【医脉通】2020+SIAMS临床指南：早泄的管理.pdf

Vol.:(0123456789)1 3Journal of Endocrinological Investigation https:/doi.org/10.1007/s40618-020-01458-4CONSENSUS STATEMENTManagement ofpremature ejaculation:aclinical guideline fromtheItalian Society ofAndrology andSexual Medicine(SIAMS)A.Sansone1 A.Aversa2 G.Corona3 A.D.Fisher4 A.M.Isidori5 S.LaVignera6 E.Limoncin1 M.Maggi7 M.Merico8 E.A.Jannini1 Received:3 October 2020/Accepted:20 October 2020 Italian Society of Endocrinology(SIE)2020AbstractPremature ejaculation(PE)is the most prevalent male sexual dysfunction,and the most recently defined.PE is often mistak-enly considered a purely psychosexological symptom by patients:the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients side,making PE the most underdiagnosed sexual complaint.However,an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE.In the present document by the Italian Society of Andrology and Sexual Medicine(SIAMS),we propose 33 recommendations concerning the definition,pathophysiol-ogy,treatment and management of PE aimed to improve patient care.These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions,such as prostate inflammation,endocrine disorders,and other sexual dysfunctions,and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach.New therapeutic options,as well as combination and off-label treatments,are also described.IntroductionThe inclusion of premature ejaculation(PE)in the radar of science and medicine is relatively recent and still debated:the perception that PE is a psychological or,at the best,sexological symptom,almost exclusively due to behavioral-relational derangements is indeed well-rooted 13.Patients and media are only partially aware of the solid body of evi-dence produced in the context of diagnosis,pathogenesis and treatment of PE.Being one of the“youngest”topics for sexual medicine,many aspects of PE still need to be clarified on the basis of adequate evidence.The aim of this clinical guideline is to examine the current findings able to impact on the clinical management of the patient and the couple with PE.MethodsThe Italian Society of Andrology and Sexual Medicine(SIAMS),one of the leading national scientific societies in the related fields,commissioned an expert task force to pro-vide an updated guideline on PE.Following scrutiny and discussion of the best evidence from published literature *E.A.Jannini 1 Chair ofEndocrinology andMedical Sexology(ENDOSEX),Department ofSystems Medicine,University ofRome Tor Vergata,via Montpellier 1,00133Rome,Italy2 Department ofExperimental andClinical Medicine,University ofCatanzaro Magna Graecia,Catanzaro,Italy3 Endocrinology Unit,Medical Department,Azienda-Usl,Maggiore-Bellaria Hospital,Bologna,Italy4 Andrology,Womens Endocrinology andGender Incongruence Unit,Florence University Hospital,Florence,Italy5 Department ofExperimental Medicine,Sapienza University ofRome,Rome,Italy6 Department ofClinical andExperimental Medicine,University ofCatania,Catania,Italy7 Endocrinology Unit,Department ofExperimental,Clinical andBiomedical Sciences,University ofFlorence,Florence,Italy8 Department ofMedicine,Operative Unit ofAndrology andMedicine ofHuman Reproduction,University ofPadova,Padua,Italy Journal of Endocrinological Investigation1 3available in PubMed,the authors generated a series of con-sensus recommendations according to the Grading of Rec-ommendations,Assessment,Development,and Evaluation(GRADE)system 4.The strength of recommendations and the quality of the evidence are expressed in four levels:denotes“very low-quality evidence”,“low quality”,“moderate quality”and “high quality”.In addition,the number 1 denotes a strong rec-ommendation and is expressed with the phrase we recom-mend,whereas the number 2 denotes a weaker recom-mendation and it is expressed with the phrase we suggest.The strength also reflects the confidence that authors have that patients and couples with PE who receive recommended care will be better off.According to SIAMS rulings,these Guidelines have been prepared by a team of experts on the topic coordinated by the senior author and two members of the Guideline Com-mittee of the Society,then sent to the SIAMS Executive Committee and to the Directors of all SIAMS Excellence Centres for revisions and/or approval.Guidelines have then been announced by mail and published for two weeks on the Societys website,siams.info,so that all SIAMS Mem-bers could provide further comments and suggest additional minor revisions.Following this last step,the present manu-script has been submitted to the Journal of Endocrinological Investigation for the normal process of international peer reviewing.Definitions ofpremature ejaculationRecommendation#1.We recommend using the Interna-tional Society of Sexual Medicine(ISSM)PE definitions for experimental and scientific purposes(1).Recommendation#2.We suggest to define PE,for clini-cal purposes,as:(i)a persistent and recurrent subjective perception of loss of control over the mechanism of ejacu-lation in presence of proper erotic stimuli;(ii)a subjective,PE-related,distress induced in the patient and in the partner;(iii)a short intravaginal ejaculatory latency time(IELT),from penetration to ejaculation,subjectively perceived and partner-perceived IELT,(PIELT,and PPIELT,respectively)or objectively(stopwatch IELT,SIELT)measured as being lower than 180s.(1).Note that the order(i),(ii),and(iii)here mentioned reflect the clinical importance of each aspect of the tridimensional definition of PE.Recommendation#3.We suggest that,in the real-life clinical practice,the same definition could be applied to other sexual stimuli,such as masturbation(MELT),or oral(OELT)and anal(AELT)intercourses,as well to non-het-erosexual settings 5(2).Recommendation#4.We suggest recording the Patients Reported Outcomes(PROs),as resulting from psychometric tests,and when possible,SIELT,PIELT,PPIELT,MELT,OELT,and AELT both during diagnosis and therapeutic follow-up(2).EvidenceThe current most widely used definitions are from the Inter-national Society of Sexual Medicine(ISSM 6),from the Diagnostic and Statistical Manual of Mental Disorders,in its fifth revision(DSM-5 7),and,more recently,from the 11th Revision of the International classification of diseases for mortality and morbidity statistics(ICD-11)8.Table1 summarize the similarities and differences among the three definitions.In 2013,DSM defined PE as“a male sexual dysfunction characterized by a persistent or recurrent pattern of ejacu-lation occurring during partnered sexual activity within approximately 1min following vaginal penetration and before the individual wishes it.The symptoms must have been present for at least 6months and experienced on almost all(75100%)occasions of sexual activity(situational or generalized contexts).The symptoms cause clinically sig-nificant distress in the individual and the sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress and not attribut-able to substance/medication or another medical condition”7.More recently,the ISSM defined PE as a“male sexual dysfunction characterized by ejaculation that always or nearly always occurs prior to or within about 1min of vagi-nal penetration from the first sexual experience(lifelong premature ejaculation),OR a clinically significant reduc-tion in latency time,often to about 3min or less(acquired premature ejaculation);the inability to delay ejaculation on all or nearly all vaginal penetrations;and negative personal consequences,such as distress,bother,frustration,and/or the avoidance of sexual intimacy”6.Finally,in 2018,the ICD11 8 defines male early ejacu-lation as characterized by ejaculation that occurs prior to or within a very short duration of the initiation of vaginal penetration or other relevant sexual stimulation,with no or little perceived control over ejaculation.The pattern of early ejaculation occurs episodically or persistently over a period of at least several months and is associated with clinically significant distress.The ICD-11 identifies five categories:(1)lifelong,generalized;(2)lifelong,situational;(3)acquired,generalized;(4)acquired,situational;(5)unspecified(as a residual category).In respect to cut-offs,the past definitions of PE(including the ICD-10)accounted for the category of severe objective PE,when occurring before penetration Journal of Endocrinological Investigation 1 3or with an IELT 15s(as opposed to moderate,with an IELT 1min;or mild,with an IELT 2min).Then,the ISSM,based on epidemiological studies set up a different criterion of 75%Always or nearly alwaysEpisodically or persistentlyIELT1min1min for generalized3min for acquiredAssociated distressControlEjaculation before the individual wishes itInability to delay ejaculationNo or little perceived con-trol over ejaculationTriggerVaginal penetrationVaginal penetrationVaginal penetration or other relevant sexual stimulationExclusion criteriaNot better explained by a nonsexual mental disorder Journal of Endocrinological Investigation1 3RemarksWhile no study has proven(nor attempted to investigate)an increase in type-5 phosphodiesterase(PDE5)expres-sion in patients with erectile dysfunction,the hypothesis that selected forms of PE,such as LPE,may be related to a genetic pathogenesis has often been reported in literature,but with limited evidence in support 15,16.This was also due to the apodictic perception that a lifelong symptom should have a genetic nature,as well to the exclusive initial interest in LPE,which appeared as the only or at least the most epidemiologically frequent form of PE.HyperthyroidismRecommendation#6.We suggest thyroid-stimulating hor-mone(TSH)evaluation in all subjects with APE with symp-toms of possible thyroid hyperfunction(2).Recommendation#7.We suggest treating underlying clinical or subclinical hyperthyroidism to improve PE before any symptomatic treatment(2).EvidenceTable2 summarizes the available studies investigating the association between HT and APE.Two types of stud-ies have been performed:(i)investigating the prevalence of HT in subjects with PE 1720 and(ii)investigating the prevalence of PE in subjects with HT 21,22.The prevalence of HT in PE subjects ranged from 2.2 to 15%.In two 17,19 out of three studies 20,where a control population was investigated,HT was more prevalent in PE subjects than in control 17,19,20.Note that the experi-mental setting of Waldinger etal.2005 20 was limited to the surprising number of 600 patients with LPE(no APE)and note that lifelong HT is virtually not existing.Two studies 21,22 investigated the effect of treat-ing HT on IELT and found that treatment even in sub-clinical formsalmost doubles ejaculatory time,therefore strengthening the hypothesis that HT could have a causa-tive role in the pathogenesis of PE.RemarksIt is important to recognize that available evidence is only derived from observational studies and open label inter-ventional trial,as no Randomized Clinical Trial(RCT)is currently available.In addition,although HT can be asso-ciated with APE,the prevalence of HT in overall PE popu-lation is quite modest.Hence,TSH measurement should be indicated in the presence of specific symptoms or signs or in patients with acquired forms of PE.Table 2 Studies investigating the association between hyperthyroidism and premature ejaculationPE premature ejaculation,IELT Intravaginal ejaculatory latency timeSourceType of patient popu-lationNumber/mean age(years)patient popu-lationPrevalence of hyperthyroid-ism in patient population number(%)Mean IELT(sec)before hyperthyroid-ism treatmentMean IELT(sec)after hyperthyroid-ism treatmentType of con-trol popula-tionNumber/mean age(years)control popu-lationPrevalence of hyperthyroid-ism in control population number(%)Waldinger etal.2005 20Lifelong PENR14/620(2.2)NRNRGeneral Dutch populationNR16/620(2.5%)Carani etal.2005 21Men with hyperthy-roidism34/43.234/34(100)124 30240 30NRNRNRCihan etal.2009 22Men with hyperthy-roidism43/48.043/43(100)75.8 99.3123.2 96.4NRNRNROzturk etal.2012 19Outpatients with PE107/45.114/107(8.4)NRNRHealthy men94/48.14/94(4.25)Corona etal.2012 17Outpatients with PE855/51.3Lifelong PE 17/322(5.3%)Acquired PE 13/530(2.5%)NRNREMAS study florentine sample433/60.13/433(0.5%)Culha etal.2019 18Outpatients with PE53/42.418/53(15.09)27.25 22.34NRNRNRNR Journal of Endocrinological Investigation 1 3Prostatitis/chronic pelvic pain syndromeRecommendation#8.We suggest excluding chronic prosta-titis/chronic pelvic pain syndrome in all subjects complain-ing of PE(2).Recommendation#9.We suggest a trial with specific antibiotic in patients with PE associated with bacterial pros-tatitis before any symptomatic treatment of PE(2).EvidenceDespite the well-known pivotal role of prostate in the mechanism of ejaculation,the individuation of subacute/paucisymptomatic/chronic prostatic inflammations and infections as a possible risk factor of PE was character-ized by an initial skepticism from the urological commu-nity.Prevalence of PE has been esteemed up to the 77%in patients with male accessory gland inflammation(MAGI)2326,being higher in those positive for ultrasound signs 27,28.A recent meta-analysis investigated the prevalence of PE in subjects with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)29.Thirteen observational studies involving 6819 subjects were scrutinized.Pooled effect size was 0.40(95%CI 0.30.5,I2=989%,p 0.001)suggesting a 40%increase in the risk of having PE in subjects with CP/CPPS.However,studies included in the meta-analysis were often not excellent in quality,relying on different definitions and instruments for investigating both CP/CPPS and PE.Subjects with PE often show symptoms and signs compat-ible with CP/CPPS,as confirmed by many different studies 18,25,26.A lower number of studies investigated the effect of treat-ing CP/CPPS on IELT in PE subjects 3032.This was most probably due to the heterogenic nature of CP/CPPS that is supported by a demonstrable infection only in a minority of cases.Interestingly,in such cases,antibiotic treatment improved IELT and other PE parameters 3032.RemarksThe available evidence was derived mainly from observa-tional studies with obvious methodological limitations,as previously stated.Hence,due to the observational nature of the data,no final causal inference can be drawn.Although the effect of antibiotic treatment on IELT suggests that pros-tatitis is an organic risk factor for PE,the cohorts investi-gated were frequently small and interventions were neither randomized nor controlled.However,no other organic risk factor for PE has been studied more consistently,extensively