This paper is in the following e-collection/theme issue:

Scoping Review Protocols (157) Digital Health Reviews (1191)

Published on in Vol 12 (2023)

Preprints (earlier versions) of this paper are available at https://preprints.jmir.org/preprint/41301, first published .
Possible Pathophysiological Roles of Neurotransmitter Systems in Men With Lifelong Premature Ejaculation: Protocol for a Scoping Review

Possible Pathophysiological Roles of Neurotransmitter Systems in Men With Lifelong Premature Ejaculation: Protocol for a Scoping Review

Possible Pathophysiological Roles of Neurotransmitter Systems in Men With Lifelong Premature Ejaculation: Protocol for a Scoping Review

Authors of this article:

Joost Johan Van Raaij1, 2 Author Orcid Image ;   Paddy Koen Camiel Janssen1, 2 Author Orcid Image
Article Authors Cited by (1) Tweetations (2) Metrics

    Protocol

    1Department of Clinical Pharmacy and Toxicology, VieCuri Medical Centre, Venlo, Netherlands

    2Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, Netherlands

    Corresponding Author:

    Paddy Koen Camiel Janssen, PharmD, PhD

    Department of Clinical Pharmacy and Toxicology

    Maastricht University Medical Centre

    P. Debyelaan 25

    Maastricht, 6229 HX

    Netherlands

    Phone: 31 773205186

    Email: paddy.janssen@mumc.nl


    Background: Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders. In the field of LPE, 2 main types of research have been conducted: direct genetic research and pharmacotherapeutic interference of neurotransmitter systems that can relieve the symptoms of LPE in male patients.

    Objective: We aim to provide an overview of studies on neurotransmitter systems as the pathophysiological cause of LPE by investigating direct genetic research or pharmacotherapeutic interference that relieves the main symptom of LPE in male patients.

    Methods: This scoping review will use the PRISMA-ScR tool (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). In addition, this study will use a peer-reviewed search strategy. Systematic searches will be conducted using 5 scientific databases (Cochrane Database of Systematic Reviews, PubMed or MEDLINE, Cumulative Index to Nursing and Allied Health Literature [CINAHL], EMBASE, and Epistemonikos). Additionally, pragmatic searches for relevant information in gray literature databases will be performed. Two reviewers will independently include relevant studies in a 2-stage selection strategy. Finally, data will be extracted from the studies and charted to summarize relevant study characteristics and key findings.

    Results: As of July 2022, we completed the preliminary searches according to the PRESS 2015 guidelines and started to determine the final search terms that we will use in all selected 5 scientific databases.

    Conclusions: This scoping review protocol is the first to focus on neurotransmitter pathways in LPE by combining the results from the genetic and pharmacotherapy studies. The results could help identify potential research gaps or target candidate proteins and neurotransmitter pathways in LPE for further genetic research.

    Trial Registration: Open Science Framework 10.17605/OSF.IO/JUQSD; https://osf.io/juqsd

    International Registered Report Identifier (IRRID): PRR1-10.2196/41301

    JMIR Res Protoc 2023;12:e41301

    doi:10.2196/41301

    Keywords

    drug therapy; genetic research; lifelong premature ejaculation; scoping review 


    Premature ejaculation (PE) is a common sexual problem among men, with a prevalence of 20%-40% when using a broad definition of the term [1-4]. To obtain valuable standardized and reproducible research on PE, a sharp demarcation of the research field and a clear definition of PE are needed. A distinction can be made between the different types of PE. As defined by a panel of experts at an International Society for Sexual Medicine (ISSM) meeting in 2013, the internationally accepted definition of lifelong premature ejaculation (LPE) and acquired premature ejaculation is as follows [5,6]: (1) Ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration (LPE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired premature ejaculation); (2) the inability to delay ejaculation on all or nearly all vaginal penetrations; (3) negative personal consequences, such as distress, bother, frustration, or the avoidance of sexual intimacy.

    LPE is a subtype of PE with a prevalence of <4% in the general population [7]. The other suggested subtypes of PE include variable PE and subjective PE. Since these variants are not part of the genetic LPE, they fall outside the scope of this scoping review.

    In 1943, Schapiro discovered a possible genetic component in the occurrence of LPE in men [8]. Waldinger further elaborated on this result and thus extended the field of genetic research since 1998 [9]. Thereafter, several studies have examined multiple genes and associated them with the occurrence of LPE [10-27]. Although a clear cause of LPE has not yet been revealed, Schapiro [8] reported that patients responded well to sedatives. Other successful treatments for LPE have been described since 1973 and have been further developed in the past 20 years [28-31]. Some drugs, such as dapoxetine, were specifically registered for the treatment of PE [32]. Additionally, neurobiological causes for LPE are supported by the findings that demonstrate that single-psychotherapeutic treatments or sex therapy is not effective for a significant remission of symptoms [5,33-36]. It has been pointed out that neurotransmitter pathways have multiple complex mechanisms, multiple families, and subtypes of receptors, all of which affect one another, making one polymorphism unlikely to be the sole cause of LPE [10,12,37,38]. It is therefore likely that a subset of polymorphisms in one or more neurotransmitter systems may lead to LPE.

    In the field of LPE, 2 main types of research have been conducted. These include genetic research and pharmacological mechanisms that successfully prolong intravaginal ejaculation latency times (IELTs) through pharmacotherapeutic treatment. It is therefore possible to collect evidence on specific neurotransmitter systems. To study neurotransmitter pathways in relation to LPE in this manner, one or more targets can be identified to conduct a targeted strategy for conducting genome-wide association studies (GWAS) and ultimately resolve the cause of LPE.

    A preliminary search for the existing scoping and systematic reviews on this topic was conducted on the January 12, 2022, in the following journals, databases, and search platforms: JBI Evidence Synthesis, Cochrane Database of Systematic Reviews, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PubMed or MEDLINE, Embase, and Epistemonikos. Scoping reviews that combined pharmacological evidence with genetic causes were not available.

    The objective of this scoping review is to provide an overview of studies on neurotransmitter systems as the pathophysiological cause of LPE by investigating direct genetic research or pharmacotherapeutic interference that relieves the main symptom of LPE in male patients.


    Overview

    This scoping review will be conducted from April 2022 in 6 stages using the methodology outlined in Levac et al [39], Peters et al [40], and the JBI Manual for Evidence Synthesis [41]. All sections will be reported in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension for Scoping Reviews) guidelines [42]. Any amendments will be uploaded on the Open Science Framework public page of this study.

    Identifying the Review Questions

    What evidence is currently available that could explain the potentially affected neurotransmitter systems in the pathophysiology of LPE?

    The following evidence can be referred: (1) genetic variation correlated with the occurrence of LPE in affected versus unaffected men or (2) successful neuro-targeted pharmacologic treatment of LPE.

    Identifying Relevant Studies

    Studies will be collected from the Cochrane Database of Systematic Reviews, PubMed or MEDLINE, CINAHL, Embase, and Epistemonikos databases. Additionally, references of studies will be checked for relevancy and, if eligible, added to this scoping review (snowballing). The reference list of reviews found through the electronic search will be checked to ensure that relevant articles are included in the scoping review. Finally, we will perform pragmatic searches in gray literature databases for relevant information. These include the Grey Literature Report, OpenGrey, Web of Science Conference Proceedings, and local, national, and international organization websites. For inclusion websites should comply with the eEurope 2002 quality criteria [43].

    A publication timeline or language restriction will not be set. A systemic search term will be developed using keywords and MeSH terms with the Boolean operators “AND/OR.” Search terms will be applied to the titles and abstracts of the relevant studies. An example of the initial search terms is included in Multimedia Appendix 1. The generated search terms will be peer-reviewed according to the Peer Review of Electronic Search Strategies 2015 guidelines [44]. Google translate will be used as a supportive tool for screening and including non-English studies [45]. Eventually, all included studies will be imported into the Mendeley research software. Studies collected from different sources will be deduplicated in EndNote [46].

    Study Selection

    Study selection will occur in 2 stages. The first inclusion will be based on eligibility by screening the title and abstract. Articles that are classified as relevant will be included for full-text review and for final inclusion in the scoping review. The Rayyan software tool will be used for the blind systematic inclusion and exclusion of studies [47]. Studies will be independently selected by 2 individual reviewers. Reviewers will meet when approximately 10%, 50%, and 90% of the studies have been screened to discuss dissent regarding study selection. A PRISMA-ScR flow diagram will be used to describe the study selection process. The diagram will be added to the publication of this scoping review.

    All inclusion and exclusion criteria are displayed in Table 1.

    Table 1. Search strategy using inclusion and exclusion criteria based on the patient population, intervention, comparison, outcomes, and study designs.
    ParameterInclusion criteriaExclusion criteria
    PatientAdult males with LPEa (aged ≥18 years)Populations not matching with one of the following definitions: ISSMb 2007, ISSM 2013, DSM-5c, or Definition 1d



    InterventionGenotyping or pharmacotherapy treatmentPharmacotherapy studies using a topical anesthetic or locally active agents or with traditional or herbal medicine
    ComparisonMales without LPE in genotype studies or drug naïve or washed-out patients with LPE in pharmacotherapy studiesN/Ae
    OutcomeComparison of genotype or gene’s or x-fold increase in sIELTsf by drug treatmentN/A
    Study designIn pharmacotherapy studies: RCTsg, cross-over drug studies, single-arm trials with a baseline sIELT, or case reports with a baseline sIELTN/A

    aLPE: lifelong premature ejaculation.

    bISSM: International Society for Sexual Medicine.

    cDSM-5: Diagnostic and Statistical Manual of Mental Disorders.

    dDefinition 1: studies using a cut-off IELT of approximately 1.5 minutes after vaginal penetration, measured using the stopwatch method. Symptoms must be present from the first sexual encounter to all sexual partners.

    eN/A: not applicable.

    fsIELTs: stopwatch-measured intravaginal ejaculation latency time.

    gRCT: randomized controlled trial.

    Inclusion Criteria

    Patient Population

    Studies qualify for inclusion if the patient population meets the criteria for LPE, as stated in the ISSM 2007-2013 definition or in the 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [5,7,48]. IELTs must be measured using the stopwatch method that is the standardized outcome method demanded in drug registration by the European Medicine Association [49]. As these criteria were defined in 2007, the studies performed before this time have a risk of diagnosing patients with LPE with vague terminology or less reliable parameters such as self-reported estimated ejaculatory latency times (eIELTs) using questionnaires [30,50,51]. However, by rejecting the studies executed before 2007, we may overlook useful data; we have therefore designed a secondary inclusion term for the studies performed before 2007. These terms approach the ISSM 2007 or DSM-5 definition as closely as possible. The prior and post-2007 definitions used in the DSM-III [52], DSM IV [53], DSM-IV-TR [54], ICD-9 [55], ICD-10 [56,57], and ICD-11 [58] or the definition used by the American Urological Association Guideline on the pharmacologic management of PE [59] have been found to be inferior to correctly diagnosed LPE [1,60].

    Studies before 2007 are eligible if they use a cutoff of approximately 1.5 minutes after vaginal penetration, measured using the stopwatch method. Symptoms must be present from the first sexual encounter to all sexual partners. This additional definition is based on the proposals for definitions published by Waldinger et al in 2006 [1].

    Pharmacotherapy Studies

    We will include the pharmacotherapy studies that meet the following criteria: (1) randomized placebo-controlled trials; (2) cross-over designs; (3) single-arm trials with a baseline stopwatch measuring intravaginal ejaculation latency time (sIELT); and (4) case reports with a baseline sIELT.

    Exclusion Criteria

    The exclusion criteria here are pharmacotherapy studies using traditional or herbal medicines and local topical anesthetic agents, as these drugs do not interfere with the central neurotransmission systems.

    Charting the Data

    Data will be collected by the research team with research software that is yet to be specified. Data will be collected as an iterative process, in which reviewers extract and update data continuously. Data will be collected as shown in Figure 1. To test whether the framework matches the research question and aim of the study, 2 reviewers will independently use the data charting form using the data extracted from the first 5 articles.

    If any data are unclear or incomplete, the corresponding authors will be contacted for additional details on the performed studies. If additional information will not be obtained, a comment on this issue will be placed in the charting table.

    ‎
    Figure 1. Example of data charting form. LPE: lifelong premature ejaculation; sIELTs: stopwatch-measured intravaginal ejaculation latency time; Tx: drug therapy; wk: week(s).

    Collating, Summarizing, and Reporting the Results

    The key findings of the included studies will be summarized. A distinction will be made between genotype research studies and pharmacotherapeutic drug studies, ordered by the targeted neurotransmission protein subtype. Quantitative data will include, for example, a factor-fold increase in sIELTs by pharmacotherapy or a correlation with specific gene types. This will provide an overview of evidence in the field and could help identify potential research gaps or target protein and neurotransmitter pathways for further genetic research.


    As of July 2022, we completed the preliminary searches according to the PRESS 2015 guidelines and started to determine the final search terms that we will use in all selected 5 scientific databases.


    This scoping review protocol is the first to focus on neurotransmitter pathways in LPE by combining the results from the genetic and pharmacotherapy studies. The results could help to identify potential research gaps or target candidate proteins and neurotransmitter pathways in LPE for further genetic research. This could ultimately lead to an improvement in therapy for patients with LPE.

    In this scoping review a sharp demarcated definition of LPE will be used to prevent inclusion of non-LPE males by overdiagnosis. Furthermore, the method of this scoping review complies with the most recent guidelines using the PRISMA-ScR tool. In addition, this study will use a peer-reviewed search strategy without language restrictions; therefore, a robust and systematic foundation for thorough scientific research is laid. The final scoping review will be published in a peer-reviewed journal and information will be disseminated in scientific meetings.

    This scoping review is limited to wide evidence collection; the quality of evidence of studies will only be partly evaluated since it is not a standard element of scoping review methods. In LPE research the quality of studies is widely discussed [51,61-63]. Confounded published studies are not excluded in advance because this scoping review focusses mainly on wide evidence collection as input for a targeted strategy in a GWAS. To assess potential confounders or outcome differences by ethnicity, patient characteristics and social information of studies will be charted and discussed.

    To date several reviews on LPE have been conducted. However, this will be the first scoping review focusing on neurotransmitter pathways in LPE by combining the results from the genetic and pharmacotherapy studies. With this protocol a scoping review could be conducted systemically leading to further input for future candidate gene studies or GWAS and ultimately improve LPE care.

    Acknowledgments

    The authors thank Frits van Osch, a research assistant, who provided critical feedback and helped shape this research. This study was funded by the Prof Dr Marcel Waldinger Foundation, The Netherlands. The funding body had no influence or participation in shaping the research protocol.

    Authors' Contributions

    PKCJ is the guarantor. JJVR took the lead in writing and shaping the protocol. PKCJ provided feedback.

    Conflicts of Interest

    None declared.

    ‎
    Multimedia Appendix 1

    Preliminary search terms.

    DOCX File , 14 KB
    1. Waldinger MD, Schweitzer DH. Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part II--proposals for DSM-V and ICD-11. J Sex Med 2006;3(4):693-705. [CrossRef] [Medline]
    2. Frank E, Anderson C, Rubinstein D. Frequency of sexual dysfunction in "normal" couples. N Engl J Med 1978;299(3):111-115. [CrossRef] [Medline]
    3. Nettelbladt P, Uddenberg N. Sexual dysfunction and sexual satisfaction in 58 married Swedish men. J Psychosom Res 1979;23(2):141-147. [CrossRef] [Medline]
    4. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281(6):537-544. [CrossRef] [Medline]
    5. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Adaikan PG, et al. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med 2014;2(2):60-90 [FREE Full text] [CrossRef] [Medline]
    6. Serefoglu EC, McMahon CG, Waldinger MD, Althof SE, Shindel A, Adaikan G, 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. J Sex Med 2014;11(6):1423-1441 [FREE Full text] [CrossRef] [Medline]
    7. McMahon CG, Althof S, Waldinger MD, Porst H, Dean J, Sharlip I, International Society for Sexual Medicine Ad Hoc Committee for Definition of Premature Ejaculation. An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine Ad Hoc Committee for the definition of premature ejaculation. BJU Int 2008;102(3):338-350. [CrossRef] [Medline]
    8. Schapiro B. Premature ejaculation: a review of 1130 cases. J Urol 1943;50(3):374-379. [CrossRef]
    9. Waldinger MD, Rietschel M, Nöthen MM, Hengeveld MW, Olivier B. Familial occurrence of primary premature ejaculation. Psychiatr Genet 1998;8(1):37-40. [CrossRef] [Medline]
    10. Wang F, Luo D, Chen J, Pan C, Wang Z, Fu H, et al. Genome-wide association analysis to search for new loci associated with lifelong premature ejaculation risk in Chinese male han population. World J Mens Health 2022;40(2):330-339 [FREE Full text] [CrossRef] [Medline]
    11. Janssen PKC, Bakker SC, Réthelyi J, Zwinderman AH, Touw DJ, Olivier B, et al. Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation. J Sex Med 2009;6(1):276-284. [CrossRef] [Medline]
    12. Janssen PKC, van Schaik R, Zwinderman AH, Olivier B, Waldinger MD. The 5-HT1A receptor C(1019)G polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation. Pharmacol Biochem Behav 2014;121:184-188. [CrossRef] [Medline]
    13. Janssen PK, von Schaik R, Olivier B, Waldinger MD. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation. Asian J Androl 2014;16(4):607-610 [FREE Full text] [CrossRef] [Medline]
    14. Janssen PK, Touw D, Schweitzer DH, Waldinger MD. Nonresponders to daily paroxetine and another SSRI in men with lifelong premature ejaculation: a pharmacokinetic dose-escalation study for a rare phenomenon. Korean J Urol 2014;55(9):599-607 [FREE Full text] [CrossRef] [Medline]
    15. Ozbek E, Tasci AI, Tugcu V, Ilbey YO, Simsek A, Ozcan L, et al. Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population. Asian J Androl 2009;11(3):351-355 [FREE Full text] [CrossRef] [Medline]
    16. Safarinejad MR. Polymorphisms of the serotonin transporter gene and their relation to premature ejaculation in individuals from Iran. J Urol 2009;181(6):2656-2661. [CrossRef] [Medline]
    17. Jern P, Westberg L, Johansson A, Gunst A, Eriksson E, Sandnabba K, et al. A study of possible associations between single nucleotide polymorphisms in the serotonin receptor 1A, 1B, and 2C genes and self-reported ejaculation latency time. J Sex Med 2012;9(3):866-872. [CrossRef] [Medline]
    18. Ozbek E, Otunctemur A, Simsek A, Polat EC, Ozcan L, Köse O, et al. Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation. Clinics (Sao Paulo) 2014;69(11):710-713 [FREE Full text] [CrossRef] [Medline]
    19. Huang Y, Zhang X, Gao J, Tang D, Gao P, Peng D, et al. Association of STin2 VNTR polymorphism of serotonin transporter gene with lifelong premature ejaculation: a case-control study in Han Chinese subjects. Med Sci Monit 2016;22:3588-3594 [FREE Full text] [CrossRef] [Medline]
    20. Luo S, Lu Y, Wang F, Xie Z, Huang X, Dong Q, et al. Association between polymorphisms in the serotonin 2C receptor gene and premature ejaculation in Han Chinese subjects. Urol Int 2010;85(2):204-208. [CrossRef] [Medline]
    21. Roaiah MF, Elkhayat YI, Rashed LA, GamalEl Din SF, El Guindi AM, Abd El Salam MA. Study of the prevalence of 5 HT-2C receptor gene polymorphisms in Egyptian patients with lifelong premature ejaculation. Andrologia 2018;50(2):e12855. [CrossRef] [Medline]
    22. Roaiah MF, Elkhayat YI, Rashed LA, GamalEl Din SF, El Guindi AM, Soliman IF, et al. 5HT-1A receptor polymorphism effects ejaculatory function in Egyptian patients with lifelong premature ejaculation. Rev Int Androl 2019;17(4):138-142. [CrossRef] [Medline]
    23. Safarinejad MR. Relationship between premature ejaculation and genetic polymorphisms of the dopamine transporter gene (SLC6A3). BJU Int 2011;108(2):292-296. [CrossRef] [Medline]
    24. Santtila P, Jern P, Westberg L, Walum H, Pedersen CT, Eriksson E, et al. The dopamine transporter gene (DAT1) polymorphism is associated with premature ejaculation. J Sex Med 2010;7(4 Pt 1):1538-1546. [CrossRef] [Medline]
    25. Eltonsi TK, Tawfik TM, Rashed LA, GamalEl Din SF, Mahmoud MA. Study of the link between dopamine transporter gene polymorphisms and response to paroxetin and escitalopram in patients with lifelong premature ejaculation. Int J Impot Res 2017;29(6):235-239. [CrossRef] [Medline]
    26. Jern P, Johansson A, Strohmaier J, Treutlein J, Piha J, Rietschel M. Preliminary evidence for an association between variants of the catechol-O-methyltransferase (COMT) gene and premature ejaculation. J Sex Med 2017;14(12):1558-1565. [CrossRef] [Medline]
    27. Khan HL, Bhatti S, Abbas S, Khan YL, Gonzalez RMM, Aslamkhan M, et al. Serotonin transporter (5-HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation. Andrology 2018;6(6):916-926 [FREE Full text] [CrossRef] [Medline]
    28. Eaton H. Clomipramine in the treatment of premature ejaculation. J Int Med Res 1973;1(5):432-434. [CrossRef]
    29. Castiglione F, Albersen M, Hedlund P, Gratzke C, Salonia A, Giuliano F. Current pharmacological management of premature ejaculation: a systematic review and meta-analysis. Eur Urol 2016;69(5):904-916. [CrossRef] [Medline]
    30. Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. Int J Impot Res 2004;16(4):369-381. [CrossRef] [Medline]
    31. Jian Z, Wei X, Ye D, Li H, Wang K. Pharmacotherapy of premature ejaculation: a systematic review and network meta-analysis. Int Urol Nephrol 2018;50(11):1939-1948. [CrossRef] [Medline]
    32. Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJG, Shabsigh R, Dapoxetine Study Group. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006;368(9539):929-937. [CrossRef] [Medline]
    33. Althof SE. Psychosexual therapy for premature ejaculation. Transl Androl Urol 2016;5(4):475-481. [CrossRef]
    34. Melnik T, Althof S, Atallah AN, Puga ME, Glina S, Riera R. Psychosocial interventions for premature ejaculation. Cochrane Database Syst Rev 2011(8):CD008195 [FREE Full text] [CrossRef] [Medline]
    35. Cooper K, Martyn-St James M, Kaltenthaler E, Dickinson K, Cantrell A, Wylie K, et al. Behavioral therapies for management of premature ejaculation: a systematic review. Sex Med 2015;3(3):174-188 [FREE Full text] [CrossRef] [Medline]
    36. Frühauf S, Gerger H, Schmidt HM, Munder T, Barth J. Efficacy of psychological interventions for sexual dysfunction: a systematic review and meta-analysis. Arch Sex Behav 2013;42(6):915-933 [FREE Full text] [CrossRef] [Medline]
    37. van Raaij JJ, Hua KH, de Vries F, Janssen PKC. His452Tyr 5-HT2A polymorphism and intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation. Int J Impot Res 2021 Nov 17. [CrossRef] [Medline]
    38. Mostafa T, Abdel-Hamid IA, Taymour M, Ali OI. Gene variants in premature ejaculation: systematic review and future directions. Sex Med Rev 2020;8(4):586-602. [CrossRef] [Medline]
    39. Levac D, Colquhoun H, O'Brien KK. Scoping studies: advancing the methodology. Implement Sci 2010;5:69 [FREE Full text] [CrossRef] [Medline]
    40. Peters MDJ, Godfrey CM, Khalil H, McInerney P, Parker D, Soares CB. Guidance for conducting systematic scoping reviews. Int J Evid Based Healthc 2015;13(3):141-146. [CrossRef] [Medline]
    41. Aromataris E, Munn Z. JBI manual for evidence synthesis. JBI. 2020.   URL: https://jbi-global-wiki.refined.site/space/MANUAL [accessed 2022-02-17]
    42. Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 2018;169(7):467-473 [FREE Full text] [CrossRef] [Medline]
    43. Commission of the European Communities‚ Brussels. eEurope 2002: quality criteria for health related websites. J Med Internet Res 2002;4(3):E15 [FREE Full text] [CrossRef] [Medline]
    44. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS peer review of electronic search strategies: 2015 guideline statement. J Clin Epidemiol 2016;75:40-46 [FREE Full text] [CrossRef] [Medline]
    45. Jackson JL, Kuriyama A, Anton A, Choi A, Fournier JP, Geier AK, et al. The accuracy of google translate for abstracting data from non-English-language trials for systematic reviews. Ann Intern Med 2019;171(9):677-679. [CrossRef] [Medline]
    46. Bramer WM, Giustini D, de Jonge GB, Holland L, Bekhuis T. De-duplication of database search results for systematic reviews in EndNote. J Med Libr Assoc 2016;104(3):240-243. [CrossRef] [Medline]
    47. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev 2016;5(1):210 [FREE Full text] [CrossRef] [Medline]
    48. American Psychiatric Association. Diagnostics and Statistics Manual of Mental Disorders. DSM-V. 5th ed. Washington, DC: American Psychiatric Association Publishing; 2014.
    49. Waldinger MD, Schweitzer DH. Method and design of drug treatment research of subjective premature ejaculation in men differs from that of lifelong premature ejaculation in males: proposal for a new objective measure (part 1). Int J Impot Res 2019;31(5):328-333. [CrossRef] [Medline]
    50. Waldinger MD, Schweitzer DH. Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part I--validity of DSM-IV-TR. J Sex Med 2006;3(4):682-692. [CrossRef] [Medline]
    51. Waldinger MD. The dangers that threaten current research of premature ejaculation: using validated questionnaires, performing conjuring tricks with statistics, and refusing to use real-time stopwatch measurements of intravaginal ejaculation latency time. Eur Urol Focus 2017;3(2-3):246-247. [CrossRef] [Medline]
    52. American Psychiatric Association. Diagnostics and Statistics Manual of Mental Disorders: DSM-III. 3rd ed. Washington DC: American Psychiatric Association; 1980.
    53. American Psychiatric Association. Diagnostics and Statistics Manual of Mental Disorders: DSM-IV. 4th ed. Washington DC: American Psychiatric Association; 1994.
    54. American Psychiatric Association. Diagnostics and Statistics Manual of Mental Disorders: DSM-IV TR. 4th ed. Washington DC: American Psychiatric Association; 2000.
    55. World Health Organisation. International Classification of Diseases (ICD-9-CM). Manual of the International Statistical Classification of Diseases, 9th Revision, Clinical Modification. 9th ed. Geneva: World Health Organization; 1978.
    56. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization; 1992.
    57. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. 9th ed. Geneva: World Health Organization; 1993.
    58. ICD-11 for mortality and morbidity statistics. 2019.   URL: https://icd.who.int/browse11/l-m/en [accessed 2022-02-04]
    59. Montague DK, Jarow J, Broderick GA, Dmochowski RR, Heaton JPW, Lue TF, AUA Erectile Dysfunction Guideline Update Panel. AUA guideline on the pharmacologic management of premature ejaculation. J Urol 2004;172(1):290-294. [CrossRef] [Medline]
    60. Waldinger MD, Schweitzer DH. Differences between ICD-11 MMS and DSM-5 definition of premature ejaculation: a continuation of historical inadequacies and a source of serious misinterpretation by some European regulatory agencies (PART 2). Int J Impot Res 2019;31(5):310-318. [CrossRef] [Medline]
    61. Ventus D, Ristilä M, Gunst A, Kärnä A, Arver S, Piha J, et al. Reply from authors re: Marcel D. Waldinger. The dangers that threaten current research of premature ejaculation: using validated questionnaires, performing conjuring tricks with statistics, and refusing to use real-time stopwatch measurements of intravaginal ejaculation latency time. Eur Urol Focus 2017;3(4-5):510-513. [CrossRef] [Medline]
    62. Janssen PK, Olivier B, Zwinderman AH, Waldinger MD. Measurement errors in polymerase chain reaction are a confounding factor for a correct interpretation of 5-HTTLPR polymorphism effects on lifelong premature ejaculation: a critical analysis of a previously published meta-analysis of six studies. PLoS One 2014;9(3):e88031 [FREE Full text] [CrossRef] [Medline]
    63. Waldinger MD, Janssen PK, Schweitzer DH. Re: Polymorphisms of the serotonin transporter gene and their relation to premature ejaculation in individuals from Iran. J Urol 2009;182(6):2983. [CrossRef] [Medline]

    ‎
    CINAHL: cumulative Index to Nursing & Allied Health Literature DSM-5: Diagnostic and Statistical Manual of Mental Disorders
    GWAS: genome-wide association study
    IELT: intravaginal ejaculatory latency time
    ISSM: International Society of Sexual Medicine
    LPE: lifelong premature ejaculation
    PE: premature ejaculation
    PRISMA-ScR: Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension for Scoping Reviews

    Edited by A Mavragani; submitted 21.07.22; peer-reviewed by V Gadicherla, R Segraves, I Iqbal; comments to author 24.01.23; revised version received 08.02.23; accepted 08.02.23; published 13.03.23

    Copyright

    ©Joost Johan Van Raaij, Paddy Koen Camiel Janssen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.03.2023.

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.