Combination of Treatments With or Without Surgery in Localized Provoked Vulvodynia: Outcomes After Three Years of Follow-Up

ORIGINAL RESEARCH ARTICLE Open Access Combina ion o T ea men s Wi h o Wi hou Su ge y in Localized P o oked Vul odynia: Ou comes A e Th ee Yea s o Follow-Up Anu Pauliina Aal o, 1,2, *Heini Huh ala, 3 Johanna Ma¨enpa¨a¨, 1,4 and Synno¨ e S a 1,4 Mos ul odynia pa ien s ecei e combina ions o se e al ea men modali ies o hei ch onic pain ul condi- ion. I conse a i e ea men s ail, es ibulec omy is conside ed o be he ul ima e ea men op ion o local- ized p o oked ul odynia (LPV). The aim o his desc ip i e s udy was o analyze elie o pain, quali y o li e (QoL), and complica ions associa ed wi h combining su ge y wi h conse a i e ea men s among LPV pa ien s, bo h in sho e m and a e 3 yea s o ollow-up. The s udy popula ion consis ed o a e ospec i e pa ien coho o su gically (n=16) and only conse a i ely (n=50) ea ed LPV pa ien s. QoL da a we e assessed by a alida ed ques ionnai e (RAND-36). Da a we e col- lec ed by e iewing pa ien eco ds and by aid o pos al ques ionnai es. E ficacy o ea men s in elie o pain was measu ed by nume ical a ing scale (NRS). Two mon hs a e su ge y, he NRS sco es assessed by a physician we e lowe in he su ge y g oup han in pa ien s ea ed only conse a i ely ( p=0.008). Howe e , a e a median o 36 mon hs o ollow-up, sel - epo ed NRS sco es and QoL showed no di e ence be ween he wo pa ien coho s. Complica ion a e a e es ibulec omy was 18.8%. The findings sugges ha combining su ge y wi h conse a i e ea men s may esul in a mo e e ec i e sho - e m educ ion o pain. Howe e , he e ec seemed o be only empo a y, as no long- e m benefi was achie ed. Keywo ds: quali y o li e; RAND-36; es ibulec omy; ul odynia; ul odynia ea men In oduc ion Vul odynia is a ch onic pain synd ome o unknown e iology a ec ing 7–8% o women in popula ion- based epidemiological s udies. 1,2 Vul odynia is usually desc ibed as bu ning, s abbing, i ching, s inging, and eeling o i i a ion. The 2015 Consensus and Te - minology and Classifica ion o Pe sis en Vul a Pain and Vul odynia 3 di ides ul a pain in o wo ca ego ies. Thefi s ca ego yincludes ul a pain ha iscausedbya specific clea ly iden ifiable diso de (e.g., pain caused by geni al he pes). The second ca ego y includes ul a pain ha is a leas 3 mon hs in du a ion and canno be clea ly iden ified o linked o a specific cause. Howe e , i may ha e po en ial associa ed ac o s. The desc ip o s o he pain a e loca ion (local, gene alized, and mixed), ype (p o oked, spon aneous, o mixed), onse (p ima y and seconda y), and empo al pa e n (in e mi en , pe sis- en , cons an , immedia e, and delayed). Symp oms can o e lap and co-occu . Vul odynia may be associa ed wi h a his o y o yeas in ec ion, ho monal ac o s, ge- ne ic ac o s, pel ic floo dys unc ion, and psychological ac o s. 3 The mos common clinical sub ype o ul a pain in p emenopausal women is localized p o oked ul ody- nia (LPV). 4 LPV is also conside ed o be he mos com- mon o m o sexual pain in women <30 yea s o age. 5 1 Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, Tampe e, Finland. 2 Depa men o Obs e ics and Gynecology, Kan a-Ha ¨me Cen al Hospi al, Ha ¨meenlinna, Finland. 3 Facul y o Social Sciences, Uni e si y o Tampe e, Tampe e, Finland. 4 Depa men o Obs e ics and Gynecology, Tampe e Uni e si y Hospi al, Tampe e, Finland. The abs ac o his s udy was p esen ed a he XXIV Wo ld Cong ess o ISSVD, A gen ina, in Sep embe 2017. *Add ess co espondence o: Anu Pauliina Aal o, MD, Depa men o Obs e ics and Gynecology, Kan a-Ha ¨me Cen al Hospi al, Ah enis on ie 20, Ha ¨meenlinna 13530, Finland, E-mail: anu.aal o@ho mail.com ªAnu Pauliina Aal o e al. 2019; Published by Ma y Ann Liebe , Inc. This Open Access a icle is dis ibu ed unde he e ms o he C ea i e Commons License (h p://c ea i ecommons.o g/licenses/by/4.0), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. BioResea ch Open Access Volume 8.1, 2019 DOI: 10.1089/bio es.2018.0044 BioResea ch OPEN ACCESS 25 Ch onic pain is known o ha e a nega i e impac on a woman’s quali y o li e (QoL). 6,7 Di e en medical ea men modali ies o LPV con- sis o local, opical, o o al medica ions. Pa ien s ea- ed by a mul idisciplina y eam a e usually o e ed physio he apy (including anscu aneous elec ical ne e s imula ion), sexual counseling and he apy, and psycho he apy. Al hough a mul idisciplina y ap- p oach o LPV is ecommended, 8,9 i is ac ually no e - idence based. 10 Su ge y ( es ibulec omy) o LPV is ecommended as he ul ima e ea men op ion, i con- se a i e ea men s ail o a e insu ficien in e ms o pain educ ion. Based on s udies conce ning su gical ea men o LPV, epo ed success a es a y be ween 60% and 90%, 11 e en hough he compa ison o di e en s udies is di ficul as he e m ‘‘success,’’ he su gical echnique used and he leng h o ollow-up show conside able a - ia ion. 11 The e is no defini i e consensus as o which su gical echnique is he supe io one. In a e iew by Tommola e al., 12 which was based on 33 s udies on su gical ea men o LPV (o ul a es ibuli is), i was concluded ha he expe ience o indi idual su - geons plays an impo an ole, and ha he aim o su ge y should be o emo e all pain ul issues while a oiding unnecessa y isks. The e iew also ound su - ge y o be e ec i e and sa e. 12 Mos s udies on su gical ea men o LPV lack an- domiza ion and/o con ols. One o he ew andom- ized con olled s udies on es ibulec omy is ha by Be ge on e al., 13 which showed ha es ibulec omy was mo e success ul han su ace elec omyog aphic eedback and g oup cogni i e-beha io al he apy in pain educ ion. As he au ho s s a ed, he e is a conce n in in e p e ing hese esul s, due o a highe p e ea - men d op-ou a e in he es ibulec omy g oup. 13 Howe e , he psychological and sexual unc ions emained equally posi i e in all h ee g oups a e 6 mon hs o ollow-up. Ano he s udy ha included an- domiza ion o he su gical (beha io al ea men and su ge y) and nonsu gical (beha io al ea men only) g oups, by Weijma Schul z e al., 14 ound no di e ence in he ou comes be ween hese wo ea men modali- ies a e a mean o 2.5–3 yea s o ollow-up. In he e- iew o Golds ein e al., 11 su ge y was ecommended o LPV a e ailu e o conse a i e ea men s (le el B e idence). In p e ious s udies conce ning su ge y o LPV, he measu ed ou comes ha e a ied. A leas pain educ- ion, 13,15 dyspa eunia, 13,16 sexual unc ioning, 13 psycho- logical dis ess, 15 and pa ien sa is ac ion 16 ha e been measu ed using ques ionnai es; mo eo e , findings o physical examina ion and sel - epo ed symp oms ha e also been epo ed. Psychological well-being, 17 quali y o sexual li e, 17 and sexual and pa ne ship sa is ac ion ha e all been epo ed o imp o e 18 a e es ibulec omy. The aim o his s udy was o e alua e he sa e y and e ec i eness o LPV ea men s wi h o wi hou su - ge y in bo h sho and long e ms. Pain was measu ed by nume ical a ing scale (NRS) assessed by bo h a physician and he pa ien . QoL was e alua ed a e a combina ion o ea men s wi h o wi hou su ge y, using a ques ionnai e (RAND-36) alida ed in he Finnish popula ion. Ma e ials and Me hods This e ospec i e coho s udy on LPV pa ien s was ca ied ou a he Depa men o Obs e ics and Gyne- cology o Tampe e Uni e si y Hospi al (TAUH), Tampe e, Finland. All a leas 18-yea -old women diag- nosed wi h ul odynia a TAUH om Janua y 2003 o May 2016 we e sc eened o he s udy. Po en ial ul o- dynia pa ien s we e iden ified om he hospi al eco ds (compu e da abase) by using he app op ia e ICD-10 codes: N90.9 (noninflamma o y diso de o ul a and pe ineum, unspecified); N90.8 (o he specified nonin- flamma o y diso de s o ul a and pe ineum); N94.1 (dyspa eunia); and N94.2 ( aginismus). Only LPV pa- ien s who ulfilled he s ic c i e ia by F ied ich, 19 o se e e pain on es ibula ouch o a emp ed aginal en y, and ende ness on localized p essu e wi hin he ul a es ibule, we e conside ed eligible (n=66). Among hese eligible pa ien s, 16 pa ien s ope a ed on o LPV ( es ibulec omy) we e iden ified. Pa ien s wi h gene alized o con inuous ul a pain we e ex- cluded. O he exclusion c i e ia included malignan umo s o ul a and ongoing inflamma o y o de ma- ological diseases o ul a. The flow cha o s udy pa- ien s is shown in Figu e 1. In o ma ion on pa i y, menopausal s a us, age, di e - en ea men modali ies, and complica ions a e su - ge y was collec ed om he hospi al’s medical eco ds. The baseline pain be o e any ea men s o LPV was assessed by a physician wi h a co on swab es and a ed on an NRS om 0 o 10. I he a ing was no ound in he pa ien eco d, he in o ma ion was epo ed as ‘‘no da a.’’ As a pa o he ea men p o o- col, e e y pa ien had a checkup appoin men a 2 mon hs a e he su gical ea men wi h he ope a ing su geon. Pa ien s ea ed wi h conse a i e me hods Aal o, e al.; BioResea ch Open Access 2019, 8.1 h p://online.liebe pub.com/doi/10.1089/bio es.2018.0044 26 only we e assessed by a physician usually a e 2 o 3 mon hs a e commencing he ea men s. The conse - a i e ea men modali ies used o LPV a e desc ibed in Table 1. The su gical echnique used was he modified pos e- io es ibulec omy desc ibed by Tommola e al., 16 wi h he aim o su gically emo e he pain ul ul a a ea. The ope a ions we e pe o med unde gene al anes hesia, and all ope a ions we e ca ied ou by h ee senio gyne- cological su geons. Fi s , 0.01% lidocain cum ad enalin solu ion was injec ed in o he ul a es ibulum o bleeding con ol and p e en ion o pos ope a i e pain. To excise es ibula mucosa, 2-mm deep incisions using elec ocau e y we e made om 10 o 2 o’clock in he pos e io ul a es ibulum o a wid h o *1– 2 cm. The inne incision was made jus inside he hy- menal ing, and he ou e ma gin ollowed he Ha ’s line. The aginal mucosa was libe a ed om unde lying issue and subsequen ly opposed o dis al ul a ma gin wi h abso bable su u es wi hou ension. A se en-page pos al ques ionnai e on demog aphic da a, sel - epo ed pain, and RAND-36 was sen o he 66 eligible LPV pa ien s. The ques ionnai e was e- sen o he pa ien s who did no e u n he ques ion- nai e wi hin 2 mon hs a e he fi s mailing. The alida ed Finnish e sion o he RAND-36-i em heal h su ey includes eigh mul i-i em dimensions: gene al heal h, physical unc ioning, men al heal h, so- cial unc ioning, i ali y, pain, and physical and emo- ional ole unc ioning. 20,21 Pa icipan s o he s udy we e mo eo e asked o as- sess ul a pain in ensi y upon ouch on he NRS be- o e and a e ea men s. NRS was used o quan i y he in ensi y o ul a pain by a ing he pain using a 0- o-10 scale, whe e 0 indica es ‘‘no pain’’ and 10 indi- ca es ‘‘ he wo s pain imaginable.’’ The s udy p o ocol was app o ed by TAUH E hical Commi ee (5APR2016, Iden ifica ion Code R16053), and a w i en in o med consen was ob ained om he pa ien s pa icipa ing in his s udy. Ve sion 23 o IBM SPSS s a is ics so wa e was used in s a is ical analyses (IBM SPSS S a is ics o Win- dows, Ve sion 23.0. IBM Co p. 2015. A monk, NY). Mann–Whi ney U- es was used o s a is ical compa - isons. A p obabili y alue o p<0.05 was conside ed as s a is ically significan . Resul s Thi y-six pa ien s (55%) e u ned he ques ionnai e du ing he s udy pe iod (Augus 2016–No embe 2016). Twen y-eigh pa ien s e u ned he ques ionnai e a e he fi s mailing and eigh pa ien s a e he second mailing. The pa ien flow cha is shown in Figu e 1. The esponse a e o pos al ques ionnai es in he nonsu gical g oup was 46.0% and ha in he su gical g oup was 81.3% ( p=0.020). Demog aphic da a and pain be o e and a e he ea men s a e shown in Table 1. A he da a analysis poin 1 (2 mon hs a e commencing he ea men s), he su gical and nonsu gical g oups di - e ed significan ly in age ( p=0.048). The median ollow-up ime a he da a analysis poin 2 was 36 mon hs (in e qua ile ange [IQR] =24–36). The mos equen ( ecei ed by >50% o he pa ien s) combina ion o conse a i e ea men s consis ed o local ea men s (lidocaine and/o gabapen in), physio he apy, and sex- ual counseling in bo h pa ien coho s. The ea men modali ies used o bo h pa ien g oups a e summa ized in Table 1. A he da a analysis poin 1, he nonsu gical and su gical ea men g oups did no di e wi h espec o any ea men modali y. Howe e , a he da a analysis poin 2, he wo ea men g oups di e ed wi h espec o he equency o sexual counseling (Table 1; p=0.03). A da a analysis poin 1, median p e ea men NRS sco es we e simila be ween nonsu gical (i.e., combina- ion o ea men s wi hou su ge y) and su gical g oups FIG. 1. Pa ien flow cha . Aal o, e al.; BioResea ch Open Access 2019, 8.1 h p://online.liebe pub.com/doi/10.1089/bio es.2018.0044 27 (median NRS sco es 9 in bo h g oups, p=0.11, Table 1). Median pos - ea men NRS sco e assessed by a physi- cian in di e en ea men g oups was 7 and 2, espec- i ely ( p=0.008). A e median o 36 mon hs o ollow-up, sel - epo ed NRS sco es be o e o a e ea - men s did no di e significan ly be ween he g oups (p=0.66 and p=0.18, espec i ely, Table 1). A da a analysis poin 2, we also compa ed medical eco d- de i ed da a assessed by a physician. Physician-assessed NRS sco e be o e ea men in he nonsu gical g oup was 8 and ha in he su gical g oup was 9 ( p=0.014). Simila ly, pos - ea men NRS sco e assessed by a physi- cian was 7 and 2, espec i ely ( p=0.005). Among he LPV pa ien s who did no espond o pos al ques ion- nai es (n=30), he median p e ea men NRS sco e col- lec ed om he pa ien eco ds was 9 (IQR=8–9.5, missing da a n=13), and he median 2-mon h pos - ea men NRS sco e was 5 (IQR =2.25–8, missing da a n=14). When non esponde s we e compa ed wi h all LPV pa ien s who e u ned he ques ionnai e (da a analysis poin 2), he p e- and pos - ea men NRS sco es de i ed om he medical eco ds we e sim- ila ( p=0.291, p=0.592, espec i ely). The QoL a e a median o 36 mon hs o ollow-up a e ea men sdidno di e significan lybe ween he su gical and nonsu gical g oups in any o he eigh mul i-i em dimensions (Table 2 and Fig. 2). Ou o 16 pa ien s ope a ed on, 3 had complica- ions a e su ge y, esul ing in a complica ion a e o 18.8%. One pa ien had hea y pos ope a i e pain and Table 1. Demog aphic Da a and T ea men s Gi en o Localized P o oked Vul odynia Pa ien s Da a analysis poin 1 (Fig. 1). Re iew o medical eco ds Da a analysis poin 2 (Fig. 1). Re iew o medical eco ds and pos al ques ionnai e All LPV pa ien s Combina ion o ea men s wi hou su ge y Combina ion o ea men s wi h su ge y p a All LPV pa ien s Combina ion o ea men s wi hou su ge y Combina ion o ea men s wi h su ge y p a Numbe o pa ien s 66 50 16 N/A 36 23 13 N/A Age, median (IQR) 28 (25–33) 27 (24–32.3) 30.5 (26.5–38.3) 0.048 28.5 (25–32) 27 (24–29) 29 (26.5–33) 0.06 Nullipa ous, % (n) 95.5 (63) 94 (47) 100 (16) 0.32 86 (31) 82.6 (19) 92.3 (12) 0.48 P emenopausal, % (n) 98.5 (65) 100 (50) 93.8 (15) 0.08 100 (36) 100 (23) 100 (13) 1.00 NRS be o e ea men s, asked om pa ien s a he ime o he co on-swab es 9 (7.25–9), n.d. n=22 9 (7–9), n.d. n=18 9 (8–9.5), n.d. n=4 0.11 9 (7–9), n.d. =9 8 (7–9), n.d. n=7 9 (8–10), n.d. =2 0.014 NRS a e ea men s, asked om pa ien s a he ime o he co on-swab es 5 (2–8), n.d. n=24 7 (4–8), n.d. n=19 2 (2–4), n.d. n=5 0.008 5 (2–7), n.d. n=10 7 (4.5–8), n.d. =7 2 (2–4), n.d. =3 0.005 Sel - epo ed NRS be o e ea men s in he pos al ques ionnai e N/A N/A N/A N/A 8 (8–9) 8 (7–9) 8 (8–9) 0.66 Sel - epo ed NRS a e ollow-up in he pos al ques ionnai e N/A N/A N/A N/A 3 (2–5.75) 4 (3–6) 2 (2–5) 0.18 T ea men s ecei ed by LPV pa ien s Local ea men s, b %(n) 100 (66) 100 (50) 100 (16) 1.00 100 (36) 100 (23) 100.0 (13) 1.00 TCA o an icon ulsan c 15.2 (10) 12.0 (6) 25.0 (4) 0.21 16.7 (6) 13.0 (3) 23.1 (3) 0.35 Physio he apy (including TENS) 90.9 (60) 92.0 (46) 87.5 (14) 0.59 88.9 (32) 91.3 (21) 84.6 (11) 0.46 Sexual counseling by a ained nu se 75.8 (50) 80.0 (40) 62.5 (10) 0.16 77.8 (28) 87.0 (20) 61.5 (8) 0.03 Topical ea men s d 22.7 (15) 18.0 (9) 37.5 (6) 0.11 19.4 (7) 8.7 (2) 38.5 (5) 0.050 Local injec ions o he pain ul si e e 16.7 (11) 16.0 (8) 18.8 (3) 0.80 11.1 (4) 8.7 (2) 15.4 (2) 0.76 a p- alue be ween su gical and nonsu gical g oups. b Lidocaine gel o he pain ul a ea in ul a 30 min be o e in e cou se o gabapen in 6% c eam applied wice a day o he pain ul a ea o 6–8 weeks. c Ami ip yline 10–40 mg mos commonly used TCA o p egabalin 150–300 mg. d Podophyllo oxin (5 mg/mL) applied locally o ende poin s o es ibulum a e 5% ace ic acid applica ion. T ea ed a ea was co e ed wi h a mild es ogen c eam and co e ed wi h gauze pads un il he nex day. e 2–4 mL o be ame asone and long ac ing anes he ic agen (bupi acaine), bo h 50% and 50%, injec ed submucuously o he pain ul si e. IQR, in e qua ile ange; LPV, localized p o oked ul odynia; N/A, no applicable; n.d., no da a; NRS, nume ical a ing scale; TCA, icyclic an ide- p essan ; TENS, anscu aneous elec ical ne e s imula ion. Aal o, e al.; BioResea ch Open Access 2019, 8.1 h p://online.liebe pub.com/doi/10.1089/bio es.2018.0044 28 was eadmi ed o hospi al on he hi d pos ope a i e day. Two mon hs a e su ge y, he pa ien was s ill su - e ing om pain, whe eas a e 1 yea o ollow-up he pain in he ul a a ea was ‘‘ ans o med in o a neu o- pa hic pain,’’ and he pa ien was ea ed wi h pe o al gabapen in, which esul ed in su ficien pain elie . Ano he pa ien was eadmi ed a e 7 days o su ge y, because o a pa ial wound dehiscence. The wound was epo ed o ha e healed comple ely a he 2-mon h ollow-up isi . The hi d pa ien su e ed om se e e pain igh a e su ge y, and had o s ay o e nigh a he hospi al. A 2-mon h ollow-up, he pain sco e was assessed as ‘‘0’’ by he ope a ing physician. Discussion We desc ibe he e a e ospec i e coho o 66 LPV pa ien s ea ed a ou ins i u ion. We e alua ed sho - e m su gical complica ions, pain, and QoL o nonsu - gically and su gically ea ed pa ien s fi s a e 2 mon hs and hen a e a median o 36 mon hs o ollow-up. QoL a e 36 mon hs did no di e when compa ing he su gically and only conse a i ely ea- ed g oups in any o he eigh QoL dimensions o al- ida ed RAND-36 ques ionnai e. Addi ion o su ge y o he conse a i e ea men s esul ed in lowe NRS sco es measu ed by a physician 2 mon hs a e su ge y. Howe e , he e was no di e ence in sel - epo ed NRS pain sco es measu ed a e he longe ollow-up. Table 2. Quali y o Li e A e Follow-Up in Di e en RAND-36 Dimensions Combina ion o ea men s wi h su ge y Combina ion o ea men s wi hou su ge y p a Physical unc ioning/ heal h, mean (SD) 95.4 (15.20) 92.4 (14.45) 0.243 Physical ole unc ioning, mean (SD) 84.6 (33.13) 69.6 (43.92) 0.278 Emo ional ole unc ioning, mean (SD) 66.7 (40.82) 56.5 (46.53) 0.498 Vi ali y, mean (SD) 58.1 (16.65) 51.5 (23.95) 0.518 Gene al men al heal h, mean (SD) 68.9 (22.87) 65.7 (21.77) 0.416 Social unc ioning, mean (SD) 79.8 (19.46) 72.3 (27.94) 0.485 Pain, (SD) 75.2 (26.76) 64.7 (24.50) 0.144 Gene al heal h pe cep ions, mean (SD) 63.9 (21.03) 62.2 (23.88) 0.974 a p- alue be ween su gical and nonsu gical ea men g oups. SD, s anda d de ia ion. FIG. 2. Quali y o li e o LPV pa ien s measu ed wi h RAND-36. LPV, localized p o oked ul odynia. Aal o, e al.; BioResea ch Open Access 2019, 8.1 h p://online.liebe pub.com/doi/10.1089/bio es.2018.0044 29 Ves ibulec omy seems o be a sa e ea men modali y o LPV wi h an accep able complica ion a e. This is in line wi h he p e ious e iew by Tommola e al. conce n- ing su ge y o LPV. 12 In his s udy, su ge y was associ- a ed wi h be e sho - e m ou comes in e ms o pain a e 2 mon hs o su ge y. P e iously, i has been shown ha medianpainmeasu edwi hVASdec eases om 8 o 2 in su gically ea ed pa ien s, 18 which is o a magni ude simila o ou esul s. Howe e , assessmen o pain a he checkup isi s sho ly o a any ime poin a e su ge y by he a ending su geon is no blinded and ce ainly a isk o many ypes o bias. This bias may also explain he di e ences shown he e be ween NRS alues ob ained om medical eco ds and hose epo ed by pa- ien s hemsel es. In a andomized s udy, 14 su gical in- e en ion added o beha io al app oach had ou come simila obeha io alapp oacha e 2.5–3yea so ollow-up. A simila ou come was ound among pa ien s gi en an oppo uni y o choose be ween su ge y and no su ge y.Al hough hesamplesizein hes udywassmall (n=14 in he andomized pa o he s udy), i being a andomized s udy s eng hens he pe cep ion ha indi- idual ailo ing o ea men is one o he key ac o s in a success ul ea men o LPV. We epo he e QoL da a ob ained wi h a alida ed ques ionnai e among su gically and nonsu gically ea ed ul odynia pa ien s. The e was no di e ence in QoL be ween hese wo pa ien g oups a e a me- dian o 3 yea s o ollow-up. P e iously, Bohm-S a ke and Rylande ha e epo ed ha es ibulec omy im- p o es QoL measu ed by VAS om median 0.5 o 6.5, du ing a median 41 mon hs o ollow-up. 17 How- e e , ano he long- e m ollow-up s udy on LPV pa- ien s ea ed conse a i ely e sus ea ed su gically ailed o show any di e ence in long- e m well- being be ween he ea men g oups. 18 E en i he e a e p e ious aluable epo s on QoL and o e all well-being among es ibulec omy pa ien s, 17,18 o ou knowledge his is he fi s epo using a alida ed QoL ques ionnai e when assessing QoL among es i- bulec omy pa ien s. The e a e some limi a ions o ou s udy. The s udy is a e ospec i e non andomized c oss-sec ional s udy. An ideal s udy se ing would ha e been a com- pa ison be ween only su gically and nonsu gically ea ed pa ien s p e e ably as a andomized con- olled s udy. A con ounding ac o is ha he s udy pa ien s in he su gical g oup had also ecei ed a i- ous conse a i e ea men s be o e su ge y, ha is, he compa ison be ween he g oups is in ac a com- pa ison be ween combina ion o ea men s wi h and wi hou su ge y. Because bo h g oups ecei ed a i- ous conse a i e ea men modali ies i is no possi- ble o conclude ully he e ec i eness o su ge y. Howe e , his se ing is clinically una oidable since es ibulec omy is he ea men modali y o e ed o pa ien s only a e ailu e o all nonin asi e ea - men s. The ac ha pa ien s we e asked o epo pain e ospec i ely a e a median o 36 mon hs a e ea men s con ains also a isk o bias. Howe e , he median ollow-up ime a e ea men s did no di e significan ly be ween su gically and nonsu gi- cally ea ed pa ien s ( p=0.35) and QoL measu ed co esponded o p esen momen (i.e., he ime o ques ionnai e). A longi udinal QoL e alua ion, done be o e and a e ea men s, would ha e been o addi- ional alue. Al hough he o al numbe o pa ien s is ela i ely low, wi h he su gically ea ed g oup being e en smalle , i eflec s he ac ha ul odynia is a a he a e condi ion. The esponse a e a e ollow-up was only sa is ac o y, 55%. The esponse a e o pos al ques- ionnai es o su gically ea ed pa ien s was highe and his may lead o a alse accen ua ion o posi i e e ec o he in e en ion, ha is, o a ype I e o . Howe e , pain a ed on he NRS and QoL did no di e signifi- can ly be ween he g oups a e he longe ollow- up. The amoun o missing da a was un o una ely also qui e high and his may cause bias. The s udy pa- ien s had ecei ed sligh ly di e en conse a i e ea - men en i ies be o e su ge y o du ing he ea men pe iod ha migh ha e an e ec on ou come, oo. Conclusion Measu ing QoL wi h a alida ed ques ionnai e in he Finnish popula ion can be conside ed as s eng h o he s udy. Bea ing in mind he limi a ions, as dis- cussed ea lie , we conclude ha e en i su ge y seems o be associa ed wi h mo e e ec i e pain man- agemen in he sho e m, i showed no addi ional benefi wi h espec o QoL o pain a e ex ended ollow-up. In con as , i may be concluded ha pe - o ming es ibulec omy a e conse a i e ea men s is sa e and does no seem o be ha m ul. Howe e , long- e m pa ien - epo ed ou comes in e ms o QoL and pain a e su ge y do no seem o di e om hose achie ed conse a i ely. Conside ing e- cen e idence o a s ong placebo e ec conce ning medical ea men s, 22 p ospec i e su ficien ly pow- e ed con olled ials a e uly wa an ed. Aal o, e al.; BioResea ch Open Access 2019, 8.1 h p://online.liebe pub.com/doi/10.1089/bio es.2018.0044 30 Acknowledgmen This s udy has ecei ed unding om he Compe i i e S a e Resea ch Funding o he Expe Responsibili y A ea o Tampe e Uni e si y Hospi al. Au ho Disclosu e S a emen The au ho s (A.P.A., J.M., and S.S.) epo conflic o in e es s. 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Ci e his a icle as: Aal o AP, Huh ala H, Ma ¨enpa ¨a ¨J, S a S (2019) Combina ion o ea men s wi h o wi hou su ge y in localized p o- oked ul odynia: ou comes a e h ee yea s o ollow-up, BioRe- sea ch Open Access 8:1, 25–31, DOI: 10.1089/bio es.2018.0044. Abb e ia ions Used IQR ¼in e qua ile ange LPV ¼local p o oked ul odynia N/A ¼no applicable n.d. ¼no da a NRS ¼nume ical a ing scale QoL ¼quali y o li e TAUH ¼Tampe e Uni e si y Hospi al TCA ¼ icyclic an idep essan TENS ¼ anscu aneous elec ical ne e s imula ion VAS ¼ isual analogue scale Publish in BioResea ch Open Access -B oad co e age o biomedical esea ch -Immedia e, un es ic ed online access -Rigo ous pee e iew -Compliance wi h open access manda es -Au ho s e ain copy igh -Highly indexed -Ta ge ed email ma ke ing liebe pub.com/bio es Aal o, e al.; BioResea ch Open Access 2019, 8.1 h p://online.liebe pub.com/doi/10.1089/bio es.2018.0044 31