Number of vaginal lactobacilli in postmenopausal women with vaginal atrophy before and after treatment with erbium YAG laser, a randomized sham-controlled trial

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Secondary objectives: To evaluate the effects of erbium YAG laser on vaginal atrophy symptoms and vaginal pH in postmenopausal women. Materials and Methods: A total of 44 postmenopausal women meeting inclusion criteria were randomized in laser group (n=22) and sham group (n=22). Vaginal lactobacilli grading, vaginal pH, vaginal atrophy score and vaginal atrophy symptoms (dryness, irritation, soreness, dyspareunia) wereassessed before and after treatment with erbium YAG laser for 2 consecutive times, 4 weeks interval; the results were compared with the effects of sham procedure. Any adverse events after the treatment were recorded. Statistical analysis was performed by using SPSS program and p < 0.05 was considered statistically significant. Results: 44women were included and 5were lost to follow-up. Compared with sham procedure, there was an improvement of vaginal lactobacilli grading in laser group (5/20 in laser group and 1/19 in sham group). However, the improvement did not reach statistically significant (adjusted OR = 5.32, 95%CI = 0.5-56.21). Vaginal atrophy symptoms measured by VAS and vaginal pH were improved in both groups without statistically significant difference between groups. Vaginal “dryness” VAS and vaginal atrophy score after treatment were significantly lowered in laser group compared to sham group. Conclusions: This study showed an improvement in vaginal lactobacilli grading after vaginal laser treatment. However, the difference of vaginal lactobacilli grading after treatment in both groups did not reach statistically significant. Erbium YAG laser Vaginal lactobacilli Randomized sham-controlled trial Menopause Vaginal atrophy Vaginal pH Figures Figure 1 Introduction Vaginal atrophy or genitourinary syndrome of menopause is commonly found in postmenopausal women. As many as 50% of postmenopausal women suffered from vaginal atrophy symptoms. 1 This condition is caused by low estrogen level after menopause. 2 The diagnosis of vaginal atrophy is clinical diagnosis which are vaginal dryness, irritation, pain, dyspareunia and urinary symptoms. 3 Treatments of vaginal atrophy can be either local hormonal treatment or non-hormonal treatments. Currently, vaginal estrogen therapy is one of the standard treatments of vaginal atrophy. However, caution was suggested in hormone sensitive cancer survivors. 4 Moreover, number of patients denied hormonal treatment. This leads to choices of non-hormonal treatments including vaginal erbium YAG laser. Vaginal laser is a novel treatment for vaginal atrophy. There are two types of laser used for intravaginal therapy – CO 2 and erbium YAG laser. 5 The advantage of erbium YAG laser is that it has 15 times more water absorption than CO 2 laser causing less penetration, faster tissue healing phase, fewer side effects and lesser pain compared with CO 2 laser. 4 The effect of vaginal laser is thermal effect to vaginal epithelium resulting in an expression of heat-shock proteins which stimulate growth factors activities, neovascularization, neocollagenesis, extracellular matrix formation and increase vaginal thickness and elasticity. However, thermal effect of erbium YAG laser is less than that of CO 2 laser causing no tissue damage. 4 Many prospective studies reported that vaginal erbium YAG laser can improve vaginal atrophy symptoms and its effect can be compared with vaginal estrogen therapy. 6 – 8 A systematic review and meta-analysis of laser therapy for genitourinary syndrome of menopause publish in 2017, included 14 studies of both CO 2 and erbium YAG laser, showed that vaginal laser improved all genitourinary syndrome of menopause (GSM) symptoms, female sexual function index (FSFI), vaginal health index score (VHIS) and vaginal maturation value (VMV). However, the quality of evidences was “low” or “very low” because there was no randomized sham-controlled study that can decrease the bias and placebo effect. 5 Vaginal lactobacilli are normal vaginal flora that can produce antimicrobial compounds such as hydrogen peroxide and lactic acid, and compete with pathogens for vaginal adherence. 9 Number of vaginal lactobacilli increases after vaginal epithelial maturation because of an increase of glycogen storage in superficial vaginal epithelium. 10 – 11 Therefore, it can be used as an objective measurement of vaginal atrophy. A prospective study of vaginal CO 2 laser and vaginal flora reported a significant increase of vaginal lactobacilli and a significant decease of vaginal pH after 3 applications of CO 2 laser. 9 However, there was no study to date about the effect of vaginal erbium YAG laser and number of vaginal lactobacilli. This study aimed to measure the effect of vaginal erbium YAG laser on number of vaginal lactobacilli. Besides, we also evaluate vaginal pH, vaginal atrophy symptoms and adverse effects after vaginal erbium YAG laser treatment. Material And Methods This randomized sham-controlled study was conducted at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand, between May 2019 and September 2020. The target population were postmenopausal women attending gynecology clinic or gender health clinic with vaginal atrophy symptoms (dryness, dyspareunia, irritation, pain). Inclusion criteria were postmenopausal women with at least one symptom of moderate to severe vaginal atrophy and age more than 40 years. (Moderate to severe vaginal atrophy was defined by the most bothersome symptom score at least “2” in at least one vaginal atrophy symptoms (0 = no symptom, 1 = mild, 2 = moderate, 3 = severe). Exclusion criteria were history of hormonal therapy, vaginal lubricants, vaginal moisturizers or spermicide in previous 3 months, active or recent genitourinary tract infection in previous 1-month, abnormal vaginal bleeding, genital organ prolapse stage at least II, history of vaginal surgery in previous 3 months and previous vaginal laser treatment. For sample size calculation, two independent proportions formula was used. The sample size was calculated using data from our pilot study. The proportion in study group and control group were 0.4 and 0.9 respectively. (Outcome for sample size calculation was proportion of participants with grade 1 vaginal lactobacilli after vaginal erbium laser treatment and after sham operation) Using 5% type I error and 20% type II error, the calculated sample size was 17 per group. Adding 20% drop out, total of 42 participants were needed. After completed written informed consent, all participants were interviewed to collect demographic data and randomized into laser group and sham group using block of four randomization with sealed enveloped. Participants in laser group were treated with erbium in yttrium aluminum-garnet crystal (Er:YAG) laser (Fotona Smooth™ XS, Fotona, Ljubljana, Slovenia), wavelength of 2940 nm, spot size 7 mm, frequency 1.6 Hz, laser energy 6.0 J/cm2 2 applications every 4 weeks. Participants in sham group were treated with 2 sham operations every 4 weeks. Sham operation was done while patient was in lithotomy position and placed an exactly the same equipment of vaginal erbium laser, but there was no laser energy from the equipment. A duration of sham operation was equal to that of vaginal erbium laser treatment or about 5 minutes. All participants were appointed for follow-up visit 4 weeks after the second laser or sham application. Vaginal atrophy symptoms were measured by visual analog scale (VAS) in every visit. Vaginal swabs were collected from posterior fornix and vaginal pH was measured using pH indicator strip applied to lateral vaginal wall. Vaginal atrophy score, as shown in Table 1 , was assessed in every visit. The vaginal swabs were sent to a microbiologist to evaluate the vaginal lactobacilli grading. Vaginal lactobacilli were reported into 4 grades according to number of lactobacilli per high power field. (grade 1: 50/HPF) All participants were blinded during the study period. All vaginal swab slides were sent to a microbiologist with identification numbers that did not mention about study group. Therefore, a microbiologist who evaluated vaginal lactobacilli grading was also blinded. Table 1 Assessment of vaginal atrophy score Not present (0) Mild (1) Moderate (2) Severe (3) Dryness Normal lubrication Slightly decreased Minimal lubrication Dry Rugae Normal number and depth Reduced rugae Rare rugae Smooth vagina Pallor Normal pink Light pink Very pale White/deep red Petechiae None Bleeds on scraping Bleeds on contact Clearly seen Mucosal elasticity Normal decreased None Stenosis This study was funded by Ratchadapisek Sompot fund and was approved by Institutional Review Board of Faculty of Medicine, Chulalongkorn University. Statistical analysis was performed by SPSS version 22.0. For descriptive statistic, Number, percentage and mean ± standard deviation (SD) was used for continuous data while number and percent were used for categorical data. For analytical statistic, ANOVA repeated measures and Friedman test were used for continuous and categorial data, respectively. An overall statistical significance was considered when the p -value of < 0.05. Results Total 44 participants were recruited and randomized to 22 in laser group and 22 in sham group. As 5 of them were lost to follow-up, total 39 participants were completed (the detail was shown by consort diagram in flow chart 1). Table 2 shows similar baseline characteristics of participants in laser group and sham group except for “age” that participants in laser group were younger than those in sham group (mean age in sham group was 60.4, mean age in laser group was 55.5). There was no significant difference in parity, menopausal age, year since menopause, baseline vaginal atrophy symptoms measured by VAS, baseline vaginal pH and baseline vaginal atrophy score between participants in both groups. There was no significant difference of BMI between two groups. There were similar baseline vaginal lactobacilli between laser group and sham group. The most presenting symptom of participants was dyspareunia (54.5% in both groups). Table 2 Baseline characteristics of the subjects in laser group and sham group Laser group (mean ± SD) Sham group (mean ± SD) p value Age (year) 55.5 ± 7.6 60.4 ± 6.6 0.03 Parity 1.5 ± 1.0 1.8 ± 1.1 0.47 Menopausal age (year) 47.3 ± 4.3 49.7 ± 5.3 0.10 Year since menopause (year) 9.0 ± 6.4 10.7 ± 7.1 0.41 Vaginal atrophy symptoms (VAS) 17.5 ± 8.6 16.3 ± 7.5 0.62 Vaginal pH 6.3 ± 1.4 6.6 ± 1.2 0.35 Vaginal atrophy score 6.5 ± 2.9 7.9 ± 2.9 0.13 Laser group N(%) Sham group N(%) p value BMI 1.00 < 18.5 1(4.5) 0(0) 18.5-24.99 12(54.6) 13(59.1) 25-29.99 7(31.8) 7(31.8) ≥ 30 2(9.1) 2(9.1) Lactobacilli grade 0.55 1 17(77.3) 21(91) 2 2(9.1) 1(4.5) 3 1(4.5) 0(0) 4 2(9.1) 1(4.5) Most symptoms 0.27 Dryness 8(36.5) 4(18.3) Dyspareunia 12(54.5) 12(54.5) Irritation 1(4.5) 5(22.7) Pain 1(4.5) 1(4.5) Table 3 shows vaginal lactobacilli grading in each visit of both groups. Visit 1 is pre-treatment. Visit 2 and 3 are after 1st and 2nd treatment respectively. In the laser group, grade of vaginal lactobacilli was higher significantly after 2nd treatment (p = 0.02). However, there was no statistically significant change of vaginal lactobacilli after 2 sham procedures. To compare between groups, using logistic regression for calculation of odd ratio (OR) of improvement after 2 laser treatment, adjusted OR for age was 5.32 (95%CI = 0.5–56.21, p = 0.17). Therefore, compared with sham group, the improvement of vaginal lactobacilli grading of participants in laser group was not reach statistically significant. Table 3 Vaginal lactobacilli grading, vaginal atrophy symptoms (VAS), vaginal atrophy score, vaginal pH in each visit of participants in laser group and sham group Laser group Sham group Lactobacilli grade Grade 1 Grade 2 Grade 3 Grade 4 Grade 1 Grade 2 Grade 3 Grade 4 Visit 1 15 2 1 2 17 1 0 1 Visit 2 16 0 1 3 16 2 0 1 Visit 3 13 1 1 5 17 1 1 0 p value 0.02 0.72 Vaginal atrophy symptoms (VAS) Laser group (mean ± SD) Sham group (mean ± SD) Visit 1 17.5 ± 8.6 16.3 ± 7.5 Visit 2 10.5 ± 8.7 13.8 ± 8.9 Visit 3 6.8 ± 5.5 10.0 ± 8.2 p value < 0.001 0.08 Vaginal atrophy score Visit 1 6.5 ± 2.9 7.9 ± 2.9 Visit 2 4.3 ± 2.1 6.6 ± 2.3 Visit 3 3.9 ± 2.4 5.6 ± 1.9 p value < 0.001 < 0.001 Vaginal pH Visit 1 6.3 ± 1.4 6.6 ± 1.2 Visit 2 6.0 ± 1.3 6.6 ± 1.2 Visit 3 6.1 ± 1.2 6.2 ± 1.1 p value 0.20 0.15 Vaginal atrophy symptoms, which were measured by visual analog scale (VAS), were significantly decreased after treatment in laser group. However, there was not statistically difference of vaginal atrophy symptoms after sham operations. Table 3 also demonstrates that vaginal atrophy score after treatment were significantly lowered in both laser group and sham group (p < 0.001). There was no statistically significant difference of vaginal pH before and after treatment in both groups (p = 0.20 and 0.15 in laser group and sham group, respectively). To determine secondary outcomes, mixed effect multiple linear regression was used and showed that there was significant change in vaginal dryness (mean change = -2.28, p = 0.01) and vaginal atrophy score (mean change = -1.49, p = 0.03) before and after treatment in laser group as compared to sham group. The changes of vaginal pH, total vaginal atrophy symptoms, pain, irritation and dyspareunia were not reach statistically significant. The secondary outcome results are shown in Table 4 . For the adverse event, only one participant in sham group complained about pain during operation but it was improved after the operation. Table 4 Secondary outcome adjusted with time and age due to imperfect randomization Outcome Mean change p value 95% CI VAS -2.73 0.15 -6.44 to 0.98 Dryness -2.28 0.01 -4.11 to -0.46 Irritation -0.36 0.57 -1.64 to 0.91 Soreness -1.18 0.07 -2.44 to 0.08 Dyspareunia -1.50 0.09 -3.22 to 0.22 Vaginal atrophy score -1.49 0.03 -2.82 to -0.16 pH -0.0 0.86 -0.61 to 0.51 Discussion Vaginal erbium YAG laser is a novel treatment for vaginal atrophy or, newly termed, genitourinary syndrome of menopause (GSM). The literatures showed effectiveness and safety of intravaginal laser therapy while erbium YAG laser is considered as the safer choice as compared to fractional CO 2 laser because of its non-ablative effect. 4 – 8 Mechanism of action of erbium YAG laser is photothermal effect to vaginal epithelium causes superficial tissue shrinkage, neovascularization, neocollagenesis results in vaginal tissue thickening and increases vaginal elasticity. 4 In the literature, there are few studies reporting an improvement of vaginal atrophy symptoms after vaginal erbium YAG laser treatment. 6 – 8 However, there was no study about vaginal erbium YAG laser and vaginal lactobacilli which can be used as an objective measurement. Vaginal lactobacilli are vaginal normal flora that dynamically changed with vaginal maturation and play a role in maintaining vaginal acidity and compete with pathogens. 9 , 10 , 12 To our knowledge, this study is the first randomized sham-controlled study to assess the effect of vaginal erbium YAG laser on vaginal lactobacilli, vaginal pH and vaginal atrophy symptoms. This study reports the objective and subjective measurements of vaginal atrophy after vaginal erbium YAG laser treatment. The results show an increase of vaginal lactobacilli grading after two laser applications. The increase of vaginal lactobacilli grading can be described by the effect of vaginal laser on vaginal epithelial maturation that superficial cells of vaginal epithelium are increased after treatment with vaginal laser. The superficial cells are glycogen-rich cells and lactobacilli use glycogen as their nutrients and produce lactic acid. Moreover, vaginal atrophy symptoms assessed by visual analog scale (VAS) and vaginal atrophy score were improved after laser treatments. The reduction in VAS score in this study is similar to the results of previous studies. 5–8,13−15 However, unlike several reports, 9 , 16 this study does not revealed statistically difference of vaginal pH before and after vaginal laser applications. This can be resulted from the majority of participants with grade 1 vaginal lactobacilli after vaginal laser treatment. Their vaginal epithelium contains only few lactobacilli that cannot produce enough lactic acid to lower vaginal pH. The safety of intravaginal laser therapy is one of major concerns. The result form previous studies showed only few minor adverse events after vaginal laser applications. 5 , 8 , 16 , 17 In our study, there was only one patient in sham group complained about pain after treatment and it was improved during the follow-up period. While there was no reported side effect after treatment in laser group. Therefore, the safety result form our study is concordant with previous studies 5 , 8 and can confirm the short-term safety of vaginal erbium YAG laser treatment. However, long term follow-up is needed to evaluate the long-term safety of this treatment. There are several strengths in this study. First, this study is a randomized sham-controlled study which can diminish the bias and placebo effect. Second, our study evaluates both subjective outcome (VAS score) and objective outcomes (vaginal lactobacilli, vaginal pH, vaginal atrophy score) of vaginal atrophy after vaginal laser treatment. The limitation of this study is different baseline characteristic between laser group and sham group (participants in laser group were younger that participants in sham group) which is resulted from imperfect randomization. There was significant amount of participants loss to follow-up during study period because of COVID-19 situation and personal illness that did not related to the procedure. However, the amount of participants loss to follow-up were similar in both laser group and sham group (2/22 and 3/22, respectively). Therefore, an effect of loss to follow-up might not interfere with the outcome of this study. For further research, increases sample size or vaginal laser applications might show statistically improvement of both subjective and objective measurements of vaginal atrophy after vaginal erbium laser. Conclusion There was no statistically significant difference of vaginal lactobacilli grading before and after treatment with erbium YAG laser as compared to sham procedure. However, grade of lactobacilli tends to increase after two applications of vaginal laser. Vaginal “dryness” symptom was improved significantly after treatment with erbium YAG laser. There was no reported serious adverse event. Declarations Ethics approval and consent to participate: this study had been performed in accordance with the Declaration of Helsinki and was approved by Institutional Review Board of Faculty of Medicine, Chulalongkorn University Consent for publication: Not applicable Availability of data and materials: all data and materials are described in the manuscript and tables Competing interests: the authors declare that they have no competing interests Funding: the study was funded by the Ratchadapisek Sompoch Endowment Fund Chulalongkorn University Fund. Authors' contributions: N.P. wrote the main manuscript text, prepared all figures and tables, K.P and A.S. reviewed the manuscript Acknowledgements: we would like to thank the Gynecologic Outpatient Clinic and Gender Health Clinic at King Chulalongkorn Memorial Hospital for their support in collecting the data. Special thanks to Dr.Tanittha Chatsuwan, Department of Microbiology, Faculty of Medicine, Chulalongkorn University and her colleagues who evaluated the grade of vaginal lactobacilli. Of course, we are grateful to all subjects in this study. References Berek J, Novak D. Berek & Novak's gynecology. 16th ed. Philadelphia: Wolters Kluwer; 2020. Chapter 18, Menopause;435. Portman DJ, Gass MLS. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the international society for the study of women’s sexual health and the North American menopause society. Climacteric. 2014;17(5):557–63. Stephanie S, Richa S, Ekta K. Genitourinary syndrome of menopause: management strategies for the clinician. Mayo Clin Proc. 2017;92(12):1842–9. Walter JE, Larochelle A. No. 358-Intravaginal laser for genitourinary syndrome of menopause and stress urinary incontinence. J Obstet Gynaecol Can. 2018;40(4):503–11. Pitsouni E, Grigoriadis T, Falagas ME, Salvatore S, Athanasiou S. Laser therapy for the genitourinary syndrome of menopause. a systematic review and meta-analysis. Maturitas. 2017;103(9):78–88. Gaspar A, Brandy H, Gomez V, Luque D. Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause. Laser Surg Med. 2017;49(2):160–8. Gambacciani M, Levacini M, Cervigni M. Vaginal erbium laser: the second-generation thermotherapy for the genitourinary syndrome of menopause. Climacteric. 2015;18(5):757–63. Gambacciani M, Levacini M, Russo E, Vacca L, Simoncini T, Cervigni M. Long-term effects of vaginal erbium laser in the treatment of genitourinary syndrome of menopause. Climacteric. 2018;21(2):148–52. Athanasiou S, Pitsouni E, Antonopoulou S, Zacharakis D, Salvatore S, Falagas ME. The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women. Climacteric. 2016;19(5):512–8. Amabebe E, Anumba DOC. The vaginal microenvironment: the physiologic role of lactobacilli. Front Med. 2018;13(5):181. Gambacciani M, Palacios S. Laser therapy for the restoration of vaginal function. Maturitas. 2017;99(5):10–5. Redondo-Lopez V, Cook RL, Sobel JD. Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev Infect Dis. 1990;12(5):856–72. Hutchinson-Colas J, Segal S. Genitourinary syndrome of menopause and the use of laser therapy. Maturitas. 2015;82(4):342–5. Rabley A, O'Shea T, Terry R, Byun S, Moy ML. Laser therapy for genitourinary syndrome of menopause. Curr Urol Rep. 2018;19(10):83. Jha S, Wyld L, Krishnaswamy PH. The impact of vaginal laser treatment for genitourinary syndrome of menopause in breast cancer survivors: a systematic review and meta-analysis. Clin Breast Cancer. 2019;19(4):556–62. Mothes AR, Runnebaum M, Runnebaum IB. Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment. J Cancer Res Clin Onco . 2018;144(5):955–60. Gambacciani M, Elia D, Berreni N, Bohbot JM, Druckmann R, Geoffrion H, et al. Genitourinary syndrome of menopause (GSM) and laser VEL: a review. Horm Mol Biol Clin Investig. 2020;41(1):307–11. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Sep, 2023 Read the published version in BMC Women's Health → Version 1 posted Editorial decision: Major revision 22 Nov, 2022 Reviews received at journal 18 Nov, 2022 Reviewers agreed at journal 15 Nov, 2022 Reviewers agreed at journal 05 Nov, 2022 Reviewers agreed at journal 05 Nov, 2022 Reviewers invited by journal 05 Nov, 2022 Editor assigned by journal 05 Nov, 2022 Editor invited by journal 16 Oct, 2022 Submission checks completed at journal 16 Oct, 2022 First submitted to journal 03 Oct, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2128372","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":144551717,"identity":"a9821c97-fc9e-4bff-ba80-320c887f0043","order_by":0,"name":"Nuttanun Panyawongudom","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nuttanun","middleName":"","lastName":"Panyawongudom","suffix":""},{"id":144551720,"identity":"b6b09fee-9568-40ce-bf0d-68c630518c48","order_by":1,"name":"Krasean Panyakhamlerd","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYBACCSgtZwCmDCyI12JswMAM0iKBTzGqlsQNYC0MRGiRnH348YcPNXfSt7P3H93wo0CCgb+9OwGvFmm+NDPJGcee5e7sOcx2swfoMIkzZzfg1SLHw2DGzMN2OHfDjWS2GzxALQYSuYS0sH/+/Off4XQDoJabf4jRIs3DYyDN2HY4AaTlNlG2SPbwlEn29h023HDmsNltGQMJHoJ+kTjDvvnDj2+H5Q2ONz67+eaPjRx/ey9+LRiAhzTlo2AUjIJRMAqwAgCHJkToS/l4PwAAAABJRU5ErkJggg==","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Krasean","middleName":"","lastName":"Panyakhamlerd","suffix":""},{"id":144551721,"identity":"23608b97-3b9f-4b2c-865b-ea0d2b802e02","order_by":2,"name":"Ammarin Suwan","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ammarin","middleName":"","lastName":"Suwan","suffix":""}],"badges":[],"createdAt":"2022-10-03 12:44:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2128372/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2128372/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12905-023-02590-y","type":"published","date":"2023-09-26T15:01:35+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":27941039,"identity":"95d55584-1b13-4247-893d-b0188d285617","added_by":"auto","created_at":"2022-10-18 15:55:35","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29683,"visible":true,"origin":"","legend":"\u003cp\u003eConsort diagram shows the recruitment and drop out of the participants in lasergroup and sham group\u003c/p\u003e","description":"","filename":"groupimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-2128372/v1/14292ad64445501be3a787ff.jpeg"},{"id":43974507,"identity":"c40052d1-3163-4048-acd5-ce187ab68127","added_by":"auto","created_at":"2023-10-02 15:08:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":326971,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2128372/v1/94839a77-38cc-4e9d-a84f-b0e9ba7f722a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Number of vaginal lactobacilli in postmenopausal women with vaginal atrophy before and after treatment with erbium YAG laser, a randomized sham-controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVaginal atrophy or genitourinary syndrome of menopause is commonly found in postmenopausal women. As many as 50% of postmenopausal women suffered from vaginal atrophy symptoms.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e This condition is caused by low estrogen level after menopause.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The diagnosis of vaginal atrophy is clinical diagnosis which are vaginal dryness, irritation, pain, dyspareunia and urinary symptoms.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTreatments of vaginal atrophy can be either local hormonal treatment or non-hormonal treatments. Currently, vaginal estrogen therapy is one of the standard treatments of vaginal atrophy. However, caution was suggested in hormone sensitive cancer survivors.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Moreover, number of patients denied hormonal treatment. This leads to choices of non-hormonal treatments including vaginal erbium YAG laser.\u003c/p\u003e \u003cp\u003eVaginal laser is a novel treatment for vaginal atrophy. There are two types of laser used for intravaginal therapy \u0026ndash; CO\u003csub\u003e2\u003c/sub\u003e and erbium YAG laser.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e The advantage of erbium YAG laser is that it has 15 times more water absorption than CO\u003csub\u003e2\u003c/sub\u003e laser causing less penetration, faster tissue healing phase, fewer side effects and lesser pain compared with CO\u003csub\u003e2\u003c/sub\u003e laser.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe effect of vaginal laser is thermal effect to vaginal epithelium resulting in an expression of heat-shock proteins which stimulate growth factors activities, neovascularization, neocollagenesis, extracellular matrix formation and increase vaginal thickness and elasticity. However, thermal effect of erbium YAG laser is less than that of CO\u003csub\u003e2\u003c/sub\u003e laser causing no tissue damage.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMany prospective studies reported that vaginal erbium YAG laser can improve vaginal atrophy symptoms and its effect can be compared with vaginal estrogen therapy.\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e A systematic review and meta-analysis of laser therapy for genitourinary syndrome of menopause publish in 2017, included 14 studies of both CO\u003csub\u003e2\u003c/sub\u003e and erbium YAG laser, showed that vaginal laser improved all genitourinary syndrome of menopause (GSM) symptoms, female sexual function index (FSFI), vaginal health index score (VHIS) and vaginal maturation value (VMV). However, the quality of evidences was \u0026ldquo;low\u0026rdquo; or \u0026ldquo;very low\u0026rdquo; because there was no randomized sham-controlled study that can decrease the bias and placebo effect.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eVaginal lactobacilli are normal vaginal flora that can produce antimicrobial compounds such as hydrogen peroxide and lactic acid, and compete with pathogens for vaginal adherence.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Number of vaginal lactobacilli increases after vaginal epithelial maturation because of an increase of glycogen storage in superficial vaginal epithelium.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Therefore, it can be used as an objective measurement of vaginal atrophy. A prospective study of vaginal CO\u003csub\u003e2\u003c/sub\u003e laser and vaginal flora reported a significant increase of vaginal lactobacilli and a significant decease of vaginal pH after 3 applications of CO\u003csub\u003e2\u003c/sub\u003e laser.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e However, there was no study to date about the effect of vaginal erbium YAG laser and number of vaginal lactobacilli.\u003c/p\u003e \u003cp\u003eThis study aimed to measure the effect of vaginal erbium YAG laser on number of vaginal lactobacilli. Besides, we also evaluate vaginal pH, vaginal atrophy symptoms and adverse effects after vaginal erbium YAG laser treatment.\u003c/p\u003e"},{"header":"Material And Methods","content":"\u003cp\u003eThis randomized sham-controlled study was conducted at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand, between May 2019 and September 2020. The target population were postmenopausal women attending gynecology clinic or gender health clinic with vaginal atrophy symptoms (dryness, dyspareunia, irritation, pain). Inclusion criteria were postmenopausal women with at least one symptom of moderate to severe vaginal atrophy and age more than 40 years. (Moderate to severe vaginal atrophy was defined by the most bothersome symptom score at least \u0026ldquo;2\u0026rdquo; in at least one vaginal atrophy symptoms (0\u0026thinsp;=\u0026thinsp;no symptom, 1\u0026thinsp;=\u0026thinsp;mild, 2\u0026thinsp;=\u0026thinsp;moderate, 3\u0026thinsp;=\u0026thinsp;severe). Exclusion criteria were history of hormonal therapy, vaginal lubricants, vaginal moisturizers or spermicide in previous 3 months, active or recent genitourinary tract infection in previous 1-month, abnormal vaginal bleeding, genital organ prolapse stage at least II, history of vaginal surgery in previous 3 months and previous vaginal laser treatment.\u003c/p\u003e \u003cp\u003eFor sample size calculation, two independent proportions formula was used. The sample size was calculated using data from our pilot study. The proportion in study group and control group were 0.4 and 0.9 respectively. (Outcome for sample size calculation was proportion of participants with grade 1 vaginal lactobacilli after vaginal erbium laser treatment and after sham operation) Using 5% type I error and 20% type II error, the calculated sample size was 17 per group. Adding 20% drop out, total of 42 participants were needed.\u003c/p\u003e \u003cp\u003e After completed written informed consent, all participants were interviewed to collect demographic data and randomized into laser group and sham group using block of four randomization with sealed enveloped. Participants in laser group were treated with erbium in yttrium aluminum-garnet crystal (Er:YAG) laser (Fotona Smooth\u0026trade; XS, Fotona, Ljubljana, Slovenia), wavelength of 2940 nm, spot size 7 mm, frequency 1.6 Hz, laser energy 6.0 J/cm2 2 applications every 4 weeks. Participants in sham group were treated with 2 sham operations every 4 weeks. Sham operation was done while patient was in lithotomy position and placed an exactly the same equipment of vaginal erbium laser, but there was no laser energy from the equipment. A duration of sham operation was equal to that of vaginal erbium laser treatment or about 5 minutes. All participants were appointed for follow-up visit 4 weeks after the second laser or sham application. Vaginal atrophy symptoms were measured by visual analog scale (VAS) in every visit. Vaginal swabs were collected from posterior fornix and vaginal pH was measured using pH indicator strip applied to lateral vaginal wall. Vaginal atrophy score, as shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, was assessed in every visit. The vaginal swabs were sent to a microbiologist to evaluate the vaginal lactobacilli grading. Vaginal lactobacilli were reported into 4 grades according to number of lactobacilli per high power field. (grade 1: \u0026lt; 6/HPF, grade 2: 6\u0026ndash;20/HPF, grade 3: 21\u0026ndash;50/HPF, grade 4: \u0026gt; 50/HPF) All participants were blinded during the study period. All vaginal swab slides were sent to a microbiologist with identification numbers that did not mention about study group. Therefore, a microbiologist who evaluated vaginal lactobacilli grading was also blinded.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssessment of vaginal atrophy score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot present (0)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild (1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate (2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSevere (3)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDryness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal lubrication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSlightly decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMinimal lubrication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDry\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRugae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal number and depth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReduced rugae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRare rugae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSmooth vagina\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePallor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal pink\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLight pink\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVery pale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eWhite/deep red\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePetechiae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBleeds on scraping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBleeds on contact\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClearly seen\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucosal elasticity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003edecreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStenosis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e This study was funded by Ratchadapisek Sompot fund and was approved by Institutional Review Board of Faculty of Medicine, Chulalongkorn University. Statistical analysis was performed by SPSS version 22.0. For descriptive statistic, Number, percentage and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) was used for continuous data while number and percent were used for categorical data. For analytical statistic, ANOVA repeated measures and Friedman test were used for continuous and categorial data, respectively. An overall statistical significance was considered when the \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e Total 44 participants were recruited and randomized to 22 in laser group and 22 in sham group. As 5 of them were lost to follow-up, total 39 participants were completed (the detail was shown by consort diagram in flow chart 1). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows similar baseline characteristics of participants in laser group and sham group except for \u0026ldquo;age\u0026rdquo; that participants in laser group were younger than those in sham group (mean age in sham group was 60.4, mean age in laser group was 55.5). There was no significant difference in parity, menopausal age, year since menopause, baseline vaginal atrophy symptoms measured by VAS, baseline vaginal pH and baseline vaginal atrophy score between participants in both groups. There was no significant difference of BMI between two groups. There were similar baseline vaginal lactobacilli between laser group and sham group. The most presenting symptom of participants was dyspareunia (54.5% in both groups).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of the subjects in laser group and sham group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLaser group (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSham group (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eParity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMenopausal age (year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eYear since menopause (year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal atrophy symptoms (VAS)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal pH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal atrophy score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLaser group N(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSham group N(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18.5-24.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(54.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(59.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25-29.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(31.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLactobacilli grade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMost symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDryness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(36.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(18.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspareunia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(54.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrritation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(22.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(4.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows vaginal lactobacilli grading in each visit of both groups. Visit 1 is pre-treatment. Visit 2 and 3 are after 1st and 2nd treatment respectively. In the laser group, grade of vaginal lactobacilli was higher significantly after 2nd treatment (p\u0026thinsp;=\u0026thinsp;0.02). However, there was no statistically significant change of vaginal lactobacilli after 2 sham procedures. To compare between groups, using logistic regression for calculation of odd ratio (OR) of improvement after 2 laser treatment, adjusted OR for age was 5.32 (95%CI\u0026thinsp;=\u0026thinsp;0.5\u0026ndash;56.21, p\u0026thinsp;=\u0026thinsp;0.17). Therefore, compared with sham group, the improvement of vaginal lactobacilli grading of participants in laser group was not reach statistically significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVaginal lactobacilli grading, vaginal atrophy symptoms (VAS), vaginal atrophy score, vaginal pH in each visit of participants in laser group and sham group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eLaser group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eSham group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLactobacilli grade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGrade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGrade 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGrade 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGrade 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGrade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eGrade 4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal atrophy symptoms (VAS)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eLaser group (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eSham group (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e16.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e13.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal atrophy score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVaginal pH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisit 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVaginal atrophy symptoms, which were measured by visual analog scale (VAS), were significantly decreased after treatment in laser group. However, there was not statistically difference of vaginal atrophy symptoms after sham operations. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e also demonstrates that vaginal atrophy score after treatment were significantly lowered in both laser group and sham group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no statistically significant difference of vaginal pH before and after treatment in both groups (p\u0026thinsp;=\u0026thinsp;0.20 and 0.15 in laser group and sham group, respectively).\u003c/p\u003e \u003cp\u003eTo determine secondary outcomes, mixed effect multiple linear regression was used and showed that there was significant change in vaginal dryness (mean change = -2.28, p\u0026thinsp;=\u0026thinsp;0.01) and vaginal atrophy score (mean change = -1.49, p\u0026thinsp;=\u0026thinsp;0.03) before and after treatment in laser group as compared to sham group. The changes of vaginal pH, total vaginal atrophy symptoms, pain, irritation and dyspareunia were not reach statistically significant. The secondary outcome results are shown in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. For the adverse event, only one participant in sham group complained about pain during operation but it was improved after the operation.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSecondary outcome adjusted with time and age due to imperfect randomization\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-6.44 to 0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDryness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4.11 to -0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrritation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.64 to 0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSoreness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.44 to 0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspareunia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.22 to 0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal atrophy score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.82 to -0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.61 to 0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eVaginal erbium YAG laser is a novel treatment for vaginal atrophy or, newly termed, genitourinary syndrome of menopause (GSM). The literatures showed effectiveness and safety of intravaginal laser therapy while erbium YAG laser is considered as the safer choice as compared to fractional CO\u003csub\u003e2\u003c/sub\u003e laser because of its non-ablative effect.\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMechanism of action of erbium YAG laser is photothermal effect to vaginal epithelium causes superficial tissue shrinkage, neovascularization, neocollagenesis results in vaginal tissue thickening and increases vaginal elasticity.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn the literature, there are few studies reporting an improvement of vaginal atrophy symptoms after vaginal erbium YAG laser treatment.\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e However, there was no study about vaginal erbium YAG laser and vaginal lactobacilli which can be used as an objective measurement. Vaginal lactobacilli are vaginal normal flora that dynamically changed with vaginal maturation and play a role in maintaining vaginal acidity and compete with pathogens.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo our knowledge, this study is the first randomized sham-controlled study to assess the effect of vaginal erbium YAG laser on vaginal lactobacilli, vaginal pH and vaginal atrophy symptoms. This study reports the objective and subjective measurements of vaginal atrophy after vaginal erbium YAG laser treatment. The results show an increase of vaginal lactobacilli grading after two laser applications. The increase of vaginal lactobacilli grading can be described by the effect of vaginal laser on vaginal epithelial maturation that superficial cells of vaginal epithelium are increased after treatment with vaginal laser. The superficial cells are glycogen-rich cells and lactobacilli use glycogen as their nutrients and produce lactic acid. Moreover, vaginal atrophy symptoms assessed by visual analog scale (VAS) and vaginal atrophy score were improved after laser treatments. The reduction in VAS score in this study is similar to the results of previous studies.\u003csup\u003e5\u0026ndash;8,13\u0026minus;15\u003c/sup\u003e However, unlike several reports,\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e this study does not revealed statistically difference of vaginal pH before and after vaginal laser applications. This can be resulted from the majority of participants with grade 1 vaginal lactobacilli after vaginal laser treatment. Their vaginal epithelium contains only few lactobacilli that cannot produce enough lactic acid to lower vaginal pH.\u003c/p\u003e \u003cp\u003eThe safety of intravaginal laser therapy is one of major concerns. The result form previous studies showed only few minor adverse events after vaginal laser applications.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e In our study, there was only one patient in sham group complained about pain after treatment and it was improved during the follow-up period. While there was no reported side effect after treatment in laser group. Therefore, the safety result form our study is concordant with previous studies\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e and can confirm the short-term safety of vaginal erbium YAG laser treatment. However, long term follow-up is needed to evaluate the long-term safety of this treatment.\u003c/p\u003e \u003cp\u003eThere are several strengths in this study. First, this study is a randomized sham-controlled study which can diminish the bias and placebo effect. Second, our study evaluates both subjective outcome (VAS score) and objective outcomes (vaginal lactobacilli, vaginal pH, vaginal atrophy score) of vaginal atrophy after vaginal laser treatment.\u003c/p\u003e \u003cp\u003eThe limitation of this study is different baseline characteristic between laser group and sham group (participants in laser group were younger that participants in sham group) which is resulted from imperfect randomization.\u003c/p\u003e \u003cp\u003eThere was significant amount of participants loss to follow-up during study period because of COVID-19 situation and personal illness that did not related to the procedure. However, the amount of participants loss to follow-up were similar in both laser group and sham group (2/22 and 3/22, respectively). Therefore, an effect of loss to follow-up might not interfere with the outcome of this study.\u003c/p\u003e \u003cp\u003eFor further research, increases sample size or vaginal laser applications might show statistically improvement of both subjective and objective measurements of vaginal atrophy after vaginal erbium laser.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThere was no statistically significant difference of vaginal lactobacilli grading before and after treatment with erbium YAG laser as compared to sham procedure. However, grade of lactobacilli tends to increase after two applications of vaginal laser. Vaginal \u0026ldquo;dryness\u0026rdquo; symptom was improved significantly after treatment with erbium YAG laser. There was no reported serious adverse event.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cli\u003eEthics approval and consent to participate: this study had been performed in accordance with the Declaration of Helsinki and was approved by\u0026nbsp;Institutional Review Board of Faculty of Medicine, Chulalongkorn University\u003c/li\u003e\n \u003cli\u003eConsent for publication: Not applicable\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials: all data and materials are described in the manuscript and tables\u003c/li\u003e\n \u003cli\u003eCompeting interests:\u0026nbsp;the authors declare that they have no competing interests\u003c/li\u003e\n \u003cli\u003eFunding:\u0026nbsp;the study was funded by the Ratchadapisek Sompoch\u0026nbsp;Endowment Fund Chulalongkorn University Fund.\u003c/li\u003e\n \u003cli\u003eAuthors\u0026apos; contributions:\u0026nbsp;N.P. wrote the main manuscript text, prepared all figures and tables, K.P and A.S. reviewed the manuscript\u003c/li\u003e\n \u003cli\u003eAcknowledgements:\u0026nbsp;we would like to thank the Gynecologic Outpatient Clinic and\u0026nbsp;Gender Health\u0026nbsp;Clinic at King Chulalongkorn Memorial Hospital for their support in collecting the data. \u0026nbsp;Special thanks to\u0026nbsp;Dr.Tanittha Chatsuwan,\u0026nbsp;Department of Microbiology, Faculty of Medicine, Chulalongkorn University\u0026nbsp;and her\u0026nbsp;colleagues\u0026nbsp;who evaluated the grade of vaginal lactobacilli.\u0026nbsp;Of course, we are grateful to all subjects in this study.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBerek J, Novak D. Berek \u0026amp; Novak's gynecology. 16th ed. Philadelphia: Wolters Kluwer; 2020. Chapter 18, Menopause;435.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePortman DJ, Gass MLS. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the international society for the study of women\u0026rsquo;s sexual health and the North American menopause society. Climacteric. 2014;17(5):557\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStephanie S, Richa S, Ekta K. Genitourinary syndrome of menopause: management strategies for the clinician. Mayo Clin Proc. 2017;92(12):1842\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalter JE, Larochelle A. No. 358-Intravaginal laser for genitourinary syndrome of menopause and stress urinary incontinence. J Obstet Gynaecol Can. 2018;40(4):503\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePitsouni E, Grigoriadis T, Falagas ME, Salvatore S, Athanasiou S. Laser therapy for the genitourinary syndrome of menopause. a systematic review and meta-analysis. Maturitas. 2017;103(9):78\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaspar A, Brandy H, Gomez V, Luque D. Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause. Laser Surg Med. 2017;49(2):160\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGambacciani M, Levacini M, Cervigni M. Vaginal erbium laser: the second-generation thermotherapy for the genitourinary syndrome of menopause. Climacteric. 2015;18(5):757\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGambacciani M, Levacini M, Russo E, Vacca L, Simoncini T, Cervigni M. Long-term effects of vaginal erbium laser in the treatment of genitourinary syndrome of menopause. Climacteric. 2018;21(2):148\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAthanasiou S, Pitsouni E, Antonopoulou S, Zacharakis D, Salvatore S, Falagas ME. The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women. Climacteric. 2016;19(5):512\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmabebe E, Anumba DOC. The vaginal microenvironment: the physiologic role of lactobacilli. Front Med. 2018;13(5):181.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGambacciani M, Palacios S. Laser therapy for the restoration of vaginal function. Maturitas. 2017;99(5):10\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRedondo-Lopez V, Cook RL, Sobel JD. Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev Infect Dis. 1990;12(5):856\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHutchinson-Colas J, Segal S. Genitourinary syndrome of menopause and the use of laser therapy. Maturitas. 2015;82(4):342\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRabley A, O'Shea T, Terry R, Byun S, Moy ML. Laser therapy for genitourinary syndrome of menopause. Curr Urol Rep. 2018;19(10):83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJha S, Wyld L, Krishnaswamy PH. The impact of vaginal laser treatment for genitourinary syndrome of menopause in breast cancer survivors: a systematic review and meta-analysis. Clin Breast Cancer. 2019;19(4):556\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMothes AR, Runnebaum M, Runnebaum IB. Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment. J Cancer Res Clin \u003cem\u003eOnco\u003c/em\u003e. 2018;144(5):955\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGambacciani M, Elia D, Berreni N, Bohbot JM, Druckmann R, Geoffrion H, et al. Genitourinary syndrome of menopause (GSM) and laser VEL: a review. Horm Mol Biol Clin Investig. 2020;41(1):307\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Erbium YAG laser, Vaginal lactobacilli, Randomized sham-controlled trial, Menopause, Vaginal atrophy, Vaginal pH","lastPublishedDoi":"10.21203/rs.3.rs-2128372/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2128372/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePrimary objective: \u003c/strong\u003eTo evaluate the effect of erbium YAG laser on the number of vaginal lactobacilli in postmenopausal women.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary objectives:\u003c/strong\u003e To evaluate the effects of erbium YAG laser on vaginal atrophy symptoms and vaginal pH in postmenopausal women.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods: \u003c/strong\u003eA total of 44 postmenopausal women meeting inclusion criteria were randomized in laser group (n=22) and sham group (n=22). Vaginal lactobacilli grading, vaginal pH, vaginal atrophy score and vaginal atrophy symptoms (dryness, irritation, soreness, dyspareunia) wereassessed before and after treatment with erbium YAG laser for 2 consecutive times, 4 weeks interval; the results were compared with the effects of sham procedure. Any adverse events after the treatment were recorded. Statistical analysis was performed by using SPSS program and p \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 44women were included and 5were lost to follow-up. Compared with sham procedure, there was an improvement of vaginal lactobacilli grading in laser group (5/20 in laser group and 1/19 in sham group). However, the improvement did not reach statistically significant (adjusted OR = 5.32, 95%CI = 0.5-56.21). Vaginal atrophy symptoms measured by VAS and vaginal pH were improved in both groups without statistically significant difference between groups. Vaginal “dryness” VAS and vaginal atrophy score after treatment were significantly lowered in laser group compared to sham group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e This study showed an improvement in vaginal lactobacilli grading after vaginal laser treatment. However, the difference of vaginal lactobacilli grading after treatment in both groups did not reach statistically significant.\u003c/p\u003e","manuscriptTitle":"Number of vaginal lactobacilli in postmenopausal women with vaginal atrophy before and after treatment with erbium YAG laser, a randomized sham-controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-10-18 15:55:33","doi":"10.21203/rs.3.rs-2128372/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-11-22T15:22:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-11-18T21:10:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55a18840-1c74-4762-a4d3-69a0058021ef","date":"2022-11-15T16:22:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d5e6e1f4-9323-4b62-a3c6-17a63ce82937_SNPRID","date":"2022-11-05T07:02:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209ff2ad-9fee-4f7c-9c5f-ee7f4839183a","date":"2022-11-05T07:02:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-11-05T06:42:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-11-05T06:40:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-10-16T07:45:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-10-16T07:41:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2022-10-03T12:36:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fbed42da-bf7f-4845-8f70-37f2be0c4786","owner":[],"postedDate":"October 18th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-02T15:04:17+00:00","versionOfRecord":{"articleIdentity":"rs-2128372","link":"https://doi.org/10.1186/s12905-023-02590-y","journal":{"identity":"bmc-womens-health","isVorOnly":false,"title":"BMC Women's Health"},"publishedOn":"2023-09-26 15:01:35","publishedOnDateReadable":"September 26th, 2023"},"versionCreatedAt":"2022-10-18 15:55:33","video":"","vorDoi":"10.1186/s12905-023-02590-y","vorDoiUrl":"https://doi.org/10.1186/s12905-023-02590-y","workflowStages":[]},"version":"v1","identity":"rs-2128372","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2128372","identity":"rs-2128372","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}