Attitudes and perceptions towards vulvar and vaginal atrophy in Italian post-menopausal women: Evidence from the European REVIVE survey

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ContentslistsavailableatScienceDirect

Maturitas

j o ur na l h o me pa g e :w w w . e l s e v i e r . c o m / l o c a t e / m a t u r i t a s

Attitudes

and

perceptions

towards

vulvar

and

vaginal

atrophy

in

Italian

post-menopausal

women:

Evidence

from

the

European

REVIVE

survey

Rossella

E. Nappi

a,∗

_,

_Martire

_Particco

b

_,

_Nicoletta

_Biglia

c

_,

_Angelo

_Cagnacci

d

_,

Costantino

Di

Carlo

e

_,

_Stefano

_Luisi

f

_,

_Anna

_Maria

_Paoletti

g

a_Research_Center_for_Reproductive_Medicine,_{Gynecological}_{Endocrinology}_and_Menopause,_IRCCS_S._Matteo_Foundation,_Department_of_Clinical,_Surgical,

DiagnosticandPaediatricSciences,UniversityofPavia,Pavia,Italy

b_Shionogi_Italy,_Rome,_Italy

c_Department_of_Obstetrics_and_Gynaecology,_University_of_Torino_School_of_Medicine,_Ospedale_Mauriziano_Umberto_I,_Torino,_Italy d_Department_of_Obstetrics_and_Gynecology,_University_of_Modena,_Modena,_Italy

e_Department_of_{Neurosciences}_and_Reproductive_Sciences,_University_of_Naples_Federico_II,_Naples,_Italy

f_Obstetrics_and_Gynecology_Unit,_Department_of_Molecular_and_{Developmental}_Medicine,_University_of_Siena,_Siena,_Italy g_Department_of_Obstetrics_and_Gynaecology,_University_of_Cagliari,_University_Hospital_of_Cagliari,_Cagliari,_Italy

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received5April2016

Receivedinrevisedform31May2016 Accepted9June2016

Keywords:

Vulvarandvaginalatrophy Post-menopausalwomen REVIVEsurvey Sexualrelationships Vaginaldryness Dyspareunia

a

b

s

t

r

a

c

t

Objectives:ToachieveadeeperunderstandingoftheattitudesandperceptionsofItalianpost-menopausal

women(PMW)regardingvulvo-vaginalatrophy(VVA).

Studydesign:AspartoftheEUREVIVEstudy,anonlinesurveywasconductedinfourEuropeancountries;

theItalianarmcomprised1000participantsfromrepresentativeregionsofItaly.

Mainoutcomemeasures:Theperceptions,experiencesandneedsofItalianPMWinrelationtosexualand

vaginalhealth.

Results:ThemostfrequentVVAsymptomwasvaginaldryness(78%).Usually,theseverityofsymptoms

wassimilartoorworsethanwhentheyﬁrstappeared.Thiswasparticularlytruefordyspareunia,themost

bothersomesymptom(76%).VVAsymptomshadasigniﬁcantimpactonItalianparticipants’abilityto

achievepleasurablerelations(74%)andspontaneity(70%).Although75%ofparticipantswerestillsexually

active,theirsexdrivehadbeenreducedbyathirdbecauseofVVA.Womenexpectedthatdoctorswould

startadiscussionofmenopausalsymptomsandsexualhealth,butthiswasrarelythecase(11%).Most

womenhadbeentreatedwithavaginalover-the-counter(OTC)product.Womenwhohaddiscussed

theirconditionwithaphysicianweremorelikely(68%)tobeundertreatmentforVVAthanthosewho

hadnot(36%).Lowcompliancewasassociatedwithsymptomimprovement(23%),nothavingannoying

symptoms(22%),andtheimpossibilityifrestoringthevaginatonormal(14%).Commonreasonsfor

treatmentdissatisfactionwererelatedtorouteofadministrationordiscomfort.Lackofefﬁcacyand

fearofahormoneeffectwereperceivedasthemainlimitationsforOTCandlocalestrogenproducts,

respectively.

Conclusions:DespitethecommonnessofVVAanditssigniﬁcantimpactonqualityoflife,thecondition

remainsunderdiagnosedinItaly.Discussionofsymptomswithdoctorsinﬂuencesthediagnosis,and

patients’satisfactionwithavailabletreatmentsisnothigh.

BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

∗ Correspondingauthorat:ResearchCentreforReproductiveMedicine,Section ofObstetricsandGynecology,IRCCSPoliclinicoSanMatteo,PiazzaleGolgi2,27100 Pavia,Italy.

E-mailaddress:renappi@tin.it(R.E.Nappi).

1. Introduction

Vulvarandvaginalatrophy(VVA),alsoknownasGenital Syn-dromeofMenopause(GSM)[1,2]afterarecentbroaderdeﬁnition toincludeits globalimpactinuro-genital andsexualhealth, is achronicandprogressivepost-menopausalconditionassociated withthereductioninestrogenlevelsthatapproximatelyaffects 50%ofallpost-menopausalwomenworldwide[3–8].

http://dx.doi.org/10.1016/j.maturitas.2016.06.009

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R.E.Nappietal./Maturitas91(2016)74–80 75

TheVVAencompassesacomplexclusterofsymptomsthatmay varyaccordingtoage,durationofmenopause,frequencyof sex-ualintercourse,etc.Thepoorestrogenizationinuro-genitaland pelvictissuesmainlyresultsinvaginaldryness,irritation,lossof elasticity,decreasedlubrication,dyspareunia,andurinary symp-toms[3–8].PreviousEuropeanresearchhasshownthattheimpact ofVVAsymptomsinpost-menopausalwomenissignificant,since agrowingpercentageofthepopulationisagingandachievingtheir lastmenopauseperiod[9].Inadditiontoitsimpactonsexual func-tionandrelationshipwiththepartner,VVAcanhavesignificant influenceonmany dailyliving activitiesaswellas inwomen’s qualityoflife[2,10–12].

Asaconsequenceofthereportedpatient’sembarrassmentto askfor advice tohealthcare professionals (HCP) [10,12,13],the VVAclinicaldiagnosisandtreatmentisstillabridgeddespitethe highprevalenceand theconsiderableimpactoftheproblemin post-menopausal women [6,14].Thisunder-diagnosis turnsthe diseaseintoachronicandprogressiveconditioninmanycases[15]. Recently,differentcross-culturalsurveysontheimpactofVVAhave beenconductedonpost-menopausalwomen[14,16–21], suggest-ingthatVVAsymptomshaveasigniﬁcantglobalnegativeeffect onhealth,satisfaction,andsexualbehavior,despiteaccountingfor confoundingfactorsduetopopulationandculturalparticularities likethoseco-existinginEurope[22].

Theobjectiveofthepresentanalysis,basedontheREalWomen’s VIews of Treatment Options for Menopausal Vaginal ChangEs-Europe(REVIVE-EU)survey,wastoachieveadeeperunderstanding oftheVVAproblemknowledgebyItalianwomenaftermenopause, togetherwiththeirexperiencesandneedsintermsofsexualand vaginalhealth,aswellasthecurrentnatureoftheirinteractions withHCP.Thiswillhelp togain betterclinicaland therapeutic approaches,avoidingthemisconceptionsandspeciﬁcregretson estrogentherapythatusuallyjeopardizetheoptimizationofVVA management[6,23].

2. Methods

Followingthe same methodologyof the original US REVIVE survey, an online interview was conducted in several Euro-pean countries(Italy, Germany,Spain and United Kingdom)as describedpreviously[24].InItaly,ofatotalof7284women orig-inallyscreened,1000womenwithVVAsymptomswereincluded, beingdemographicallyrepresentativeofalltheItaliangeographic regions(North-East:19%,North-West:34%,Center:21%,South18%, Islands:8%).

The EUREVIVE survey wasoriginally translated and cultur-allyadaptedfromtheUSREVIVEversion(researchagency:Eikon Europe; panel used: Toluna Group), as well as pre-tested in a subsample of50 participantsbeforethebeginning ofthestudy period. The comprehensive online questionnaire was approved bythecorrespondingaccreditedinstitutional reviewboard.The surveyparticipantswereinformedof thestudyprocedures and gaveinformedconsenttoparticipate.TheEUREVIVEsurveylasted 35minandwasdesignedwithamarginerrorof3.1%atthe95% conﬁdenceinterval.Theinvitationtoparticipatewassenttothe targetpopulation(post-menopausalwomenwithatleastoneVVA symptomaftertheonsetofmenopause)bythepanel(selectedby agerange).Participation wascompensatedwithpointsthatcan thenberedeemedforvouchersorgadgets(butnotforproducts ormoney).Participantsenteredthesecureonlinequestionnaire portalandcompletedthesurveybetweenmid-Juneandmid-July of 2014. Prior tothe completion of the questionnaire a three-stepscreeningprocesswascompleted(seeFig.1forthesedetails in the Italian participants). The information and variables col-lectedfromtheparticipantsincluded:knowledgeaboutVVAand

Table1

BaselinecharacteristicsoftheItaliansurveyedpopulation.

WomenreportingVVAsymptoms(n) 1000 Age(years),n(%) 45–50 99(9.9) 51–55 325(32.5) 56–60 309(30.9) 61–65 186(18.6) 66–70 60(6.0) 71–75 21(2.1) Maritalstatus,n(%) Married 673(67.3) Divorced 85(8.5) Domesticpartnership 71(7.1) Single 79(7.9) Widowed 52(5.2) Separated 40(4.0) Education/Employment,n(%) Employed 430(43.0)

Universityeducationorhighera ₂₇₁_(27.1)

Children,n(%) None 186(18.6) One 287(28.7) Two 386(38.6) Three 110(11.0) Fourormore 31(3.1) Childrenlivingathome,n(%) 544(67.0) PriortreatmentforVVAsymptoms,n(%) 787(79.0) OTCproduct 651(65.1) Prescriptionmedication 26(2.6) PrescriptionandOTCincombination 64(6.4) CurrenttreatmentforVVAsymptoms,n(%) 575(58.0) OTCproduct 492(49.2) Prescriptionmedication 28(2.8) PrescriptionandOTCincombination 1(0.01)

a_Includes:_trade_training,_degrees_and_master’s_degrees;_OTC:_over_the_counter.

menopausalsymptomatology,interactionswithHCPswithrespect toVVAsymptomatology,impactofVVAsymptomsonsexuallife anddailylivingactivities,currentorprevioususeofOTCproducts prescriptiontreatmentsforVVA,andpatient’sattitudestowards treatments.

Eligiblepatientswerethosewhofulﬁlledallselectioncriteria andwhohadvaliddatafortheconsideredvariables.Therewasno imputationofmissingdata.Theanalysisconsistedofadescriptive statisticsreportsummarizedbyrelativefrequencydistributionsfor categoricalvariablesofthesurvey.

3. Results

3.1. Populationdistribution

Thebaselinedemographicsand clinicalcharacteristicsof the ﬁnalsampleof1000ItalianparticipantsaresummarizedinTable1. The50–60agerangewasthemostrepresenteddemographicgroup inthesample(63%).Amongthecohortofparticipantssurveyed (Fig.1), 442(44%) had experienced VVAsymptomsin thepast month. At the beginning of the survey, 575(58%) of all those included participantswith VVAsymptoms were receiving VVA treatment.

3.2. VVAknowledgeandawareness

InItaly,withinthecohortofparticipantsthatwereawareof itsVVAcondition,thisknowledgeandinformationcamethrough activeinternetsearching(40%),newspaper/journalpaperreading (21%),talkswithfamilyorfriends(20%),anddirectdiscussionswith theirHCP/pharmacist(17%).Intheoverallsample,21%oftheItalian participantshadbeenclinicallydiagnosedwithVVAandformally

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Fig.1. CharacteristicsoftheItaliansurveyedparticipants.

communicatedthatwaybyitsHCP,althoughthisratevaried geo-graphicallyreachingalmost30%inthecenterbutlessthan14%in thenortheastregion(␹2_test,_p_<_0.005).

3.3. VVAsymptomsandimpactonlife

ThemostfrequentsymptomoftheVVAconditioninsurveyed Italianpost-menopausalwomenatthemomentoftheinclusion wasvaginal dryness (78%), followed bydyspareunia (pain dur-ingintercourse)(31%),vaginalirritation(30%)andvaginal/vulvar tenderness(8%),withnosignificantdifferencesamongregions.A retrospectivesummaryof theonset of symptomsassociated or linkedwithVVAispresentedinFig.2.Mostparticipants(58%or more)reportedtheonsetofsymptomsduringthepost-menopausal period,althoughitvariedconsiderablyacrossmenopausestages dependingonthespecificsymptomatology.Vaginalirritationwas themostlikelysymptomtooccurbeforemenopause(16%),while vaginaldrynessandtendernesswerethemostlikelysymptomsto beginwithinthefirstyearaftermenstrualcessation(27%and26%, respectively).Theonsetofpainwithintercourseoccursacrossall themenopauseandpost-menopauseperiod,althoughitismost commonattheexactmomentofmenopause(28%)orduringthe subsequentyear(23%).

Themajorityofthecohortacknowledgedthatatthetime of thesurveytheseverityofsymptomswassimilarorworsethan whenit ﬁrstappeared(about 2/3ofcases),withparticular ref-erencetopainduringintercourse(75%),andwithoutdifferences amongcountryregions.Painassociatedwithsexwasratedasthe mostbothersomesymptom(76%participantssetitasbothersome orextremelybothersome),althoughallVVAsymptomswererated asquitebothersome.ParticipantsalsostatedthatVVAmadethem feelaging(45%),uncomfortable(37%),less feminine(16%), frus-trated(15%),worried(11%),anxious(11%) anddepressed(10%). ThemostconcerningfacetonmindreportedasaresultofVVA symptomswere“losingsexualintimacy”(47%)and“youth”(17%). ThehigherinterferenceofVVAsymptomswasacknowledgedby participantsonsexualsatisfaction(74%),followedbysexual spon-taneity(70%),intimacy(69%), andrelationshipwiththepartner (66%),respectively(Fig.3).

Italian participants who have a partner (81%) were cohab-itating in 85% of cases. The survey shows that 75% of Italian post-menopausalwomenwithVVAweresexuallyactiveduringthe

lastyear.Theanalysisshowedthatthestrengthofsexualdrivewas diminishedaround33%overall(␹2_test,_p_<_0.01)_as_a_direct_result

ofVVAsymptomatology(30%inwomenwithpartnerand49%in womenwithoutpartner).

3.4. InteractionwithHCP

Overall,96%of participantsreportedvisitinga HCPfor their main gynecological needs (91% of them having a gynecolo-gist/obstetricianand17%ageneral/familypractitioner).Overhalf ofHCPswerefemalephysicians(54%).Duringthelastyear,71% oftheparticipantsconsultedtheirmainHCP,withthehigherrate inthesouth(76%)andthelowerintheislandsandthenorth-east region(68%,inbothcases).Only41%oftheparticipantswithan HCPforgynecologicalneedsacknowledgedthattheirHCPusually askedaboutthatparticipant’ssexualactivityduringroutine check-upvisits.TwothirdsofItalianparticipants(67%)haddiscussedVVA symptomswiththeirphysician.Italianwomeninislandswerethe participantswholessdiscusssymptomswiththeirHCP(60%)and thoseinthenorth-westtheoneswhodomore(71%).Threequarters (75%)ofparticipantsreportedthattheyexpecttheirHCPto specif-icallyaskaboutmenopause-relatedsymptoms,althoughonly11% ofthemsaidthattheHCPthemselveshadinitiatedthe conversa-tion(rangingbetween8%inthesouthand13%inthenorth-west region).

Themostcommonlyreportedreasonsfor neverdiscussVVA symptomswithHCPwerebeliefsthattheconditionwasa natu-ralpartoftheagingphenomenon(36%),followedbythestatement thatsymptomswerenotbothersomeenoughtowarrant discus-sion withtheirHCP (25%) and that theywill goaway in time (24%).Almost53%oftheparticipantshadreceivedadvice/support fromtheirpartneraboutVVAtreatment.Usually,dependingonthe specificsymptom,between62%(vaginal/vulvardryness)and76% (tenderness)ofparticipantsdiscussedtheproblemwithaHCP dur-ingthefirst6monthsexperiencingit.Italianparticipantsreported overallsatisfactionwithhowHCPhandledthefirstdiscussionabout VVAsymptoms(70%),thereceivedinformation(67%)andthe treat-mentoptionsproposedbythephysician(64%).

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R.E.Nappietal./Maturitas91(2016)74–80 77

Fig.2. OnsetofVVAsymptomsinItalianwomencurrentlysufferingfromVVA.

Fig.3.VVAsymptominterferencewithsexuallifeandotheractivitiesinItaly.

3.5. ExperienceswithVVAtreatments

AmongthetotalItaliancohort,58%ofparticipantswere cur-rentlyusingaVVA-speciﬁctreatment(Fig.4).Theoverallincidence ofwomennaïvetoanytreatmentwas21%(lowerinthenorththan inthesouthregions,␹2_test,_p_<_0.05)_and_another_21%_had_lapsed

fromtheirtreatmentschedulewhenthesurveystarted.VVA treat-mentsweremainlyadministeredvaginallywithoutprescription (83%ofcurrentusers,mostlybenzocaineandcalendulaextract), whilevaginal prescriptiontherapies wereuncommon(3%), and an8%ofparticipantswereusingbothkindsofproducts(Fig.4). WomenwhohavediscussedtheirVVAsymptomswithanHCPwere morelikelytobeundercurrentmedication(68%vs.36%forthose whohadnotdiscussedsymptoms),aswellasthosewhohavebeen diagnosedfor VVA(94%vs. 75%).Participantsstarted theirVVA treatmentindifferentmanners:(1)23%throughaHCPprescription andtherecommendationofanOTCproducttobeusedtogether;

(2)15%startedusinganOTCproductthroughaHCPbefore receiv-ingspeciﬁcprescription;(3)12%begantreatmentthroughaHCP prescriptionwithoutpreciousOTCrecommendation;(4)another 12%startedusinganOTCproductbeforetalkingtoaHCP.

Anoverallratioof40%ofcurrentparticipantsabandonedtheir medicationatsomepointinthepast.Themostfrequentreasons forthislowcomplianceweretherelieffromVVAsymptoms(23%), notconsidersymptomsbothersomeenough(22%),thebeliefthat symptomswoulddiminishwithtime(15%),theinabilityof treat-menttoreverse thevaginal changes(14%) and thepriceof the product(13%).Inpatientswhocompletedorwerecurrentlytaking anOTCmedication,60%reportedoverallsatisfaction.Bycontrast, inpatientswhocompletedtheirlocalestrogenprescriptionorwho werecurrentlytakingit,51%showedglobalsatisfaction.

Italian participants also expressed their perception on VVA treatmentdifﬁculties(Table2).Usersof OTCmoisturizers were mainlyworriedabouttheimpossibilitytorestorethevaginainto

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Fig.4. Participant’streatmentuse.

Table2

ViewsofVVAtherapiesinItalianparticipantscurrentlyusingtreatment.

OTCpersonalvaginalmoisturizer(n=333) OTCvaginallubricant(n=77) Prescriptionvaginalproduct(n=32) Issuesrelatedtorouteofadministration,n(%)

Messy 36(10.8) 8(10.4) 4(12.5)

Notdiscrete 12(3.6) 0(0.0) 1(3.1)

Notanoralpill 24(7.2) 3(3.9) 2(6.3)

Donotliketouchingbody 10(3.0) 1(1.3) 0(0.0)

Issuesrelatedtoconvenience,n(%)

Interruptsmydailyactivities/life 5(1.5) 1(1.3) 0(0.0)

Inconvenienttoadminister 26(7.8) 5(6.5) 6(18.8)

Cannotbesexuallyspontaneous 45(13.5) 5(6.5) 1(3.1)

Difﬁcultdosingschedule 10(3.0) 2(2.6) 0(0.0)

Procedureofadministeringtreatment 13(3.9) 0(0.0) 2(6.3)

Issuesrelatedtosideeffects/safety,n(%)

Concernaboutbreastcancer 15(4.5) 1(1.3) 9(28.1)

Concernabouthormoneexposure 18(5.4) 2(2.6) 12(37.5)

Concernaboutlong-termusesafety 35(10.5) 8(10.4) 12(37.5)

Vaginaldischarge 21(6.3) 9(11.7) 4(12.5)

Concernaboutothersideeffects 30(9.0) 4(5.2) 11(34.4)

Experiencedsideeffects 7(2.1) 2(2.6) 1(3.1)

Partnerabsorbingestrogen 9(2.7) 1(1.3) 3(9.4)

Issuesrelatedtoefﬁcacy,n(%)

Vaginanotrestoredtonaturalstate 86(25.8) 19(24.7) 10(31.3)

Notenoughreliefofsymptoms 36(10.8) 4(5.2) 1(3.1)

Takesalongtimetostartworking 25(7.5) 7(9.1) 3(6.3)

Other,n(%)

Expensive 38(11.4) 8(10.4) 1(3.1)

Negativeimpactonintimacy 12(3.6) 1(1.3) 1(3.1)

itsnormalconditions(25.8%),buttheyalsohadconcernsrelatedto

itsimpactonsexualspontaneity(13.5%),thepriceoftheproduct

(11.4%),thelimitationonsymptomrelief(10.8%)andthemessy

administration(10.8%).ParticipantsthatusedOTClubricantswere

mostlyworriedbythelimitationsoftheproductinrestoringthe

natural state of the vagina (24.7%), the side effects of vaginal

discharge(11.7%), itsmessiness(10.4%),itscost(10.4%)andthe

safetyofalong-termuse(10.4%).Finally,womenthatweretaking

VVAprescriptionproductsweremostworriedaboutsafetyissues

includingthelong-termsafety(37.5%),hormoneexposure(37.5%),

othersideeffects(34.4%)andbreastcancerrisks(28.1%),aswellas

withtheabilityoftheproducttorestorethevaginatoitsnatural

condition(31.3%).

4. Discussion

The post-hoc analysis of the Italian branch of 1000

post-menopausal women with recognizable VVA symptomatology

includedintheEuropeanversionoftheREVIVEstudy–thelargest

surveyofthisnaturetodate(n=3768)–highlightedthestill

sig-niﬁcantlack of awareness of the VVAcondition bysubjects in

Italyandtheconsequencesforitseffectiveclinicaland

therapeu-tic management. A previousanalysis of theREVIVE survey has

detectedsigniﬁcantsocio-culturalbarriersinEuropefortheexact

VVAimpactinrelationwithpost-menopausalwomen’ssexual

sat-isfactionandspontaneity,aswellaswiththeirinteractionwith

HCP’s[22].Theseobservationstallyotherpreviousevidenceabout

thefactthatfemalesexualdysfunctionsoccuralongacontinuum fromdissatisfaction tocompletedysfunction linkedwith

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socio-R.E.Nappietal./Maturitas91(2016)74–80 79

culturalfactorsthatmaymodulatetheexpressionandcomplaining modalities[20,25].Signiﬁcantly,this healthvariationoccursnot onlyat acountrylevel, butalsoata regionallevel with signif-icantculturalorsocial differenceslikethose existingfor Italian regionsmorecentral-Europeandriveninthenorthandothersmore Mediterraneandriveninthesouth[26].

Aspreviouslyreportedinotherbackgrounds,theroleofvaginal drynessasoneofthemostsigniﬁcantVVAsymptomsassociated with menopause has been proved also here in Italian post-menopausalwomen[10,14,21,24].Symptomsgenerallyappeared earlyaftertheonsetofmenopauseandusuallydidnotresolveover time oreven worsened,even for Italianwomen that expressed higher treatmentsatisfaction than other Europeancountriesas evidencedbytheoverallEUREVIVEsurvey[21,24].Thefactthat only1/5ofthesurveyedwomeninItalywereformallydiagnosed withVVAandthatusuallytheylastformorethansixmonthsto discusssymptomswithaHCP,evidencedthatVVAisstill under-recognizedinthis country.Thisoccursinspiteofbeingdirectly associatedwithextremeburdenandwithprogressivebothersome symptomatologylikepainduringsexualintercourseandvaginal discomfortthatextremelycompromisessexualpleasureand spon-taneity[12,14,20,27].Thetrendtowardsanunderdiagnosewasalso depictedrecentlyinItalybytheAGATAstudygroupunderthemore wideperspectiveoftheGSMcondition[28].Infact,although

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of post-menopausalItalianwomeninoursurveyhaveacknowledged beingsexuallyactive,ourresultsshowedthat,afterVVA symp-tomsmanifestation,sexualdrivefalldownapercentageof30%in womenwithpartnerandalmosta50%inthosewithoutpartner. Thisobservationislikelyrelatedmainlywiththereductionof sex-ualsatisfactionthroughagingalsoreportedinItaly[29],aswell aswiththedemonstratedassociationofsexualfunctioninItalian womenwithoccurrenceofpainduringsexandwithsymptoms aftersexualintercourse[30].

TheEuropeanREVIVEsurvey hasindicatedthat theeffective discussionofsymptoms andcommunicationwithanHCPhasa significantimpactbothontheincidenceofthediagnosisofVVA andthetherapeuticapproach.Thispatternhasbeenalsoobserved specificallyfortheItalianpost-menopausalwomen.Inthissense, thedatainItalyprovesthatwomenwhohaveconsulteda gyne-cologistdiscussmoreeasilyVVAandmenopausalsymptoms,and startsooneramedicaltreatment.Concretely,inthiscountry,among participantswhohavediscussedtheirVVAsymptomswith physi-cians,thepercentage ofwomenundertreatmentalmostdouble thatobservedonthosewhodidnotdiscusssymptoms. Further-more,although2/3ofItalianparticipantsacknowledgedthathave discussedVVAwiththeirHCP,theystillexpecttheirHCPto initi-ateproactivediscussiononsymptoms(75%),afactthatveryrarely happens(onlyoneintencases,asimilarratethanfortheoverallEU REVIVEsurvey).Despitetheseobservationsprovetheneedforan improvedawarenessbyHCPsregardingVVAanditsimpact,both thepercentageofwomenwhodiscusssymptomswithanHCPand thepercentageofsymptomaticparticipantsformallydiagnosedare higherforItalianpost-menopausalwomenthatfortheoverallEU REVIVEcohort[24].Thisisinagreementwithpreviousresultsof theCLOSERsurvey,whichalsoshowedsignificantlyhigher wor-riesinSouthernEuropeanpostmenopausalwomenwithlong-term vaginaldiscomfortanditsimpactontheirsexualrelationships[20]. Regardingthetherapeuticmanagementof VVAinItaly,VVA treatmentswereadministeredmainlyvaginallywithout prescrip-tion(OTC),althoughtheefficacyandsafetyofminimallyabsorbed localvaginalestrogenasVVAtherapyhasbeenextensivelyproven [31,32].ItalyisoneoftheEuropeancountriesstudiedwithhigher rateofcurrentuserssinceonly anoverall1/5ofItalian partici-pantsremainednaïvetoanytreatment(32%inEUREVIVE)and2/5 hasleftitatleastoncepreviously(23%inEUREVIVE).Main rea-sonsthatexplainwhywomenhavehadstillarelativelylowlevel

ofcompliancewithvaginaltreatmentsweretheresultofa com-plexspectrumofculturalelements(perceptionofimprovement andof notenoughannoyingsymptoms)and skepticalviewson thereversibilityofvaginalchanges[22].InItaly,effectivenesswas perceivedasthemainlimitationforOTCproductswhileforlocal estrogenwasthefearofhormoneeffect.Foralltherapeuticoptions themostfrequentreasonfordissatisfactionwasrelatedtotheroute ofadministrationordiscomfort[22].

Themainlimitationsofthisanalysisareadirectconsequence oftheoriginalsurveynature,mainlythefactthatdatacamefrom anelectronicallyself-reportedquestionnairethatcouldbeaffected fromrecallbiaseffectandfromrespondentbiaswhenreporting subjectivesymptoms.Ontheotherside,theoverallItalian sam-pleincludedintheREVIVEsurveyrepresentsthelargestonenever included beforeabout VVAsymptomatology, being representa-tiveofthecurrentagestratiﬁcationoftheItalianpostmenopausal womenpopulation,aswellasoftheconditionanditsmanagement indifferentregionsinItalywithverydiversecultureintermsof sexualhealth[29].

Ourresultsdemonstratedthat,despitethecommonnessofVVA symptomsaftermenopauseanditssignificantimpactonqualityof lifeandsexualenjoyment,thisconditionremainsunderdiagnosed andundertreatedinItaly.Discussionofsymptomswithadoctorhas asignificantimpactontheincidenceofVVAdiagnosis,whilethe rateofdissatisfactionwithcurrentlyavailabletreatmentsremains relativelyimportant.Toeffectivelypromoteachangeofbehavior andofVVAperceptioninItalianwomen,bothpolicy-makersand cliniciansshouldconsiderthewaytosolvethedisputebetween expectationsandexperienceswithtreatments[33],togetherwith abalancededucationalprogramforpatientsaboutrealrisk-benefit profileofthecurrentlyavailableproducts.

Contributors

RENandMPdesignedthestudy.

REN,MP,NB,AC,CDC,SLandAMPdevelopedthemethodology. REN,NB,AC,CDC,SLandAMPsupervisedthecollectionofdata managedbyathirdparty.

MPperformedtheanalysis. RENwrotethemanuscript.

MP,NB,AC,CDC,SLandAMPcriticallyrevisedthemanuscript. Allauthorsgaveﬁnalapprovaloftheversiontobepublished. Conﬂictofinterest

RossellaE.Nappihadaﬁnancialrelationship(lecturer,member ofadvisoryboardsand/orconsultant)withBayerHealthCareAG, BoehringerIngelheim,ElyLilly,Endoceutics,GedeonRichter,HRA Pharma,MerckSharpe&Dohme,NovoNordisk,PﬁzerInc.,Procter &GambleCo.,ShionogiLimitedandTEVAWomen’sHealthInc.

MartireParticcoisanemployeeofShionogiItaly.

NicolettaBigliahadaﬁnancialrelationship(lecturer,memberof advisoryboardsand/orconsultant)withGedeonRichter,Shionogi LimitedandItalfarmaco.

CostantinoDiCarlohadaﬁnancialrelationship(lecturer, mem-berofadvisoryboardsand/orconsultant)withBayerHealthCare AG,GedeonRichter,HRAPharma,MerckSharpe&Dohme,Shionogi LimitedandTEVAWomen’sHealthInc.

AngeloCagnacci,StefanoLuisiandAnnaMariaPaolettideclare noconﬂictofinterest.

Funding

Financial support for the REVIVE Survey was provided by ShionogiLimited.

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Ethicalapproval

Thecomprehensiveonlinequestionnairewasapprovedbythe correspondingaccreditedinstitutionalreviewboardsatthe respec-tiveinstitutions(UniversityofPavia,UniversityofTorinoSchool ofMedicine,UniversityofModena,UniversityofNaplesFederico II,UniversityofSienaandUniversityHospitalofCagliari).All sur-veyparticipantswereappropriatelyinformedofthenatureofthe studyandgaveinformedconsenttoparticipatebeforecompleting theonlinequestionnaire.

Provenanceandpeerreview

Thisarticlehasundergonepeerreview. Acknowledgements

The authors would like to thank Emili González-Pérez (TFS Develop),ScientiﬁcAdvisorandMedicalWriter,forhisassistance withmanuscriptpreparation.Sponsorshipandarticleprocessing chargesforthisstudywerefundedbyShionogi,Inc.

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