Aim. In this study we evaluated the shortterm effects of vaginal erbium laser WEL)in the treatment of postmenopausal women(PMW) suffering from genitourinary syndrome of menopause (GSM).Methods. Sixty-five PMW were evaluated before and after VEt treatment (1 treatment

every 30 days, for 3 months). GSM symptomswere evaluated either with subjective (Visual Analog Scale, 1/AS) and objective (VaginalHealth Index Score, VHIS) measures. In adthtion, in 21 of these PMW suffering frommild-moderate stress urinary incontinence(Sul), the degree of incontinence was evaluated with the International Consultation onIncontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-U1 SF) before andafter VEt treatments.Results. VEt treatment induced a significantdecrease of VAS of both vaginal dryness, dyspareunia (P’cO.OI) and a significant (P<O.01)increase ofVHIS). In addition, VEL treatmentinduced a significant (P<OO1) improvementof ICIQ-SF scores in PMW suffering fromSUI. 1/EL was well tolerated with less than 2% of patients discontinuing treatment due toadverse events.Conclusion. 1/EL treatment significantly improves vaginal dryness, dyspareunia andmild-moderate SUI. Larger and long-termstudies are needed to investigate the roleof laser treatments in the management ofGSM.

Kr WORDs: Meqi ‘pause - Ato p1w — Urinary inconhinence, stress.

ORIGINAL ARTICLESMINrIa\ GINECOI. 2111i;67:97-1112

‘Deparnient of Obstetrics a ;,d G’nvco/c ,I’, P/sn()iire;’sitj’ Hospital. P/sn, Italy

—Vepartanoit n/obstetrics and GiiwcnlogiCl/inca Aleniaiia, (iiiieiu/net Del Desarro/lo

Sa lii (11/40, Ci He

The genitounnarv syndrome of menopause (GSM) is the new clehnition for

the variety of menopausal symptoms asso—

dated with physical changes of [1w vulva.vagina, and lower urinary tract, related withestrogen deficiency. I The symptoms relatedto GSM include vaginal dryness. burning.irritation, lack of lubrication, dvspareunia,as well as urinary symptoms of urgency’,dysuria and recurrent urinafl tract nicelions) The signs and symptoms of GSM affect LI to 50% of postmenopausal women(PMW): they are chronic and are expectedto worsen over time, interfering with sexual function and duality of lil’e.2d 1-lormonereplacement therapy (1-IRT) induces ellative. rapid and long-term reliet with the glocal vaginal estrogen administration thetreatment of choice for the sole treatmentof vaginal atrophv. 11 Although systemicrisks have not been identified with localIow-potencWlow-dose estrogens, long-termefficacy and safety data are lacking. In addition, many women do not accept extendedHRT, or may have contraindications, as apersonal history of breast canceL’ 0 Newmanagement strategies for GSM are neededin order to enable women lo choose among

Short-term effect of vaginal erbium laseron the genitourinary syndrome of menopause

M. GAMBACCIANI I, M. LEVANCINI .2

motto

Rh cc

E es

grafta

er cut

Cc rrcsponding :iuilic,r: M. Ganit,:iuc iani, Deparunenc of0li,acuics and Gyncttlugv. Fia Univursihv I lospit:iI. ViaI{cnn:i 67, 56100 ‘is:,, lE:ily E—mail ciiargarnl’:i@cin ii

Vol. ‘7- Nc,. 2 MINEItVA GINI:CoI.OGICA 97

C AMI3ACCIA NI SI 0 I4’r”FFRM F FFFCF OF \ A( I N A I FRI ill 1M I.ASFR ONTI IF G FNrI’OtJnl N,Ufl’ SY 50110 M F 01: ML: 501 I’S F

dillerent options, considering the benefitsand risks associated with each strategy.

Sal’atore / a/) reported that a treatmentwith the microahiatne carbon dioxide (CO,)laser max’ improve vaginal health in PMW.This seminal paper actually discloses a newem for non—hormonal treatment of GSM. Indeed. we have to consider that various lasers possess diverse properties, that can heusefully applied in different conditions. Thenon—ablative Erbium laser technology may

provide a non—invasive treatment option,and it is widely used for surgical treatmentsin dermatology, dentistry and aesthetic medicine. ‘lO The aim of the present studs’ wasto evaluate the short—term effectiveness andacceptability of vaginal erbium laser ( VEL ) asa new, second generation, non—ablative pho—tothennal therapy for the treatment ol GSM.

Materials and methods

This study was perlorlfled in 67 PMW suf—lering from GSM attending the outpatientMenopause Clinic of Pisa University 1-lospi—tal. ihe protocol was approved hy the IDivi—sion Ethics Committee and reviewed by anIndependent National Advisory Hoard. In—elusion criteria were: the presence of a GSMin healthy postmenopausal women (at least12 month since last menstrual perh )d r bilateral ovariectomv) with plasma gonado—tropin and estradiol levels in the postmen—opausal range (PSI 1>10 U/L; estradiol <25pg/mL) and negative PAl smear. Exclusioncriteria were vaginal lesions, scars. activeor recent (30 days) infections of the geni—touonary tract; abnormal uterine bleeding:use of vaginal preparations within the 30days prior to the study: history of photosen—sitivitv disorder or use of photosensitizingdrugs; genital prolapse (grade lll—IV according to the Pelvic Organ Prolapse Quantification. PO[’—Q. system classification); seriousor chronic condition that could interferewith study compliance: treatment with hormones to relieve menopausal symptoms inthe 12 months before the study.

At the first visit the eligibihin’ of the palientwas verified, the written informed consent

was obtained, and the sociodelnographicand clinical characteristics were collected.Subjective symptoms (vaginal dn’ness andclvspareunia ) were evaluated b a VisualAnalog Scale (VAS) at even’ visit (range 0-10cm. 0=tota I absence of the sviiiptoin and 10cm = the worse possible symptom). In addition, at each visit during the gvnecologicexamination the \iginal I-lealth Score IndexVITIS) \T1-l1S evaluates the appearance of

vaginal mucosa (elasticity, p1’1 vaginal discharge. mucosal integrity and moisture).Each parameter is graded from 1 to 5 beingatrophic a total score 1 5)

All patients gave a written inlormed consent All subjects were treated with VEL. anon—ablative solid slate Erbi tim in yttriumaluminum-garnet crystal (Er;AG I Laser (Fotona Smooth Thi xs, Fot n;i . Ljobhjana, Slov—enia) with a wavelength of 29-rO nm. Theparameters were selected based on extensive preclinical and clinical studies controlling the energy and pulse duration simultaneously.2’ This technology (SMOOTIfMmode) with a sequence of low Ruence andlonger—shaped Erbium pulses, distributes theheat approximately 100 microns deep ilitomucosa surface, achieving a controlled deepthermal effect, without ablation. Therefore,the SMOOTI-l’ mode ptlses’lIosv controlled tissLie heating, in a safe and harmless ambulatory procedure without ablationand carbonization of the tissues, practicallyavoiding die risk of perloration with accidental lesions of urethra, bladder or rectum,The laser parameters ( RenovaLase®, Phase1) are settled to deliver 8,5 j of laser energywith the Smooth mode pulsing sequenceusing 7 mm spot. I3rieflv. alier inserting aspecifically designed vaginal speclllum, theprobe is inserted into the speculuin. withno direct contact with the vaginal mucosa.Thus circular irradiation of vaginal wall isperformed with laser energy delivered every 5 mm (using the graduated scale on theprobe). retracting the probe till the vestibule.This procedure is repeated 3 times rotatingthe spectiltim by 4S each time. Finally, ;ilierremoving the spertlltlm and using a differentprobe, the vestiliu le and introit are irradiatedwith a fractional 7 mm Smo al i mode laser

MINFIrVA oINErol.or;IFA April 2(115

p

SI(OIt’I’-i’FI(SI EFTECI OF VAGINAl, FI1I1IFM LASER (IN lYlE GENriOURINARY SYNDROME OF MENOPAISE ( AMIIACCIANI

beam, delivering 3J of laser energy. Such laser beam is manually scanned aroLind vestibule and introitus with slight overlappingof individual spots until three passes are executed (RenovaLase®, Phase 2). After treatment, patients are recommended to avoidsex inLercout-se for one week. Twenty one ofthese patients were suffering also from stressurin;in incontinence (SUI) and the degree ofincontinence was assessed with the International Consultation on Incontinence Ques—tionnairetrinan Incontinence Short Formlc:lQ—l.l SF), where a inaximtitn score of 21

represents permanent incontinence. None ofthese patients presented a pelvic oian pro

lapse greater than stage II, according to thePelvic Organ Prolapse Quantification ( POP—

Q ) system classification. These littielits during the VEL procedures were submitted alsoto additional laser treatment ol anterior vagi

nal wall ( lncontiLtse Phase I pincedure ),specifically designed for urinan incontinence. with a Iract k ma ted Sim t t h m )debeam, delivering 3J of laser energy.

The VEL procedures were perlortllecl inan outpatient clinical setting. No specificprepauon, anesthesia, or post treatmentmedications were prescrilecl. Before theprocedi.n’es the vagina was cleaned with aswab. Patients were treated with 3 laser apphcations, (Li, L2, L 3) every 30 clays, withscreening visit 2 to -i weeks prior the firstlaser treatment (baseline) and IhIlow up ‘is—its after 4 weeks from the last laser applica—tion (T+4), The women were asked to evaluate the acceptability of the therapy. Womenwere asked to assess the general acceptability, efficacy of the finalized therapy as excellent, good, acceptable, bad, or ii nacceptable.Being an exploratory study, the sample sizewIs not based on a statistical rationale. Thesample size was planned to be similar tothose of published data.t All the results arereported as the mean±SE of iIsolite values.

Age (years) 62.9±8.1Age :11 menopause 33±S. 1Years since nenup time 1 3.5±1.-inods’ mass index (Iqtnm2 27.3±2.3

5; I I lU/i.) 7i-t± lOBtsir;itliiiI ( pg/mt.) 23t±i 3

es within and between the groups. respectivelv. The post hoc comparison was made

by Scheffe F-test, using the Sigma Stat Viewsoftware (Sl’SS Science, Chicago, TL, USA).

Results

The age. age at menopause and ‘earssince menopause. l3ody Mass Index I SMIand basal hormone levels are reported inTable I. A total of GS patients completedthe stttclv; one patient left the study for personal re;tsnns; One complaining the discom—‘ott related to the first application. The VASscores for vaginal dryness and dvspareuniashowed a significant (P<O.OI ) decrease ‘I

Eli- Dyspareunia

Figu ft I . — Fifed of seen ii LI gen er;i t it in ti 5cr ilieriu oWe’—

ape on vaginal dryness tA) and dyspareunia (It) (ft=63).‘<t) (It is. orrcsp{ nd ing I,: sal il ties: see [ext for de—

‘Inced.mcIual1-10

10adgicJex

ofusFe).ing

T,uu.r I —Baseline ci,amck’rtclic,c o/65 partici/xuhIsecho conipleeetl I/it’ sun)’. Data are LnpIL&SSL’d as aI) I L’( I, I tSl)

on -

I.lnl

Fo01.—

fheenrol-RI I—

1’in cIthentoepre,

on—rm—ionallycci-1111.

asergynceL4 I

heith)sa.

I is‘ye-

—

Vaginal dryness

Z

bI%ii

treitmert, F&bw’ iw..k

the.ile. Slat is/ica/ aiialnisingftertntted5cr

1013 \[,I. (C. Ni 2

tails.

Baseline values were compared 1w Stu—

dent’s t—test. Two way analysis ol variancefor repeated measures and factorial analysis

of variance were used to test the diflerenc—

AIINiI(\:\ C,I.SECI)I.O(ICA

a

99

-

rGMIIIACCIANI SIICIUVIERM EFFECT OF VACTNAL FRIIIUNI LASER ON TilE GFNHOl’IlINAIO SYNDROME OF NIENOI’Al’SF

Figure 2.— El feet of second generation laser I liermi uher

;Ipv on \Tffl5 (N=65)P<i) I) I s. orresp{ ,n ding ,as;I I va I ucs in both grot, p5:

see text for details.

weeks after VEL treatment (Figure 1). Thedifference from baseline values for drynessand dvspareunia was statistically significant(P<0.01) during the follow—Lip period (Figure 1). In addition also the VEIlS significant

ly (P<0.01) increased (Figure 2). The valuesmeasured 4 weeks from the last VEL application were significantly (p<O.O5) differentfrom corresponding basal values (Figure 2).

In the 21 patients suftering Irom SLII theVEL treatment induced a significant C P<0.01decrease in the [CIQ-SF scores (Figure 3).

The ICIQ-SF scores remained significanlly(p<O.O 1) lower than basal values at T÷4(Figure 3).

The results of this prospective study mdi—care that VEL treatment can ameliorate thesigns and symptoms of OSM. The reduciionin the subjective scores and the objectiveimprovements were rapid and evident after the first laser application. VEL treatmentwas well tolerated by women who subjectively perceived a rapid clinical benefit thatwas confirmed by the objective improvement of the vaginal milieu, as measured bythe VEIlS. Salvatore ul ci/. demonstratedthat the microablative C02 laser energy iseffective to improve vaginal dryness as wellas dyspareunia, in a 12 weeks follow—tipstudy. Our data clearly indicates that alsothe Erbium laser is effective in the therapyof GSM, as previously reported in abstractkirm.1° As with the CO pn )cedure, our

r

VHIS

In the 65 valid completers in the VELgroup, 55 patients (84.6 %) defined the procedure excellent-good, 7 patients (10.7%) acceptable, 3 patients (i .6 %) reported their experience as bad, only [(Jr the first application.

TO Ii LI U T.4

Irtatments Follownsp Iw..Isi

Discussion

ICIQ-SF

J

16

14

12

10a,oSUU,

6

4

2

0

*

T I T

TO Li

1II

L2

Ltreatments

L3

100

T +4

Figure 3.—Efleci of second generation laser ilsermot her:tpv on International consultation on incont hence Questionmitre (ICIQ- SI) score in 21 l’MW suffering twill stress urinary incontinence.9’<O.O I tv corresponding basal values: see text br details.

Follow-up (weeks)

STINIRcA olNEcoLocicA .\pril 201i

-

s[ioIti’-I’ERM EiFECr OF VAGINAl. EltitlUNi LASER ON’iII GENi1OtItINAIlY syNonraul OF MENOPAUSE C AM It ACCIANI

two—step protocol the laser irradiation wasapplied first into the vaginal canal and afterat the introitus area. At variance, the VELprocedure is performed using special vaginal speculum introduced as a guide for thehandpiece laser beam delivery system. Thus,the patients rio not feel the several longiwdma! passes performed using a step-by-stepretraction of the handpiece. No anesthesiawas necessary and only 3 prns reportccl the first laser application experience asbad. Conversely, after the first treatment,VEL effects on vaginal mucosa induced anideal treatment compliance. The innovativetechniques used in the VEL procedures canguarantee not only the efhcacv. but also.mainly, an intrinsic safety, since the Erbiumbeam cannot damage the tissues in depth.eliminating the risk of tissue necrosis. in anon—ablative form, without cut. abrasion orbleeding. 16. 1 This characteristic makes Erbium laser an ideal candidate for the thermal treatment of the vaginal walls. 16-20 Inaddition, as previously reported by otherauthors,lT2, our data suggest that MEL treatments can be of help in PM\V sulieringfrom mild—moderate SLI. In fact, in PMWsuffering from GSM referring also mild tomoderate SUE, the MEL improved the ICIQSF scores. The MEL technique allows severalpasses on the vaginal canal that are necessary for the treatment oF the anterior vaginalwall in women suffering from St.]. The VELteclrnique. with a controlled rise in tissuetemperature, induces vasodilation and collagen remodeling and neocollagenesis. 1

Since the \‘EI. technique is conthirtalile forthe patient. the use of high fluences withhighly collimated fractionated beams is welltolerated. With the VEL the vaginal anterior wall is treated with several l’ thatcould not be possible without anesthesia,in an outpatient setting if the patients weresuffering from the procedure. The effect ofVEL on 5121 is of particular interest. Urinaryincontinence is a common and importanthealth care problem that is underreported,underdiagnosed, and therefore undertreat—ed in women. The treatment of 5121 isa major challenge for women’s health and qualfly of life. Nonpharmacologic management

for 512!, such as pelvic floor muscle training is effective, can improve UI and mayprovide complete continence, hut manypatients discontinue the treatment. Presentdata confirm that MEL might he useful forthe noninvasive treatment of SUE. 1520 Our

study has several limitations, including thesample size, but mainly the absence of asham, blank treatment. Olwiousk futLirewell—designed and controlled studies areneeded to validate the use of MEL for SLTI.

‘Al SE

theHontive

lentcc

thatwe

I l’ttedy isveIl-uptlso.Lpy

ractour

Conclusions

Taken together. these data clearly suggestthat MEL can he offered as a new, secondgeneration. non—ablative ph )totherlnal ther—apv br the treatment of OSM. Further studies will help to better define the role of MELfor the treatment of GSM and 511.

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v01. 67 - No, 2 MINIiHVA GINECOt.OCICA 101

— r

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Aft her Di Ilaher RI ci a!. on behalf of tile InterIM-Ui ma I NI e no pa use Soc jet;. I ‘pda ted 2013 inc ern:I t ci in —

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stk,dv. Cli n;,cterjc 201n;17- 1—7.12. kaulmann H, IIil,st B. Pulsed crl,ut,m: AU laser

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Stress Urinary Inconlinence ISUI I in \Xinien. IUGA.

Mae 21)13, Dul,linI ‘). Fist on it’ I. FrI ‘ihi m laser trea to tent thr e: ri y stages of

stress urban’ incontinence I St.JI I intl vaginal relax:,

tints signibic:itiIlv improves pelvic floor ftincti,in. 13th

(‘I ingress ol lb sian Reprod tul it in, NI a rcli 2013, Ve nice.

2(1, I_ce NI N l’reac n’ent of sag n a I relaxat it in syntl a Mite

ss ith an Fri jilIlSi: lAG laser using 90’ and 360’ scan

ning St opes a pilro sctcdv & shtrt-iercn resolis. L,scr

user 20I’i:23:129-38.

Gin/lit? nj ink’a:ci.—Doring the past 2 years, Dr Cam

butt i:, n i had Pits:, ftc ía I ‘el:, iorsli ps ulcctt, rer. ,nenil,er ,i

:,this,,rv hoards ;,ciukor i t,nstilt:,tit I U itli Bayer Pltartiia,

Merck Sh:irpc & I), ,hci:e, l’hzer list. teva 1itcr:,,nex - Dr I.e.

ant in i rep’ ,rtcci nii inflict t if i Illere.’.

-lcknonIddç’u’,ne,,u would like Iii th:,nkthe Director :,nd the Stall of the Casa di Cura San Russc,re,

I’is:i, for ,ssi5tIn(L’ in th,e c,sntpleIic’ts of thu study.

NtlNI-:Rs•\ CINI COi.OG CA

CAM ITACCIANI SilO WI’—’FER;t F prEci’ 0’ MAC tNi\ I. I’ It I Itt I B t_ASIER ON ‘N I F CENT lOt RI NARY SIN I IRONIc OF NI ENOI ‘At SE

.1

102April 21)1 S

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