Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Syndrome

Menopause

All Drugs and Chemicals

Aromatase Inhibitors

1. Power: 30 W.
2. Dwell time: 1000 μs.
3. Spacing: 1000 μm.
4. Depth: SmartStack parameter from 1 to 3 depending on the treatment status.
5. D-pulse mode.
6. At the introitus the power will be reduced to 24 W

1. Phase I (vaginal) Renovalase™ mode with (a) fluence of 5,5J/cm2, (b) SMOOTHTM mode frequency 1.6 Hz, and (c) spot size 7 mm.
2. Phase II (vestibulum and introitus) Renovalase™ mode with (a) fluence 10 J/cm2, (b) SMOOTHTM mode frequency 1.6Hz, and (c) spot size 7 mm.

1. The blocking device is inserted over the laser outlet before attaching the application speculum. With this device the laser beam is blocked entirely.
2. Phase I (vaginal) Renovalase™ mode with (a) fluence of 5,5J/cm2, (b) SMOOTHTM mode frequency 1.6 Hz, and (c) spot size 7 mm.
3. Phase II (vestibulum and introitus) Renovalase™ mode with (a) fluence 1,5 J/cm2, (b) SMOOTHTM mode frequency 1.6Hz, and (c) spot size 7 mm.

intravaginal laser

Susanne Housmans, MD

Jan Deprest, PhD

To study the efficacy and safety of intravaginal CO2 laser versus intravaginal Er:YAG laser and sham application in alleviating genitourinary symptoms in patients receiving an aromatase inhibitor as adjuvant treatment of breast cancer

The objective is to compare microablative fractional CO2 laser (CO2 laser) (SmartXide2 V2 LR, Monalisa Touch; DEKA, Florence, Italy) and non-ablative photothermal Erbium:YAG laser (Er:YAG laser) (Fotona Smooth™ XS; Fotona, Ljubljana, Slovenia) - with sham vaginal applications for treatment of vaginal dryness as the leading symptom in breast cancer patients with iatrogenic menopause and treated with an AI.

3 parallel arms of equal size, participants can cross over after 3 initial treatments

participant and outcome assessor are blinded

Use of Fractional CO2 Laser Versus Erbium:YAG Laser for the Treatment of GSM in Patients Using Aromatase Inhibitors

Use of Fractional CO2 Laser Versus Erbium:YAG Laser for the Treatment of Genitourinary Syndrome of Menopause (GSM) in Patients Using Aromatase Inhibitors: Double Blinded Randomized Controlled Clinical Trial.

measured with FSFI questionnaire. The cut-off score of \>26,55 will be used to discriminate between women with impaired and unimpaired sexual functioning

Determined by questioning the need the participant feels for repeat treatment, and its nature (repeat laser or alternatives) until two years after the end of treatment.

Measured with a pH indicator strip (range 3.6-6.1) and is sampled from the lateral vaginal wall in the lower third of the vagina

Scoring of vaginal moisture, vaginal fluid volume, vaginal elasticity, vaginal pH, and vaginal epithelial integrity on a scale of 1 (poorest) to 5 (best) according to the methods of Robert Wood Johnson Medical School. The lower the score, the greater the atrophy. Vaginal moisture is an assessment of the appearance and spread or consistency of the secretions which coat the vagina. Vaginal elasticity is a measure of the ability of the vaginal tissue to stretch from the examiner's finger. Vaginal epithelial integrity takes into account color, thickness, and ability of the tissue to resist breaking secondary to touch.

A vaginal smear will be obtained from the lateral vaginal wall using a spatula and will be stained according to the Papanicolaou technique. The Vaginal Maturation Index (VMI) is evaluated by defining the proportion of superficial, intermediate, and parabasal epithelial cells on the smear. To combine this information into a single score for quantifying estrogenization, the VMV was calculated. It is based on weighted proportions of cell types from the VMI and calculated using Meisels' formula: the percentage of superficial cells (S) plus 0.5 times the percentage of intermediate cells (I) coded from the cytology sample \[MV= %S + (0.5 × % I)

Adverse events are questioned at each visit following an intravaginal treatment.

Universitaire Ziekenhuizen KU Leuven

Breast Diseases

Skin Diseases

Central Nervous System Depressants

Estrogens, Conjugated (USP)

Anesthetics

Estrogens

During our study, women will undergo treatment intravaginally and vulvar with the fractional microablative CO2 laser system (SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy). A treatment cycle includes three laser applications (every 40-50 days, approximately 6 weeks). The procedure will be performed in the outpatient clinic and does not require any specific preparation (e.g. analgesia/anesthesia).

The women in the vaginal estrogen group will be prescribed and asked to administer: Conjugated estrogen cream (Premarin®): 0.5 g of cream intravaginally daily (using applicator or fingertip) for two weeks (fourteen days) then 0.5 g twice weekly for 24 ± 2 additional weeks.

Microablative Fractional CO2 Vaginal Laser Therapy

Microablative Fractional CO2 Laser Therapy

The purpose of this study is to assess the efficacy of a fractional CO2 laser ("SmartXide2 - V2LR", DEKA M.E.L.A., Florence - Italy) "the Laser" in the treatment of genitourinary symptoms of menopause, female sexual function, and urogenital health in comparison to vaginal estrogen. Only breast cancer patients who have HR (-) breast cancer are planning to be included in the vaginal estrogen group.

The investigators aim to determine the efficacy of the MonaLisaTouch Laser in comparison with vaginal estrogen in the management and treatment of GSM symptoms resulting in vaginal atrophy, sexual dysfunction and a decreased quality of life in women with a history of breast cancer. Patients will be stratified according to menopausal status prior to breast cancer therapy and HR tumor status. Fractional CO2 laser therapy has been approved by Health Canada for use in menopausal women with GSM, nevertheless long term efficacy and safety data is lacking in the breast cancer survivor population. In the short term (i.e. 6 month follow up), research has shown that this therapy is a safe and effective treatment that has promising benefits with little to no reported adverse events.

MonaLisa Laser Intervention for Post-Menopausal Breast Cancer Patients: A SHE CAN Study

Randomized Clinical Trial Comparing the MonaLisa Laser Versus Vaginal Estrogen in Post-Menopausal Breast Cancer Patients: a SHE CAN Non-inferiority Study

The aim of our research, is to assess the impact of the MonaLisa Touch Laser on the sexual health and quality of life of breast cancer survivors with GSM in comparison to vaginal estrogen.

To compare subjective improvement of vaginal dryness in breast cancer survivors, using the 10 cm visual analog scale (VAS) for GSM symptoms 6 months post-treatment between groups.

Mount Sinai Hospital, Canada

Principal Investigator

Group A: Arm using basal treatment and adding vaginal laser using double blind to adjust the treatment to zero potence.

Group B: Arm using basal treatment and adding vaginal laser using double blind to adjust the treatment to regular potence.

CO2 LASER

CO2 SHAM LASER

Immaculada Alonso Vargas

Background: Vulvovaginal health, directly linked to sexual health, is a key factor for female pleasure. BCS receiving AI are likely to present severe GSM and sexual complaints. Innovative options, as vaginal laser therapy, are emerging to treat GSM and sexual dysfunctions. Nowadays, data in BCS is scarce, moreover, few studies included patients receiving AI \[16\]. Different meta-analysis \[17-23\] found GSM \[24, 25\] and sexual function \[9, 10\] may improve significantly at short-term, however, the body of evidence is of low quality. Therefore, before recommendation of laser therapy for sexual complaints in BCS with GSM, there are unmet needs to be solved: efficacy and safety at long-term, biases related to patients' expectations and a detailed assessment of the complex underpinnings of sexuality.

Aims: To evaluate sexual and vaginal health in BCS receiving AI with GSM, before and after CO2 laser therapy compared to a sham-controlled group.

Methods: Prospective, randomized, double-blind controlled study with two parallel study arms: 1) Fractional CO2 laser therapy (5monthly sessions). 2) Sham laser therapy (5monthly sessions). After end-treatment, patients are followed up at 1 month and 6 months. BCS treated or undergoing AI with GSM and sexual function impairment, will be suitable. All patients will maintain first-line non-hormonal treatment and sexual assessment (PLISSIT Model) according with usual care. The primary outcome is improvement in sexual function (FSFI total score). As secondary outcomes: resumption sexual activity, sexual activity frequency, dyspareunia (VAS), female sexual dysfunction, sexual dimensions (FSFI), body image (S-BIS), quality of life (SF-12), vaginal pH acidification, maturation index and Vaginal Health Index of Gloria Backmann, adverse events, satisfaction (Likert scale) and adherence to treatment.

Expected impact: Emergent, non-invasive, laser therapy has significant benefit for BCS with AI, improving subjective and objective sexual and vaginal health outcomes and adding value to the usual care multidisciplinary approach.

BACKGROUND:

Sexuality is a central aspect of being human throughout life encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy and reproduction. Most of these aspects may be affected in breast cancer survivors (BCS). In a recent meta-analysis, focused on sexual function through Female Sexual Function Index (FSFI) among BCS, female sexual dysfunction prevalence was 73,4% (95 % CI 64-82.8 %, I2 = 96.8 %) and mean FSFI 19.28 (95 % CI 17.39-21.16, I2 = 97.6 %). Several modifiable risk factors for sexual dysfunction in BCS may be optimum targets for intervention: amelioration of vaginal discomfort and urinary incontinence, the benefits of breast conserving surgery on body image or the evaluation of relationship quality. Due to the multifaceted nature of the factors affecting sexuality in BCS, most authors encouraged the need for comprehensive assessment and for a multidisciplinary approach.

BC diagnosis and/or its treatments (surgery, chemoradiotherapy, hormonal therapy) may altered sexual health. Vulvovaginal health, directly linked to sexual health, is a key factor for female pleasure. Genitourinary syndrome of menopause (GSM) is caused by decline in estrogen at menopause, which may also appear or worsen after systemic cancer treatments as aromatase inhibitors (AI). GSM is associated with sexual symptoms (lack of lubrication, discomfort or pain, impaired function), genital symptoms (dryness, burning, irritation) and urinary symptoms (urgency, dysuria, recurrent urinary tract infections). BCS receiving AI are one of the groups most likely to present severe GSM and sexual complaints. A cross-sectional study on 129 BCS during the first 2 years of adjuvant AI therapy, found 3 out of 4 women were distressed about their sexual problems. Only 52% of women had been sexually active when endocrine therapy began, but 79% of that group developed new sexual problems.

The first line of treatment for GSM is non-hormonal therapy (regular sexual activity, moisturizers-lubricants, pelvic-floor relaxation techniques, dilators) although in many women these options will not adequately control symptoms. Hormonal therapies must be used with caution in women with estrogen-dependent cancers. So, alternative options are emerging for this subset of patients, such as vaginal laser therapy. Different studies provided short-term data on non-cancer patients that showed laser therapy was feasible, safe and improved objective and subjective GSM. Data regarding sexuality derived from secondary endpoints and suggested that laser therapy may improve sexual function, mainly decreasing sexual pain. To date, data on laser therapy in BCS is scarce, moreover, few studies included patients receiving ongoing AI. The CO2 laser was the most frequently used device. Different reviews and meta-analysis found GSM and sexual function may improve significantly at short-term, however, the body of evidence is of low quality. Therefore, before recommendation for the use of laser therapy for sexual complaints in BCS with GSM, there are unmet needs to be solved as efficacy and safety at long-term, biases related to patients' expectations of therapy and a detailed assessment of the complex underpinnings of sexuality.

AIMS:

To answer the unmet needs previously mentioned, the aim of the current study is to verify the outcomes of sexual and vaginal health in breast cancer women receiving AI, who were experiencing symptoms of GSM, before and after CO2 laser therapy compared to a sham-controlled group.

Specifically, we will compare the following subjective and objective measurements of sexual and vaginal health:

MAIN GOAL: Report an improvement in sexuality:

* Primary outcome: sexual function (FSFI total score)
* Secondary sexual outcomes: resumption sexual activity (sexually active vs non-sexually active), sexual activity frequency (nº sexual activity/week), dyspareunia (VAS), female sexual dysfunction (VAS sexual life distress), sexual dimensions: desire, arousal, lubrication, orgasm, satisfaction and pain (FSFI) and body image (S-BIS)

OTHER OBJECTIVES: Report an improvement on GSM symptoms (efficacy) and quality of life, feasibility and safety of laser therapy in BCS:

- Secondary non-sexual outcomes: quality of life (SF-12). Verify an acidification of the vaginal pH, an improvement in the maturation index and an improvement in the Gloria Backmann Index: Vaginal Health Index. To evaluate toxicity associated with vaginal laser therapy in this population (AEs and SAEs). To determine how many women with the defined patient eligibility will complete all treatments.

METHODS:

DESIGN: Prospective, randomized, double-blind controlled study with two parallel study arms: ARM I: Patients undergo fractional CO2 laser therapy at 5 times points 30 days apart. ARM II: Patients undergo sham laser therapy at 5 time points 30 days apart. After completion of the treatment, patients are followed up at 1 month and 6 months.

RANDOMIZATION PROCESS: A randomization list will be generated in multiple blocks of 2 and 1: 1 ratio with STATA version 15.1 or higher.

STUDY SUBJECTS: Patients treated or undergoing AI for BC in the Breast Cancer Unit of the Hospital Clínic and who present symptoms related to GSM that condition their sexual function and quality of life, despite receiving first-line non-hormonal treatment: regular sexual activity (such as mutual and self-touch masturbation, manual or vibrator stimulation, oral sex, sexual intercourse, massage and other forms of physical intimacy), moisturizers, lubricants, pelvic-floor relaxation techniques and/or dilators. Inclusion and exclusion criteria are summarized in Table 1.

STUDY GROUPS: All patients will receive instructions to maintain first-line non-hormonal treatment, as well as sexual assessment using the PLISSIT Model according with usual care in our hospital.

The study group will be treated with a vaginal fractionated CO2 laser protocol (The SMARTXIDE TOUCH (Deka) equipment with an autoclavable vaginal probe following the manufacturer's protocol.

The control group will receive treatment with a sham-CO2 laser using a double-blinded protocol.

STUDY STRUCTURE.

SAMPLE CALCULATION Considering FSFI score as the main variable of the study, a sample size of 22 subjects for each group was calculated, accepting an alpha risk=0.05 and a beta risk \<0.1 in a bilateral contrast. The common standard deviation was considered to be of 8 points and the minimum expected effect size of 6 points. Considering follow-up loss rate of 15%, the sample size should be 51 patients.

STATISTIC ANALYSIS Descriptive statistics will be used according to standard calculation methods. The comparison between the two treatments at the end of the study will be evaluated through the change with the baseline using a mixed repeated measures model (MMRM) adjusted for the baseline value and including the treatment and the time in the model.

The variables of repetitive evaluation over time are analyzed according to the following strategy: (a) continuous variables with a repeated measures mixed longitudinal model (MMRM); (b) binary or non-normal variables with marginal models (Generalized Estimating Equation: GEE). Other variables will be studied as follows: Fisher's exact test for categorical variables, Student's t test for continuous variables between 2 groups. Non-parametric methods for independent data (Mann-Whitney U for 2 groups or Kruskall-Wallis test for more than 2 groups) will be used if necessary. The level of statistical significance will be 5% bilateral. The main analysis will be by Intention to Treat (ITT).

IMPACT:

What would be the impact of the project on sexual medicine field when it is successfully completed? Please explain how your project fits to the specific call

The BCS receiving AI are at higher risk of developing GSM symptoms. Sexual issues are common, either secondary to painful sex or as a direct effect of estrogen deprivation in the brain. However, addressing sexual health issues in BCS still meets several barriers from both, patient and health care professionals. GSM symptoms do not put survival at risk, however, have a significant impact in the quality of life.

The first-line treatment for GSM symptoms should be non-hormonal therapies according clinical guidelines, although frequently it will be insufficient to alleviate symptoms. Hormonal therapies are not currently recommended and must be used with caution in BCS. So, energy-based treatments have emerged as a promising option in this subgroup of patients. However, the body of evidence is lacking to make decisive recommendations \[18\], specially to treat sexual complaints. There is an urgent need to carry out RCT with larger sample size, long-term follow-up and blinded control group for answer various unmet needs in this field: short/mid and long-term safety issues and efficacy, treatment modalities (type of laser) and protocols (laser parameters, sessions numbers, repetitions).

This project aims to demonstrate that emergent, non-invasive, non-anesthetic laser therapy has significant benefit for BCS with AI, measured in a prospective, randomized, double-blind controlled trial using validated tools for subjective and objective sexual and vaginal health outcomes and quality of life.

Moreover, sexual health is a state of physical, emotional, mental and social well-being in relation to sexuality which requires the possibility of having pleasurable and safe sexual experiences. So, both arms of study groups will benefit from multidisciplinary approach including non-hormonal therapies (regular sexual activity, moisturizers, lubricants, pelvic floor relaxation techniques and/or dilators) and sexual assessment using the PLISSIT Model according with usual care in our hospital and with international recommendations.

randomized, double-blind, sham-controlled trial

Sexual and Vaginal Health in Breast Cancer Women Receiving Aromatase Inhibitors Before and After CO2 Laser Therapy

Sexual and Vaginal Health in Breast Cancer Women Receiving Aromatase Inhibitors Before and After CO2 Laser Therapy: A Randomized, Double-blind, Sham-controlled Trial - LIGHT Study

The 19 items of the FSFI use a 5-point Likert scale ranging from 1-5 with higher scores indicating greater levels of sexual functioning on the respective item. To score the measure, the sum of each domain score is first multiplied by a domain factor ratio (0.6 for desire; 0.3 for arousal; 0.3 for lubrication; 0.4 for orgasm; 0.4 for satisfaction; and 0.4 for pain) in order to place all domain totals on a more comparable scale, and then subsequently summed to derive a total FSFI score.

Measured by Vaginal ultrasound/vaginal biopsy.

Visual Analogue Scale of sexual life distress

Hospital Clinic of Barcelona

Principal Investigator, Clinical Professor

Atrophy

Pathological Conditions, Anatomical

Hyaluronic Acid

Mitogens

Adjuvants, Immunologic

Immunologic Factors

Viscosupplements

Protective Agents

15 female patients will receive 2 vaginal PRP injections one month apart.

15 female patients will receive 2 vaginal PRP-non-cross-linked HA injections spaced a month apart.

15 female patients will receive topical non-cross-linked hyaluronic acid gel applied every three days for 2 months as a control group

PRP can be considered a concentrate of autologous platelet-derived growth factors with known efficacy in tissue regeneration and wound healing.

Platelet rich plasma

HA filling is a known modality for rejuvenation

non cross-linked hyaluronic acid

the standard treatment of vaginal atrophy and dryness

topical HA gel

Salma Omar, MD

The goal of this clinical trial is to:

1. evaluate the efficacy of PRP injection and PRP injection mixed with non-cross-linked hyaluronic acid compared to the control group receiving standard therapy with topical non-cross-linked hyaluronic acid gel in the treatment of cancer therapy-induced or worsened vulvovaginal atrophy.
2. To evaluate the impact of vulvovaginal atrophy treatment on the sexual satisfaction of both partners.

Patients will be divided randomly into 3 groups:

Group 1: 15 female patients will receive vaginal PRP injections. Group 2: 15 female patients will receive vaginal PRP injections combined with non-cross-linked hyaluronic acid.

Group 3: 15 female patients will receive topical non-cross-linked hyaluronic acid gel as a control group.

1. The first group will receive two treatment of sub-mucosal PRP injection at the outer 3 cm of the vagina with one month interval in between. (17)
2. The second group will receive two treatment of PRP injection mixed with non-cross linked hyaluronic acid at the outer 3 cm of the vagina with one month interval in between.

9. 3-The third group will receive one applicator (5gm) three times per week of topical hyaluronic acid gel for vaginal application which will be prepared in the faculty of pharmacy for 2 months.

Clinical assessment Patients will be assessed for symptoms and signs of vulvovaginal atrophy (VVA) at baseline, one month, two months, and, three months after the end of treatment.

1. Vulvovaginal atrophy (VVA) symptoms (dryness, dyspareunia) will be assessed on a subjective 10-point scale.

   Also, patient satisfaction with each type of treatment will be assessed with a questionnaire at the end of treatment and they will be asked if they wish to repeat the treatment to maintain effectiveness over time (yes or No).
2. For assessment of VVA signs on physical examination, vaginal health index including assessment of pH, overall elasticity, epithelial mucosa, fluid secretion type, and consistency and moisture will be used as an objective method of evaluation of therapy.
3. Assessment of sexual satisfaction of both male and female partners:

Sexual satisfaction was measured using the Arabic version of the Index of Sexual Satisfaction (ISS) and female sexual function index (FSFI) questionnaire.

Management of Cancer Therapy Related Vulvovaginal Atrophy

Comparison Between Platelet-rich Plasma (PRP) and Hyaluronic Acid (HA) in the Treatment of Cancer-therapy Related Vulvovaginal Atrophy and Its Impact on Sexual Satisfaction

scores from 0-10 where 0: no symptoms, 1-3: mild symptoms, 4-6: moderate symptoms, 7-10: severe symptoms

scores range from 5-25 with lower scores signifying greater atrophy

Alexandria University

As. Prof

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Dyspareunia

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Diseases, Male

Sexual Dysfunction, Physiological

Male Urogenital Diseases

Sexual Dysfunctions, Psychological

Mental Disorders

Psychotic Disorders

Microablative Fractional CO2 Laser Therapy (The parameters that will be used are the following: 1) Power: 30 ή 40 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter from 1-3 depending on the treatment status, 5) D-pulse mode.)

Placebo therapy (The parameters that will be used are the following: 1) Power: 0.5 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter 1, 5) Smart-pulse mode.

5 laser therapies intravaginally administered will be applied at monthly intervals.

Stavros Athanasiou, Associate Professor

Athanasios Douskos, MD

Stavros Athanasiou, Prof.

Themos Grigoriadis, Assist. Prof.

Themos Grigoriadis, Assistant Proffesor

Eleni Pitsouni, MD,MSc

Stavros Athanasiou, Associate Proffesor

This study evaluates the efficacy of vaginal CO2 laser therapy in breast cancer survivors with symptoms of Genitourinary Syndrome of Menopause. Half of participants will receive active laser therapy, while the other half placebo therapy.

Vaginal Laser Therapy in Breast Cancer Survivors

Vaginal Laser Therapy for the Management of Genitourinary Syndrome of Menopause of Breast Cancer Survivors: Double-blind Randomized Placebo-controlled Trial

It is a straight line with 2 endpoints "0" and "10". Zero defines "no dyspareunia at all" and "no dryness at all" , while 10 "dyspareunia as bad as it could be" and "dryness as bad as it could be". Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of dyspareunia and dryness

Assesses frequency of urination, amount of urine, presence of urgency and/or urinary incontinence and amount of fluid intake

It includes 4 domains: activities of daily living (5 items), sexual functioning (5 items), emotional well-being (4 items), self-concept and body image (5-items). Each item of each domain could receive values from 0 to 4. Mean scores are calculated on each of the domain scales. Higher scores indicate greater symptom impact

It is a single item questionnaire assessing the impression of participants following the intervention

It is a straight line with 2 endpoints "0" and "10". Zero defines "no symptom (itching, burning and dysuria) at all" , while 10 "symptom (itching, burning and dysuria) as bad as it could be". Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of itching, burning and dysuria

It has 3 sections: 1) general health and overall health related to urinary symptoms with 2 questions, 2) incontinence impact, role limitations, physical limitations, social limitations, personal limitations, emotions, sleep and energy, and severity coping measures with 19 questions and 3) bother or impact of urinary symptoms with 11 questions. Scores of each domain of the 2 sections range from 0 to 100. Scores of the third section range from 0 to 3. Higher scores indicate higher impact of urinary incontinence.

It is a questionnaire defining women's sexual function. It includes 6 domains: desire, arousal, orgasm, lubrication, satisfaction and pain. The answer of each Question in each domain are multiplied by a certain factor. Total score is calculated by summing the scores of the all domains with a minimum value of 2 and a maximum of 36. The highest the total score the better is the sexual functioning. Total score above 26.55 defines normal sexual function

It is calculated by defining the percentage of superficial, intermediate and parabasal epithelial cells on the vaginal pap smear, following the formula (1x%superficial)+(0.5x%intermediate)+(0x%parabasal). It may receive values from 0 to 100%.It is considered to be an indicator of the estrogenic stimulation, whereas values of 0-49%, 50-64% and 65-100% indicate absent/low, moderate and high estrogenic effect on the vaginal epithelium, respectively.

It evaluates vaginal elasticity, fluid volume, ph of vaginal fluid, epithelial integrity and moisture. Each one of these may receive scores from 1 to 5. Total score is calculated by summing the 5 scores ranging from 5 to 25. Higher scores indicate better vaginal status.

it is a questionnaire with 4 questions assessing the amount of leakage, frequency and type of urinary incontinence. Total score is calculated by summing the 3 out of the 4 questions. Higher scores indicate worst urinary incontinence

It includes 12 questions assessing the quality of life and sexual satisfaction of the male partner. Each answer may receive values from 1 to 5. The higher the scores the better subjective evaluation of sexual quality of life

It is a condition specific questionnaire containing 6 questions. The answers of questions assesses the presence of symptoms and the degree of bother on a 4-point scale ("not at all", "a little bit", "moderately" and "greatly" applying to 0, 1, 2 and 3, respectively). Total score is calculated by summing the score of each question. The higher the total score the highest is the symptom bother

Biopsies will be obtained from the lateral vaginal wall. Epithelial thickness (in μ) will be measured by a vertical line between basal layer cells and superficial layers.

Biopsies will be obtained from the lateral vaginal wall. Computerized determination of blood vessels number will be performed

Biopsies will be obtained from the lateral vaginal wall. Computerized determination of the blood vessels size will be performed

Biopsies will be obtained from the lateral vaginal wall. Determination of collagen types using immunohistochemistry and microscopy.

National and Kapodistrian University of Athens

Assistant Professor

Participants will undergo two sessions of platelet-rich plasma (PRP) injections to the vulva/vagina one month apart.

0.1-0.2 mL injections of platelet-rich plasma (PRP) will be injected to the vulvovaginal area. The injections will be placed every 5mm and at an angle of 60° into the mucosa and lamina propria of the posterior wall of the vagina.

Platelet-rich plasma (PRP)

Kristin E. Rojas, MD

Kristin E Rojas, MD

The purpose of this study is to determine whether platelet rich plasma (PRP) injections to the vulva and vagina will improve symptoms of genitourinary syndrome of menopause (GSM) in breast cancer patients.

A Novel Therapy for Breast Cancer Survivors With Genitourinary Syndrome of Menopause

The VSQ is a 21-question survey that specifically asks about GSM symptoms and their impact on quality of life and sexual function. Vaginal and vulvar symptoms will be self-reported using validated VSQ modified to 4-point Likert scores. VSQ consists of a series of questions, each of which is rated as 0 (never), 1(rarely), 2(sometimes), 3 (frequently). Lower scores indicate better health. Each question is analyzed separately; there is no overall score reported.

VHI assesses post menopausal symptoms such as dryness, burning, and irritation. Each component is scored on a scale of 1 (worst) to 5 (best). Lower scores indicate more severe atrophy.

Change in validated female sexual function index (FSFI) is determined by the participant response to the female sexual function index (FSFI) questionnaire. The FSFI is a questionnaire competed by the participant and is designed to measure sexual functioning by assessing six areas of sexual function: desire, arousal, lubrication, orgasm, satisfaction, and pain. Scores range from 2 to 36. Higher scores indicate better sexual function.

Change in validated female sexual distress is determined by participant response to the female sexual distress survey-revised (FSDS-R). The FSDS-R is a self reported questionnaire that asks participants to rate distress related to low sexual desire. Responses to the items on the Likert-type scale consist of never (0), rarely (1), sometimes (2), often (3), or always (4). The lowest score that can be obtained from the FSDS-R is "0" and the highest score is "52". Higher scores indicate higher levels of sexual distress.

University of Miami

Assistant Professor of Clinical

In the active laser group, participants are treated intravaginally with the fractional microablative CO2 laser system (SmartXIDE2V2LR, MonaLisa Touch, DEKA, Florence, Italy), using the following setting; dot power 30 watt, dwell time 1000 μs, dot spacing 1000 μs and the smart stack parameter from 2 to 3. At the level of the vaginal introitus, the dot power decreases to 20 Watt.

In the sham laser group, participants are treated intravaginally with the fractional microablative CO2 laser system (SmartXIDE2V2LR, Monalisa Touch, DEKA, Florence, Italy), using the following setting; dot power 0,5 watt, dwell time 100 μs, dot spacing 2000 μs and the smart stack parameter from 1 to 1

The laser probe is gently inserted up to the top of the vagina, and subsequently withdrawn and rotated in order to deliver a complete treatment of the vaginal wall.

SmartXIDE2V2LR, Monalisa Touch, DEKA, Florence, Italy

Sine Jacobsen, MD

Pinar Bor

Sine Jacobsen

This project will be based on three studies over a period on three years. The first study is a dose response study that includes 30 breast cancer survivors. They will receive a total of 5 laser treatments with 4-6 weeks intervals The second study is a double-blind randomized controlled trial, that includes 60 breast cancer survivors. 30 of those will receive active intervention and 30 will receive placebo laser treatment and act as controls. Based on the results of the dose response study, a treatment consists of three to five laser treatments every 3 weeks. The third and last study is a one-year follow-up on study two. The conditions are evaluated before and after each treatment by questionnaires, vaginal fluid pH values, punch biopsies and vaginal and urine microbiome. The studies is conducted at the Department of Obstetrics and Gynaecology at Randers Regional Hospital in collaboration with Department of Obstetrics and Gynaecology and Department of Oncology at Aarhus University Hospital.

Vaginal CO2 Laser Therapy for Genitourinary Syndrome in Breast Cancer Survivors

Vaginal Laser Therapy for Genitourinary Syndrome in Breast Cancer Survivors - A Randomized, Blinded, Placebo-controlled Study

Participant are asked to complete the 10-cm visual analog scale (VAS) ranging for 0 to 10, with higher score indicating worse vaginal dryness.

Evaluated with visual analog scale for vaginal pain, itching, soreness. 10-cm visual analog scale (VAS) ranging for 0 to 10, with higher score indicating worse symptoms.

Sexual function parameters; desire, arousal, lubrication, orgasm, satisfaction and pain. Range 2-36, the threshold of 26.55 indicates sexual dysfunction

Addressing all domains of sexual dysfunction. Range 0-60, higher score indicate increased symptom severity

For urinary symptoms; irritative symptoms, obstructive/discomfort and stress symptoms. Range 0-18, higher score indicate higher disability

Evaluation of female sexual matters associated with their lower urinary tract symptoms. Range 0-14, higher values indicating increased symptom severity.

subjective scoring of moisture, fluid volume, epithelial integrity and elasticity and objective scoring of pH. Range 5-25, higher scores indicate better health

The biopsy of 4\*4 mm is taken from the lateralt vaginal wall, 2-3 cm from inotroitus. Afterwards fixated i formalin and the processed for light microsopy by a specialized gynaecological pathologist reporting on the changes in the histology of vaginal epithel and lamina propria.

One polyester swap (FLOQSwab) is used to sample mid-vagina for microbial analysis and immediately been placed at - 80 °C until further processing. Urine is collected in a 50 mL collection tube using the clean catch method for women. Afterwards aliquoted into 10 mL fractions and immediately been placed at - 80 °C until further processing.

DNA is isolated from samples using standard DNA isolation kits and microbiota composition determined using 16S rRNA gene sequencing. Microbiota composition is compared between groups and over time based on alpha- and beta-diversity measures, as well as changes in relative abundances of individual bacteria.

University of Aarhus

Rare Diseases

Lower Urinary Tract Symptoms

Vaginitis

Atrophic Vaginitis

Urological Manifestations

Vaginal Diseases

Oculocerebral Syndrome With Hypopigmentation

Apiwat Jongjakapun, MD

Teerayut Temtanakitpaisan, MD

Women often face common cancers like ovarian, uterine, and cervical cancers. Improvements in cancer detection and treatment mean more women survive. However, survivors can encounter challenges like ongoing pain, treatment complications, and fertility issues.

Treating these cancers often involves surgeries that might include removing ovaries or using pelvic radiation. This can trigger menopause in younger women, causing problems like vaginal dryness, itching, and urinary issues.

Women who've gone through menopause often deal with these symptoms, affecting their daily lives, confidence, and intimate relationships. Though treatments are available, lack of awareness, embarrassment, and not discussing these issues with doctors can make managing them difficult.

The main treatment for these symptoms is using vaginal estrogen, but it might not be suitable for some cancer survivors. Non-hormonal options like lubricants and moisturizers are alternatives. This study in Thailand aiming to explore how common these issues are among gynecological cancer survivors, their feelings about it, and how it affects their quality of life.

Gynecological cancers, encompassing ovarian, endometrial, and cervical cancers, stand as significant health concerns for women. In 2017, a total of 12,354 new cases were diagnosed in Thailand, underlining the prevalence and impact of these conditions. Advances in cancer screening and treatment have notably improved outcomes, resulting in a growing number of survivors. By 2016, the United States alone recorded 15.5 million cancer survivors, with projections indicating a surge to 26.1 million by 2040. However, even with increased survival rates, challenges persist for survivors, encompassing chronic pain, complications from treatment, and disruptions to fertility, menopause, sexual function, and cognitive health.

The treatment landscape for gynecological cancers is diverse, with the general principle for ovarian and endometrial cancers involving surgical staging. This comprehensive approach includes the removal of the uterus, fallopian tubes, both ovaries, peritoneum, pelvic lymph nodes, and any visible lesions. For cervical cancer, treatment varies based on disease stage. Early-stage cases often undergo surgery, potentially followed by pelvic irradiation. In advanced-stage cervical cancer, a combination of pelvic radiation and chemotherapy is commonly employed. In summary, many gynecological cancer treatments involve the removal of both ovaries or pelvic irradiation, inducing menopause in reproductive-age women.

The female lower reproductive system, including the lower urinary tract, is intricately responsive to estrogenic stimulation. When estrogen is lacking, structural changes occur, giving rise to a cluster of symptoms collectively termed the genitourinary syndrome of menopause (GSM). Estrogen deficiency results in thinning of the vaginal epithelium lining, diminished collagen and elastin fibers, reduced blood supply, and moisture decline. These changes manifest as vaginal symptoms, including burning, itching, and pain during intercourse.

Similarly, the urinary tract, deprived of estrogenic stimulation, undergoes alterations such as urethral shortening, thinning of the urethral epithelium, weakened urethral sphincter contractions, and reduced elasticity of the urinary bladder. This cascade of changes results in lower urinary tract symptoms, comprising dysuria, urinary urgency, incontinence, frequency, nocturia, and recurrent urinary tract infections.

Postmenopausal women commonly experience these symptoms, and systematic literature reviews reveal a prevalence ranging from 13 to 87%. Furthermore, the chronic nature of these symptoms tends to intensify over time. Women who undergo early bilateral oophorectomy are more likely to enter menopause sooner, increasing the risk of developing various urogenital symptoms at a younger age.

The impact of these symptoms on women's lives is profound, affecting daily activities, self-confidence, and intimate relationships. Vaginal symptoms, in particular, can lead to sexual dysfunction, exacerbating challenges in family relationships. Concurrently, urinary symptoms contribute to decreased quality of life, with frequency, nocturia, and urgency correlating with the risk of falls and bone fractures. Additionally, these symptoms are associated with depressed mood, anxiety, and embarrassment, further disrupting aspects of life such as sleep, daily commute, social interactions, and sexual relationships.

Despite the significant impact on quality of life, the effective management of vaginal and genitourinary symptoms is impeded by various factors. These include a lack of knowledge and understanding of the diseases and available treatment options, feelings of embarrassment, and the notable observation that medical personnel often fail to inquire about these specific issues during patient consultations.

The primary treatment for genitourinary symptoms is typically the use of vaginal estrogen. However, certain gynecological cancers, such as leiomyosarcoma, endometrial stromal sarcoma, and specific ovarian cancers, preclude the use of estrogen therapy. In such cases, non-hormonal alternatives like vaginal lubricants, moisturizers, and energy-based devices come into consideration.

This study aim to explore the prevalence of GSM among gynecological cancer survivors. The investigation extends to understanding the magnitude of the problem, examining women's attitudes towards the condition, and assessing its broader impact on their quality of life. This comprehensive exploration seeks to contribute valuable insights to the understanding and management of the complex challenges faced by gynecological cancer survivors.

Genitourinary Syndrome of Menopause in Thai Gynecologic Cancer Survivors

Genitourinary Syndrome of Menopause in Thai Gynecologic Cancer Survivors: A Cross-sectional Study

Prevalence of genitourinary syndrome of menopause among gynecologic cancer survivor (percent)

Severity of genitourinary syndrome of menopause measured using visual analog scale (range 0-10; 0 is the least severe, 10 is the most severe)

Quality of life score measured using a visual analog scale (range 0-10; 0 is the least negative effect on quality of life, 10 is the most negative effect on quality of life)

Assessment of attitude toward genitourinary syndrome of menopause by asking whether participant agreed with the statement or not (yes or no)

Khon Kaen University

Other Dietary Supplements

Dehydroepiandrosterone

DHEA (Dehydroepiandrosterone)

10 patients will be treated using prasterone during 6 months.

Vaginal prasterone 6,5mg/24h first month, next 5 months 6,5mg/48h, vaginal administration.

Prasterone (DHEA), Micronized

Camil Castelo-Branco

VAGINAL PRASTERONE in the treatment of VAGINAL ATROPHY IN PATIENTS WITH BREAST CANCER TREATMENT WITH AROMATASE INHIBITORS (VIBRA STUDY)

Verify a clinical improvement of AVV without increasing levels of ultrasensitive blood estradiol in breast cancer survivors treated with aromatase inhibitors by administering vaginal prasterone.

Vaginal Prasterone In Vaginal Atrophy In Breast Cancer Survivors

Vaginal Prasterone In The Treatment Of Vaginal Atrophy In Patients With Breast Cancer Treatment With Aromatase Inhibitors (Vibra Study)

Ultrasensitive blood estradiol, serum levels measured in pg/ml

vaginal pH measured by ph roll from 1 to 14 (the lesser the better)

vaginal maturation index meadured by vaginal citology on percentage from 0 to 100 divided in superficial, intermediate and basal cells. The more superficial, the better.

To describe if there is a correlation between changes in the visual examination of the vagina. using the vaginal health index: from 5 to 25 (min-max). The higher the better.

Questionaire from 18 to 90 (min-max). The higher the better.

Questionaire Social Functioning 12 (Physical and Mental Health Composite Scores) from 0 to 12 (min-max). The higher the better.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Use of Fractional CO2 Laser Versus Erbium:YAG Laser for the Treatment of GSM in Patients Using Aromatase Inhibitors	NCT05713435	Genitourinary S...	intravaginal la...	18 Years - 100 Years	Universitaire Ziekenhuizen KU Leuven
MonaLisa Laser Intervention for Post-Menopausal Breast Cancer Patients: A SHE CAN Study	NCT04606550	Breast Cancer F... Genitourinary S...	Microablative F...	18 Years - 75 Years	Mount Sinai Hospital, Canada
Sexual and Vaginal Health in Breast Cancer Women Receiving Aromatase Inhibitors Before and After CO2 Laser Therapy	NCT04619485	Breast Cancer Genitourinary S...	CO2 LASER CO2 SHAM LASER	30 Years - 80 Years	Hospital Clinic of Barcelona
Management of Cancer Therapy Related Vulvovaginal Atrophy	NCT05782920	Genitourinary S...	Platelet rich p... non cross-linke... topical HA gel	- 70 Years	Alexandria University
Vaginal Laser Therapy in Breast Cancer Survivors	NCT03738605	Genitourinary S... Vaginal Atrophy Breast Cancer Dyspareunia	Microablative F...	-	National and Kapodistrian University of Athens
MonaLisa Laser Intervention for Post-Menopausal Breast Cancer Patients: A SHE CAN Study	NCT04606550	Breast Cancer F... Genitourinary S...	Microablative F...	18 Years - 75 Years	Mount Sinai Hospital, Canada
A Novel Therapy for Breast Cancer Survivors With Genitourinary Syndrome of Menopause	NCT05812924	Breast Cancer Genitourinary S...	Platelet-rich p...	18 Years -	University of Miami
Vaginal CO2 Laser Therapy for Genitourinary Syndrome in Breast Cancer Survivors	NCT06007027	Genitourinary S...	SmartXIDE2V2LR,...	18 Years - 100 Years	University of Aarhus
Genitourinary Syndrome of Menopause in Thai Gynecologic Cancer Survivors	NCT06305494	Atrophic Vagini... Gynecologic Can... Lower Urinary T...		18 Years -	Khon Kaen University
Vaginal Prasterone In Vaginal Atrophy In Breast Cancer Survivors	NCT04705883	Vulvar Atrophy Breast Cancer Genitourinary S...	Prasterone (DHE...	-	Hospital Clinic of Barcelona
Use of Fractional CO2 Laser Versus Erbium:YAG Laser for the Treatment of GSM in Patients Using Aromatase Inhibitors	NCT05713435	Genitourinary S...	intravaginal la...	18 Years - 100 Years	Universitaire Ziekenhuizen KU Leuven

Spots Global Cancer Trial Database for genitourinary syndrome of menopause