicine.
      All studies included in this review used a standardized treatment across patients within a study (same set of acupuncture points or same Chinese herbal preparation), although treatments varied among studies. Although standardized treatment protocols increase reproducibility, effectiveness of CAM therapies could be compromised by this approach.
      None of the included therapies are commonly provided for PE by Western government health services. This has implications for access and use of these therapies. Acupuncture, Chinese medicine, and Ayurvedic medicine might be available from private practitioners, whereas SS cream currently has limited availability outside Korea. Pragmatically, because there are so many CAM therapies available, it seems unlikely that they will all undergo further evaluation in large-scale studies. Therefore, it might be reasonable to summarize that the CAM therapies reviewed here have some (although limited) evidence for effectiveness in treating PE, and that they might provide another option for patients who favor a mind-body approach or who wish to avoid long-term pharmacologic treatment. It would need to be borne in mind that the effectiveness evidence is not conclusive, and care would need to be taken to monitor for adverse effects and to consider the potential for herb-drug interactions.
      Regarding further research, it would be useful to see further RCTs in a Western setting for any of the included treatments, because all had some (limited) evidence of effectiveness in PE. It would be useful to conduct comparisons against placebo, no treatment, existing therapies (drug or behavioral treatment), and combination treatment. To increase consistency and facilitate meta-analyses, future studies should recruit men meeting the ISSM definition of PE, measure stopwatch-assessed IELT, and report additional outcomes using validated instruments. Additional areas for further study could include optimum duration of therapy and how effects might best be maintained in the long term.

      Conclusions

      There is preliminary evidence for effectiveness of some CAM therapies in PE. However, results are based on clinically heterogeneous, mostly single-center studies of unclear quality. Acupuncture, Ayurvedic medicine, and SS cream improved IELT and other outcomes over placebo based on limited data. Chinese herbal medicine was not as effective as SSRIs, whereas combination treatment with Chinese medicine plus SSRIs improved outcomes over either therapy alone. Adverse effects were not consistently assessed, although where reported they were generally mild, and there were sparse data on the potential for drug interactions. Further well-conducted RCTs of all treatments would be valuable.

      Statement of authorship

        Category 1

      • (a)
        Conception and Design
        • Katy Cooper; Marrissa Martyn-St James; Eva Kaltenthaler; Kath Dickinson; Anna Cantrell
      • (b)
        Acquisition of Data
        • Katy Cooper; Marrissa Martyn-St James; Kath Dickinson; Anna Cantrell
      • (c)
        Analysis and Interpretation of Data
        • Katy Cooper; Marrissa Martyn-St James; Eva Kaltenthaler; Shijie Ren; Kevan Wylie; Leila Frodsham; Catherine Hood

        Category 2

      • (a)
        Drafting the Article
        • Katy Cooper
      • (b)
        Revising It for Intellectual Content
        • Katy Cooper; Marrissa Martyn-St James; Eva Kaltenthaler; Kath Dickinson; Anna Cantrell; Shijie Ren; Kevan Wylie; Leila Frodsham; Catherine Hood

        Category 3

      • (a)
        Final Approval of the Completed Article
        • Katy Cooper; Marrissa Martyn-St James; Eva Kaltenthaler; Kath Dickinson; Anna Cantrell; Shijie Ren; Kevan Wylie; Leila Frodsham; Catherine Hood

      Acknowledgments

      We thank Shijie Ren and Ziyi Lin for translation of articles and Naila Dracup for updating literature searches.

      Appendix 1. Medline search strategy

      • Medline search strategy
        • 1.
          exp Ejaculation/
        • 2.
          exp Premature Ejaculation/
        • 3.
          (premature$ adj3 ejaculat$).ti,ab.
        • 4.
          (early adj3 ejaculat$).ti,ab.
        • 5.
          (rapid adj3 ejaculat$).ti,ab.
        • 6.
          (rapid adj3 climax$).ti,ab.
        • 7.
          (premature$ adj3 climax$).ti,ab.
        • 8.
          (ejaculat$ adj3 pr?ecox).ti,ab.
        • 9.
          or/1-8.
      • Filter 1: Randomized Controlled Trials
        • 10.
          Randomized Controlled Trials as Topic/
        • 11.
          randomized controlled trial/
        • 12.
          Random Allocation/
        • 13.
          Double Blind Method/
        • 14.
          Single Blind Method/
        • 15.
          clinical trial/
        • 16.
          clinical trial, phase i.pt.
        • 17.
          clinical trial, phase ii.pt.
        • 18.
          clinical trial, phase iii.pt.
        • 19.
          clinical trial, phase iv.pt.
        • 20.
          controlled clinical trial.pt.
        • 21.
          randomized controlled trial.pt.
        • 22.
          multicenter study.pt.
        • 23.
          clinical trial.pt.
        • 24.
          exp Clinical Trials as topic/
        • 25.
          or/10-24
        • 26.
          (clinical adj trial$).tw.
        • 27.
          ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw.
        • 28.
          PLACEBOS/
        • 29.
          placebo$.tw.
        • 30.
          randomly allocated.tw.
        • 31.
          (allocated adj2 random$).tw.
        • 32.
          26 or 27 or 28 or 29 or 30 or 31
        • 33.
          25 or 32
        • 34.
          case report.tw.
        • 35.
          letter/
        • 36.
          historical article/
        • 37.
          34 or 35 or 36
        • 38.
          33 not 37
      • Filter 2: Reviews
        • 10.
          review.ab.
        • 11.
          review.pt.
        • 12.
          meta-analysis.ab.
        • 13.
          meta-analysis.pt.
        • 14.
          meta-analysis.ti.
        • 15.
          or/10-14
        • 16.
          letter.pt.
        • 17.
          comment.pt.
        • 18.
          editorial.pt.
        • 19.
          or/16-18
        • 20.
          15 not 19
      • Filter 3: Guidelines
        • 10.
          guideline.pt.
        • 11.
          practice guideline.pt.
        • 12.
          exp Guideline/
        • 13.
          health planning guidelines/
        • 14.
          10 or 11 or 12 or 13

      Supplementary data

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