Vaginal Moisturizer Research Articles

Association between vaginal microbiota and vaginal inflammatory immune markers in postmenopausal women.

In premenopausal individuals, vaginal microbiota diversity and lack of Lactobacillus dominance are associated with greater mucosal inflammation, which is linked to a higher risk of cervical dysplasia and infections. It is not known if the association between the vaginal microbiota and inflammation is present after menopause, when the vaginal microbiota is generally higher-diversity and fewer people have Lactobacillus dominance. This is a post hoc analysis of a subset of postmenopausal individuals enrolled in a randomized trial for treatment of moderate-severe vulvovaginal discomfort that compared vaginal moisturizer, estradiol, or placebo. Vaginal fluid samples from 0, 4, and 12 weeks were characterized using 16S rRNA gene sequencing (microbiota) and MesoScale Discovery (vaginal fluid immune markers: IL-1b, IL-1a, IL-2, IL-6, IL-18, IL-10, IL-9, IL-13, IL-8, IP10, MIP1a, MIP1b, MIP3a). Global associations between cytokines and microbiota (assessed by relative abundance of individual taxa and Shannon index for alpha, or community, diversity) were explored, adjusting for treatment arm, using linear mixed models, principal component analysis, and Generalized Linear Mixed Model + Microbiome Regression-based Kernel Association Test (GLMM-MiRKAT). A total of 119 individuals with mean age of 61 years were included. At baseline, 29.5% of participants had a Lactobacillus -dominant vaginal microbiota. Across all timepoints, alpha diversity (Shannon index, P = 0.003) was highly associated with immune markers. Individual markers that were associated with Lactobacillus dominance were similar to those observed in premenopausal people: IL-10, IL-1b, IL-6, IL-8 (false discovery rate [FDR] < 0.01), IL-13 (FDR = 0.02), and IL-2 (FDR = 0.09). Over 12 weeks, change in alpha diversity was associated with change in cytokine concentration (Shannon, P = 0.018), with decreased proinflammatory cytokine concentrations observed with decreasing alpha diversity. In this cohort of postmenopausal individuals, Lactobacillus dominance and lower alpha diversity were associated with lower concentrations of inflammatory immune markers, as has been reported in premenopausal people. This suggests that after menopause lactobacilli continue to have beneficial effects on vaginal immune homeostasis, despite lower prevalence.

Nonestrogen Therapies for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review.

To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM). MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators. We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group. Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO2) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function. Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.

P-078 In vitro effects of polycarbophil vaginal moisturizing gel on sperm motility and vitality

Abstract Study question The aim of this study was to evaluate the possible effects of intravaginal polycarbophil gel in sperm quality in an in vitro model. Summary answer Incubation of human sperm samples with a vaginal moisturizer containing polycarbophil gel 10% resulted in important reduction of sperm motility and vitality. What is known already The possible effect of lubricants on sperm quality has been a matter of debate for over 50 years. Despite the publication of a few studies, the real impact of lubricants on male gametes is remains unknown. Some commercial lubricants have been tested but so far there is a lack of studies evaluating the impact of vaginal moisturizers on seminal quality. Vaginal dryness is a recurring and significant complaint affecting couples trying to conceive who may use lubricants, vaginal moisturizers or even natural oils that could advsersely interfere with seminal quality. Study design, size, duration This paired prospective study involved seminal samples obtained fom 14 men undergoing fertility treatment at a private IVF clinic in Brazil from August/2020 to July/2022. The study was approved by the local review board and each participant signed an informed consent. Each sample was divided into two aliquots: 20% polycarbophil gel (final dilution 10%) or medium only. Statistical analysis was performed using D’Agostino/ Pearson, General Linear Model, Wilcoxon, Friedman’s. P values &amp;lt;0.05 were considered significant. Participants/materials, setting, methods Normozoospermic samples of 14 patients (alpha 0.05, power 0.8)were collected by masturbation, 2 to 5 days after the last ejaculation. After liquefaction ,10 μmL were analyzed using a Makler chamber according to World Helath Organization (WHO) guidelines. Samples were mixed 1:1 v/v with 20% policarbophil gel or with culture medium only, then incubated for 24h at 34 °c. Analysis were performed at 0, 15, 30 min and 24h to determine progressive motility and vitality (eosin-nigrosin test) Main results and the role of chance There was a significant decrease of sperm motility according to the WHO classification in both experimental conditions over time, but the reduction was more evident in the samples treated with polycarbophil gel (p &amp;lt; 0.0001 group x time, General LinearModel for Repeated Measure). The proportion of progressively motile sperm reduced immediately upon contact of the seminal sample with polycarbophil gel (time point 0 min) and decreased throughout the experiment, contrasting to incubation with culture medium (control), which only affected substantially sperm motility after 24h. In the validation cohort, the proportion of progressively motile sperm decreased from a median of 52% in fresh samples to 11% after 24h incubation with culture medium and 0% after 24h incubation with polycarbophil gel (p &amp;lt; 0.0001). Sperm vitality at the end of the experiment also differed significantly between treatments, with medians of 62.5% after exposure to culture medium and 47% after exposure to polycarbophil gel (p = 0.020, Wilcoxon’s test) Limitations, reasons for caution Results represent samples from a selected group of men undergoing fertility treatment at a private center in Brazil. The effect of polycarbophil gel in fertile males may be different. Moreover, the in vitro setting used here does not accurately mimic the vaginal environment which could interfere with the results. Wider implications of the findings Polycarbophil-based gels and similar products may harm sperm vitality and motility, therefore woment trying to conceive should avoid the use of such products until more studies prove otherwise. Trial registration number Not applicable

Satisfaction and medication adherence in women with vulvovaginal atrophy: the CRETA

Objective This study aimed to evaluate the self-reported satisfaction of Spanish postmenopausal women currently treated for vulvovaginal atrophy (VVA) symptoms. Methods The CRETA (CRoss sectional European sTudy on Adherence) is a multicenter cross-sectional study conducted in 29 public and private hospitals in Spain, which enrolled postmenopausal women receiving treatment with ospemifene, local hormone therapy (HT) or vaginal moisturizers for VVA. After the prior informed consent of the patients, sociodemographic and treatment perception data were collected using a structured questionnaire. Results Among 752 women who completed the survey, the satisfaction score was significantly higher for the group treated with ospemifene (mean 8.3 ± 1.4) compared with the local HT group (7.2 ± 1.7) and the vaginal moisturizer group (6.5 ± 2.1) according to a 10-point Likert scale (p < 0.0001). Compared to vaginal moisturizers and local HT, participants treated with ospemifene reported the highest adherence (96.7% vs. 70.2% and 78.6%, respectively) and the lowest number of missed doses in the last month (0.6 ± 1.3 standard deviation [SD] vs. 3.5 ± 4.3 SD and 2.0 ± 2.8 SD, respectively) (p < 0.0001). Ospemifene was significantly perceived as easy to use (83.9% vs. 44.9% and 58.6%, respectively; p < 0.0001), efficacious in reducing the time to relieve symptoms (17.1% vs. 7.0% and 6.7%, p = 0.0005 and p = 0.0006, respectively) and convenient for sexual life (53.1% vs. 25.6% and 42.3%, p < 0.0001 and p = 0.0234, respectively). Conclusions Among postmenopausal women with VVA, treatment with ospemifene has the most positive perceptions and the highest overall satisfaction level and could be an optimal therapeutic approach, maximizing patient adherence.

New vaginal moisturizer is well-accepted and reduces symptoms related to the genitourinary syndrome of menopause in Brazilian women

Objectives: To evaluate the effectiveness and acceptability of a new vaginal moisturizer composed of a combination of humectants, moisturizers, bioadhesives, and viscosity polymers (sodium hyaluronate 0.1%, polycarbophil 1.5%, carbomer 1.5%, and glycerin 1%) for relief of vulvovaginal symptoms associated with genitourinary syndrome of menopause in Brazilian postmenopausal women. Methods: An open clinical trial was performed with 33 postmenopausal women between 47 and 68 years of age with genitourinary syndrome of menopause symptoms such as vaginal dryness accompanied by pain or discomfort during intercourse. Clinical efficacy in relieving symptoms of genitourinary syndrome of menopause and acceptability were assessed using a Likert scale questionnaire. Efficacy and safety were assessed through gynecological examination, which included visual inspection of the epithelium and vaginal contents, and determination of vaginal pH. Wilcoxon's non-parametric test and paired Student's t-test were used for statistical analyses.Results: After 3 weeks of treatment, most participants reported improvement in GSM symptoms like vaginal dryness (p&lt;0.001), discomfort during or after sexual intercourse (p&lt;0.001), pain during or after sexual intercourse (p&lt;0.001), vaginal odor (p=0.047) and itching (p=0.032) and good acceptability of the moisturizer. There was no alteration in the vaginal health index; however, a reduction in vaginal inflammation (p=0.046) was observed. No clinically significant adverse events were reported by participants. Conclusions: Treatment with non-hormonal vaginal moisturizer for 3 consecutive weeks in postmenopausal women with symptoms of genitourinary syndrome of menopause promoted improvements in vaginal hydration, showing a clinically adequate profile of efficacy and safety, in addition to a satisfactory degree of acceptability.

Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy

Among treatments for vulvo-vaginal atrophy (VVA), there is a new kind of energy-based device, the non-ablative CO2 laser. This study aimed to assess the efficacy and safety of the non-ablative CO2 laser in menopausal women with VVA as a monotherapy or in association with vaginal estriol or moisturizer. Seventy-five women with VVA received laser treatment (Laser group), laser plus estriol gel (Laser+E) or laser plus moisturizers (Laser+M). The study protocol consisted of 3 monthly laser sessions (t0, t1, t2) and a gynecological examination at baseline and 1 month after last laser treatment (t3). Objective measures included VHI (Vaginal Health Index) and VuHI (Vulvar Health Index); subjective symptoms of VVA (Dryness, Burning, Itching, Dysuria) evaluated via visual analog scales, sexual function evaluated by FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Score) and MENQOL (Mopause-specific Quality Of Life). Adverse events and discomfort encountered during the procedure were also assessed. Primary outcomes were the evaluation of VHI and VuHI and secondary outcomes were changes in VVA symptoms (VAS), sexual function (MENQOL, FSFI, FSDS) and discomfort during the procedure. Seventy-five women (25 in Laser, 25 in Laser+E and 25 in Laser+M group) completed the study. At t3, mean VHI, VuHI, dryness, burning and itching VAS scores improved significantly with no differences between the groups. The lubrication domain of FSFI improved significantly only in the Laser+M group, while the pain domain improved significantly in all women with no differences between the groups. FSFI and FSDS overall scores and MENQOL sexual domain improved in all women with no significant difference between the groups. The mean score of the pain during the procedure was low at t0 and did not change throughout the study. This study extends knowledge concerning the effectiveness of a new non-ablative CO2 laser in post-menopausal women with VVA. This is one of the first studies on this kind of laser and is the first to compare the effectiveness of laser treatment alone or in combination with vaginal estriol or moisturizers. Parameters of VVA and sexual function were evaluated using validated tools. Study limitations include short follow-up time, the limited number of participants and the absence of a sham-controlled group. Non-ablative CO2 laser seems to be an effective treatment for VVA in menopausal women. Our preliminary data shows that it can be effective as monotherapy or with adjuvant treatments.

Impact of Topical Interventions on the Vaginal Microbiota and Metabolome in Postmenopausal Women

Postmenopausal women with genitourinary symptoms of menopause are often prescribed vaginal estradiol or moisturizer for symptom improvement, but the impact of these treatments on the local microenvironment is poorly understood. To compare changes in the vaginal microbiota, metabolome, and pH among women using low-dose vaginal estradiol tablet or low pH moisturizer gel for 12-weeks vs low pH placebo. This is a post hoc prespecified secondary analysis of a 12-week multicenter randomized clinical trial among postmenopausal women with moderate to severe genitourinary symptoms. Women were enrolled between April 2016 and February 2017; final follow-up visits occurred in April 2017. Data were analyzed from November 2018 to July 2021. Ten-μg vaginal estradiol plus placebo gel vs placebo tablet plus vaginal moisturizer vs dual placebo. The main outcome measures were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Of 302 postmenopausal women from the parent trial, 144 women (mean [SD] age, 61 [4] years) were included in this analysis. After 12 weeks, the microbiota was dominated with Lactobacillus and Bifidobacterium communities among 36 women (80%) in the estradiol group, compared with 16 women (36%) using moisturizer and 13 women (26%) using placebo (P < .001). The composition of vaginal fluid metabolites also varied after 12-weeks among women in the estradiol group with significant changes in 90 of 171 metabolites measured (53%) (P < .001), including an increase in lactate. The 12-week pH among women in the estradiol group was lower vs placebo (median [IQR] pH, 5 [4.5-6.0] vs 6 [5.5-7.0]; P = .005) but not the moisturizer group vs placebo (median [IQR] pH, 6 [5.5-6.5]; P = .28). There was a decrease in pH from baseline to 12-weeks within the moisturizer (median [IQR] pH, 7 [6.0-7.5] vs 6 [5.5-6.5]; P < .001) and placebo (median [IQR] pH, 7 [7.0-7.5] vs 6 [5.5-7.0]; P < .001) groups. Women with high-diversity bacterial communities at baseline exhibited greater median change in pH compared with women with low-diversity communities (median [IQR] change, -1 [-2 to -0.5] vs -0.3 [-1.1 to 0], P = .007). This secondary analysis of a randomized clinical trial found that use of vaginal estradiol tablets resulted in substantial changes in the vaginal microbiota and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline. Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH. Estradiol use may offer additional genitourinary health benefits to postmenopausal women. ClinicalTrials.gov Identifier: NCT02516202.

Polycarbophil vaginal moisturizing gel versus hyaluronic acid gel in women affected by vaginal dryness in late menopausal transition: A prospective randomized trial

ObjectivesDuring menopausal transition, women are frequently affected by vulvovaginal atrophy (VVA), due to the decline of estrogen levels. Resulting symptoms are itching, burning, dyspareunia, and vaginal dryness (reported in up to 85%). The aim of this trial was to verify if medical device polycarbophil vaginal (PCV) moisturizer gel is not less effective than hyaluronic acid (HA) gel in treating vaginal dryness. Material and methodsThis was a multicenter, open label, randomized, parallel group, comparative study with non-inferiority design. Female included were ≥45 to ≤55 years in the menopausal transition, with subjective dryness, any objective sign of VVA, pH > 5, and body mass index of ≥18.5 to ≤36 kg/m2. Subjects were randomized to 1 g of PCV gel twice a week for 30 days or 3 g of HA vaginal gel every 3 days for 30 days. Results53 subjects (mean age 49.45 ± 2.96 years) were analyzed. Vaginal health index showed an improvement (p < 0.001) in both groups (from 12.54 ± 1.37 to 16.36 ± 2.66 for PCV, from 12.00 ± 1.91 to 16.60 ± 2.50 for HA), but the difference between final means (95%CI: −1.66 to 1.18) evidenced that PCV is non-inferior to HA treatment. Similarly, an improvement was evidenced in vaginal maturation index (p = 0.005 for PCV, ns. for HA), female sexual function index (p < 0.001 for PCV, p < 0.001 for HA), and SF-12 (p < 0.001 for PCV, p < 0.001 for HA), with no difference between groups. Safety was optimal and no adverse events were reported. ConclusionsThe use of HA gel does not give additional benefits to those that are already provided by the moisturizing PCV.

How to choose the right vaginal moisturizer or lubricant for your patient

How to choose the right vaginal moisturizer or lubricant for your patient

Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation

Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.

A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors

ObjectiveTo assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer. MethodsFor this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12–14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4–6 weeks [T2]; 12–14 weeks [T3]; 22–24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). ResultsOf 43 patients, mean age was 59 years (range, 38–78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41). ConclusionThe HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1–2×/week is recommended for women in natural menopause; a 3–5×/week schedule appears more effective for symptom relief in cancer survivors.

MsFLASH network vaginal health trial: absence of evidence is NOT evidence of absence

Approximately 50% of postmenopausal women experience vulvovaginal symptoms associated with genitourinary syndrome of menopause (GSM). GSM is a chronic and progressive condition with a well-defined treatment algorithm. Analysis of the MsFLASH Vaginal Health Trial data produced two main conclusions, which were that prescribed vaginal 10 μg estradiol tablet and over-the-counter (OTC) vaginal moisturizer did not provide additional benefit over placebo vaginal tablet and placebo gel in reducing postmenopausal vulvovaginal symptoms; or increasing the proportions of women reporting sexual activity or improving pain scores with sexual activity. These treatment conclusions are contrary to all prior robust clinical trial data for dyspareunia and vaginal dryness, and not in line with the good clinical practice for GSM management presented by the American College of Obstetricians and Gynecologists, The North American Menopause Society, and the Endocrine Society. Overall, the flaws of the MsFLASH Vaginal Health Trial were to incorrectly identify the therapeutic outcomes of most interest using metrics that exhibit high degrees of placebo bias; and to utilize low statistical power with which to appreciate any significant differences between groups.

A single-arm, prospective trial investigating the effectiveness of a non-hormonal vaginal moisturizer containing hyaluronic acid in postmenopausal cancer survivors.

To assess the feasibility and efficacy of a non-hormonal hyaluronic acid (HLA) vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in postmenopausal women with a history of hormone receptor-positive (HR+) cancer. For this single-arm, prospective longitudinal trial, we identified disease-free patients with a history of HR+ breast cancer treated with aromatase inhibitors or HR+ endometrial cancer treated with surgery and postoperative radiation. Participants used HLA daily for the first 2weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1], 4-6weeks [T2], 12-14weeks [T3], 22-24weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). Of 101 patients, mean age was 55years (range, 31-78), 68% (n = 69) were partnered, and 60% (n = 61) were sexually active. In linear mixed models, VAS/VuAS scores significantly improved at all assessment points (all p < 0.001). MSCL scores similarly improved (all p < 0.001). FSFI scores significantly improved from T1 to T2 (p < 0.03), T3 (p < 0.001), and T4 (p < 0.001). Severe vaginal pH (> 6.5) decreased from 26% at T1 to 19% at T4 (p = 0.18). HLA moisturization improved vulvovaginal health/sexual function of cancer survivors. While HLA administration 1-2×/week is recommended for women in natural menopause, a 3-5×/week schedule appears to be more effective for symptom relief in cancer survivors.

Lights on MsFLASH: a review of contributions.

The Menopause Strategies: Finding Lasting Answers for Symptoms and Health clinical trials network was funded by the National Institutes of Health to find new ways to alleviate the most common, bothersome menopausal symptoms by designing and conducting multiple concurrent clinical intervention studies, accommodating a wide scope of populations and intervention strategies. Trials were conducted in Boston, Indianapolis, Minneapolis, Oakland, Philadelphia, and Seattle, with the Data Coordinating Center in Seattle, and were designed with standardized eligibility criteria and endpoints. Primary outcomes focused on vasomotor symptoms, sleep quality and insomnia symptoms, and vaginal symptoms. Secondary outcomes included quality of life, sexual function, and mood. We completed five randomized clinical trials and three ancillary studies, testing nine interventions in over 1,300 women and collecting nearly 16,000 bio-specimens. Escitalopram, venlafaxine hydrochloride extended release, and low-dose estradiol diminished hot flashes by approximately 50% as compared with a 30% decrease by placebo. No benefits on vasomotor symptoms were observed with yoga or exercise compared with usual activity, nor with omega-3 supplementation compared with placebo. Cognitive behavioral therapy for insomnia reduced self-reported insomnia symptoms and improved overall sleep quality compared with menopause education control. We did not find significant benefit from a vaginal estradiol tablet or a vaginal moisturizer compared with placebo tablet and gel in diminishing the severity of vaginal symptoms. The MsFLASH trials contributed substantially to our understanding of bothersome menopausal symptom treatment. It is important that clinicians counseling women about available treatment options consider all therapies-both nonhormonal and hormonal.

Patient-centered change in the day-to-day impact of postmenopausal vaginal symptoms: results from a multicenter randomized trial

Vulvovaginal symptoms, which include dryness, irritation, and pain with intercourse, are common among postmenopausal women and are associated with impaired sexual functioning and quality of life. Previous assessment of treatment strategies for these symptoms has been limited by a lack of sensitive patient-centered outcome measures that assess symptom impact on functional and quality-of-life domains. We aimed to (1) examine change in the impact of postmenopausal vulvovaginal symptoms on multiple aspects of well-being and functioning in relation to vaginal estradiol and moisturizer treatment and (2) guide meaningful interpretation of scores on a structured-item questionnaire measure of condition-specific impact. Data were drawn from postmenopausal women who were enrolled in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health Vaginal Health Trial (a 12-week, double-blind, placebo-controlled randomized trial of treatment for vulvovaginal symptoms) who were assigned to vaginal 10-μg estradiol tablet plus placebo gel (n=98), vaginal moisturizer plus placebo tablet (n=97), or dual placebo (n=94). At baseline and 12-week follow up, participants completed the Day-to-Day Impact of Vaginal Aging questionnaire to assess the impact of vaginal symptoms on 4 domains (activities of daily living, emotional well-being, sexual functioning, and body image), each on a 0-4 point scale. Day-to-Day Impact of Vaginal Aging sensitivity to change was assessed by the examination of the associations between change in Day-to-Day Impact of Vaginal Aging domain scores and vulvovaginal symptom severity from baseline to 12 weeks with analysis of covariance. Within-woman and between-group minimal clinically important improvement was assessed with the use of an anchor-based approach that relates change in Day-to-Day Impact of Vaginal Aging domain scores with self-reported benefit from treatment. Participants in all treatment arms (n=289) demonstrated reduced impact of vulvovaginal symptoms on all domains of well-being and functioning as assessed by Day-to-Day Impact of Vaginal Aging at 12-week follow up, with no significant differences in improvement between women who were assigned to either estradiol tablet or vaginal moisturizer compared with placebo. For all Day-to-Day Impact of Vaginal Aging domains, mean impact scores were reduced when participants reported symptom improvement (-0.3 to -0.8 point change in Day-to-Day Impact of Vaginal Aging scores for <2-point symptom severity change vs -0.4 to -1.6 point change in Day-to-Day Impact of Vaginal Aging scores for 2+ point symptom severity change; all P<.001). Minimal clinically important change in Day-to-Day Impact of Vaginal Aging domain scale scores, which are anchored to self-reported meaningful benefit from treatment at 12 weeks, ranged from -0.4 to -1.3 (within-woman) and -0.2 to -0.7 (between-group). Observed change and minimal clinically important difference were largest for the sexual functioning domain. The impact of vulvovaginal symptoms on day-to-day activities, sexual function, emotional well-being, and body image may be improved with low-dose vaginal estradiol, moisturizer, or topical placebo. The Day-to-Day Impact of Vaginal Aging questionnaire demonstrates sensitivity to change with treatment of vulvovaginal symptoms, particularly Day-to-Day Impact of Vaginal Aging scales that focus on symptom impact on sexual functioning and body image. Minimal clinically important improvement in the impact of vulvovaginal symptoms as measured by the Day-to-Day Impact of Vaginal Aging can be defined with the use of these measures.

Convergent-Divergent Validity and Correlates of the Day-to-Day Impact of Vaginal Aging Domain Scales in the MsFLASH Vaginal Health Trial

IntroductionClinical research and management of postmenopausal vaginal symptoms have been limited by the lack of validated measures for assessing symptom impact. AimTo evaluate convergent-divergent validity of the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire among postmenopausal women with moderate-to-severe vulvovaginal symptoms and identify demographic and clinical factors associated with greater symptom impact. MethodsWe examined baseline data from postmenopausal women with moderate-to-severe vulvovaginal itching, pain, irritation, dryness, or pain with intercourse in a randomized trial of vaginal estradiol, moisturizer, or placebo. In addition to completing the DIVA questionnaire, participants rated the severity of their most bothersome vulvovaginal symptom, underwent assessment of vaginal pH and epithelial cytology, and completed other self-report measures including the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), and Patient Health Questionnaire-8 for depression (PHQ-8). Main Outcome MeasureThe main outcome measures were the unadjusted correlations and multivariable-adjusted associations with 4 DIVA domain scales designed to assess symptom impact on day-to-day activities, sexual functioning, emotional well-being, and body image/self-concept on a scale of 0 to 4. ResultsAmong 301 women, we detected moderately strong correlations between the DIVA emotional well-being scale and PHQ-8 scores (Pearson correlation coefficient [r] = 0.39) and strong correlations between the DIVA sexual functioning scale and FSFI and FSDS scores (r > 0.50). No significant correlations were detected between any DIVA scales and vaginal pH or epithelial cytology. In adjusted linear-regression analyses, greater vulvovaginal symptom severity was associated with worse DIVA scores for emotional well-being, sexual functioning, and self-concept/body image (average 0.3- to 0.5-point higher DIVA score for each 1-point difference in vulvovaginal symptom severity). Depression symptoms were associated with worse DIVA scores for activities of daily living and emotional well-being (0.2- to 0.4-point higher DIVA score for each 5- point worsening of PHQ-8 score). Women reporting recent sexual activity had lower symptom impact on sexual functioning and self-concept/body image domains (−0.3- to −0.4-point lower DIVA score with weekly sexual activity). Clinical ImplicationsFindings suggest that the impact of postmenopausal vaginal symptoms on functioning and well-being is greater in women with co-morbid depression symptoms and less frequent sexual activity, independent of symptom severity. Strengths & LimitationsStrengths include the multicenter sample and wide array of measures. Results may not generalize to women with mild symptoms. ConclusionOur results support the construct validity of the DIVA questionnaire for clinical practice and research and indicate that depression and lower frequency of sexual activity are markers of greater impact of postmenopausal vaginal symptoms on multiple dimensions of functioning and quality of life.Hunter MM, Guthrie KA, Larson JC, et al. Convergent-Divergent Validity and Correlates of the Day-to-Day Impact of Vaginal Aging Domain Scales in the MsFLASH Vaginal Health Trial. J Sex Med 2020;17:117–125.

A Single-Arm Clinical Trial Investigating the Effectiveness of a Non-Hormonal Vaginal Moisturizer in Endometrial Cancer Survivors

A Single-Arm Clinical Trial Investigating the Effectiveness of a Non-Hormonal Vaginal Moisturizer in Endometrial Cancer Survivors

A single-arm clinical trial investigating the effectiveness of a non-hormonal vaginal moisturizer in postmenopausal cancer survivors

A single-arm clinical trial investigating the effectiveness of a non-hormonal vaginal moisturizer in postmenopausal cancer survivors

Sexual frequency and pain in a randomized clinical trial of vaginal estradiol tablets, moisturizer, and placebo in postmenopausal women.

To evaluate the efficacy of two common interventions for bothersome postmenopausal vaginal symptoms on improving sexual frequency and pain. This is a post-hoc analysis of data from a 12-week double-blind placebo-controlled trial that randomized postmenopausal women (ages 45-70 years) with moderate-severe genitourinary discomfort to vaginal 10 μg estradiol tablet plus placebo gel (n = 102), placebo tablet plus vaginal moisturizer (n = 100), or dual placebo (n = 100). Outcomes were proportion of sexually active women at 12 weeks, frequency of sexual activity, and pain severity with sexual activity (0-3 scale). Consistent with the original study design, comparisons were made between each active arm and the dual placebo arm. Most women enrolled in the trial, 294/302 (97%), had sufficient data to be included in this analysis. Mean age of participants was 61 years, most were white (88%), college educated (66%), and most reported sexual activity in the month before enrollment (81%). After 12 weeks of treatment, a similar proportion of women in the vaginal estrogen and dual placebo groups reported sexual activity in the past week (50% and 40%; P = 0.10) and the past month (78% and 84%, P = 0.52). Mean (standard deviation) pain with sexual activity scores at 12 weeks were similar between vaginal estrogen (1.0 [1.0]) and placebo (0.9 [0.9], P = 0.52] groups. The proportion sexually active at 12 weeks (35%) and mean (standard deviation) pain severity in the vaginal moisturizer group (1.1 [0.9]) did not differ from placebo (P = 0.36). Compared to placebo, neither low-dose vaginal estradiol nor vaginal moisturizer treatment over 12 weeks resulted in significantly greater increases in the proportions of women reporting sexual activity or improvement in pain scores with sexual activity. Clinical trials.gov: NCT02516202.

Re: Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: .

Re: Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: .