Prospective, multicenter, uncontrolled study on the effectiveness and safety of a hyaluronic acid water-based vaginal lubricant in alleviating vaginal dryness and dyspareunia.

BACKGROUND: Vaginal dryness (VD) represents a significant concern affecting women across diverse life stages, encompassing both pre- and postmenopausal women at any age. Dyspareunia, defined by genital pain that can be experienced before, during, or after intercourse, is often associated with vaginal dryness. AIM: This study aimed to evaluate the effectiveness and safety of a water-based vaginal lubricant with hyaluronic acid to reduce sexual discomfort associated with vaginal dryness. METHODS: A prospective, multicenter, uncontrolled clinical investigation was conducted over a three-month period in women aged 18 years or older experiencing pain or difficulty during sexual intercourse for whom the use of a vaginal lubricant was recommended. RESULTS: Significant improvements were observed in the FSFI scores, indicating enhanced sexual function (p < .001). Vaginal dryness symptoms, including irritation, dryness, itching, and dyspareunia, significantly decreased after product use (p < .001). CLINICAL IMPLICATIONS: This study contributes to the limited scientific knowledge on the application of lubricants in the context of symptoms associated with VD. STRENGTHS & LIMITATIONS: In addition to the short study period, inherent limitations of the study design, and lack of placebo control, it is pertinent to acknowledge that some of the pros used in this study were not based on validated questionnaires. However, as far as we know, this study is the only one that analyzes well-being and sexual pleasure as results using a lubricant formulated with hyaluronic acid. CONCLUSION: This tested vaginal lubricant with hyaluronic acid has demonstrated efficacy in improving vaginal dryness and female sexual function, particularly in reducing pain and improving lubrication during sexual intercourse, and showed a favorable safety profile, with minimal and transient adverse events.

A randomized trial on the effectiveness and safety of 5 water-based personal lubricants.

BACKGROUND: A range of personal lubricants with different formulations and subsequent properties are available for relief of discomfort associated with vaginal dryness; however, there are limited clinical data to support the efficacy and safety of many commercially available lubricants. AIM: To determine the effectiveness and safety of 5 water-based personal lubricants for the relief of intimate discomfort associated with vaginal dryness in pre- and postmenopausal women: 4 that were formulated to meet the World Health Organization (WHO) guidelines for osmolality and pH and 1 preexisting lubricant of higher osmolality and pH. METHODS: An open-label, parallel-design study was performed in women aged 18 to 65 years with mild-to-moderate vaginal dryness and dyspareunia. Participants were randomized to 1 of 5 lubricants (A-E) from 3 brands (Durex, KY, Queen V). They were instructed to use their allocated lubricants during vaginal intercourse at least once a week over a 4-week period. The Female Sexual Function Index (FSFI) measured sexual functioning after 4 weeks of use as an indicator of lubricant performance. OUTCOMES: The primary outcome was change from baseline in total FSFI score after 4 weeks of product use. RESULTS: A total of 174 women completed the study. The primary end point-a prespecified increase in FSFI ≥4 points from baseline after 4 weeks of use-was met by all 5 lubricants tested. A statistically significant improvement was observed across all 6 domains of the FSFI from baseline to 4 weeks of use with all 5 lubricants (P < .0001 for lubrication and pain reduction and P < .05 for all other domains). No serious adverse events occurred in the study, and the tolerance of all 5 lubricants was good/very good. CLINICAL IMPLICATIONS: The efficacy and safety of the tested lubricants are not compromised when formulated to meet the WHO criterion of osmolality ≤1200 mOsm/kg. The lubricants tested in this investigation can be used not only to relieve symptomatology of vaginal dryness and dyspareunia but also to enhance overall sexual satisfaction. STRENGTHS AND LIMITATIONS: This study provides clinical evidence for the efficacy and safety of 5 lubricants, including those formulated to meet WHO guidelines, in relieving symptoms of vaginal dryness and improving the overall sexual experience. The open-label design may have introduced bias into the study. CONCLUSION: All 5 lubricants, including those formulated to be compliant with guidelines on pH and osmolality, can be considered effective and well tolerated for the relief of discomfort associated with vaginal dryness.

Effect of topical oxytocin gel on vaginal mucosa in postmenopausal Egyptian women: a clinical randomized trial.

BACKGROUND: Vaginal atrophy is common after menopause and is often linked to sexual dysfunction, particularly dyspareunia. AIM: The study aimed to investigate the effect of intravaginally applied oxytocin on expressions of vaginal atrophy. METHODS: Fifty postmenopausal women aged 47 to 66 years with vaginal atrophy participated in this double-blinded placebo-controlled study. The women were randomized to intravaginal treatment with either gel with 600 IU/mL of oxytocin (oxytocin group) or gel alone (control group) once daily for 2 weeks. The gel consisted of hypromellose, pH 3.8 (Vagovital). OUTCOMES: The color of the vaginal mucosa, the vaginal pH, and the cytology of vaginal epithelial cells were investigated before and after treatment. RESULTS: The color of the vaginal mucosa shifted from pale to red in all 25 patients treated with oxytocin but only in 4 patients in the control group (P < .001). There was a significant decrease in intravaginal pH in the oxytocin group and the control group, with the delta value being significantly greater in the oxytocin group than in the control group (P < .001). The vaginal maturation index increased significantly (P < .001) in the oxytocin group but not in the control group. CLINICAL IMPLICATIONS: Topical oxytocin gel offers an effective solution to the sexual dysfunction that is related to vaginal atrophy after menopause. STRENGTHS AND LIMITATIONS: Strengths include studying different outcomes of applying the oxytocin gel for vaginal atrophy. Limitations include the small-scale population with a relatively short duration of treatment (2 weeks). CONCLUSION: Intravaginal treatment with a gel containing 600 IU/mL of oxytocin effectively counteracts physical expressions of vaginal atrophy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05275270; https://clinicaltrials.gov/ct2/show/NCT05275270).

Low genitourinary tract risks in women living with the human immunodeficiency virus.

This review analyzes the clinical associations between specific low genitourinary tract clinical circumstances in perimenopausal and postmenopausal women living with human immunodeficiency virus (WLHIV). Modern antiretroviral therapy (ART) improves survival and reduces opportunistic infections and HIV transmission. Despite appropriate ART, WLHIV may display menstrual dysfunction, risk of early menopause, vaginal microbiome alterations, vaginal dryness, dyspareunia, vasomotor symptoms and low sexual function as compared to women without the infection. They have increased risks of intraepithelial and invasive cervical, vaginal and vulvar cancers. The reduced immunity capacity may also increase the risk of urinary tract infections, side-effects or toxicity of ARTs, and opportunistic infections. Menstrual dysfunction and early menopause may contribute to the early onset of vascular atherosclerosis and plaque formation, and increased osteoporosis risks requiring specific early interventions. On the other hand, the association between being postmenopausal and having a low sexual function is significant and related to low adherence to ART. WLHIV deserve a specific approach to manage different low genitourinary risks and complications related to hormone dysfunction and early menopause.

Pharmacokinetics, safety and preliminary pharmacodynamic evaluation of DARE-VVA1: a soft gelatin capsule containing tamoxifen for the treatment of vulvovaginal atrophy.

OBJECTIVE: This study aimed to measure safety, systemic pharmacokinetics and preliminary efficacy of a vaginal tamoxifen capsule (DARE-VVA1) among postmenopausal women with moderate-to-severe vulvovaginal atrophy. METHODS: This was a randomized, placebo-controlled, double-blind, phase 1/2 study of DARE-VVA1, in four doses (1, 5, 10 and 20 mg). RESULTS: Seventeen women were enrolled and 14 completed the 8-week treatment. DARE-VVA1 was safe. All adverse events were of mild or moderate severity and distributed similarly among active and placebo groups. Plasma tamoxifen concentrations were highest among women using DARE-VVA1 20 mg, but the maximum mean (standard deviation) plasma tamoxifen concentrations on day 1 (2.66 ± 0.85 ng/ml) and day 56 (5.69 ± 1.87 ng/ml) were <14% of those measured after one oral tamoxifen dose. Active study product users had significant decreases from pre-treatment baseline in vaginal pH and proportion of vaginal parabasal cells (p = 0.04 for both endpoints), with women randomized to the 10 mg or 20 mg dose experiencing the largest treatment impact. The severity of vaginal dryness and dyspareunia decreased significantly from baseline with active study product use (p = 0.02 for both endpoints). CONCLUSIONS: DARE-VVA1 is safe and results in minimal systemic exposure to tamoxifen. Preliminary efficacy data support further development of this product.

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.

Vulvovaginal atrophy in the CRETA study: the healthcare professionals' perception.

OBJECTIVES: The objective is to assess the perception of gynecologists regarding patients' adherence to vulvovaginal atrophy (VVA) treatments, to evaluate the gynecologists' opinions on what their patients think about treatment adherence, and to compare the gynecologists' opinions with the patients' own perceptions within the CRETA study. METHODS: Spanish gynecologists who participated in the CRETA study were asked to fill out an online 41-item questionnaire to evaluate their views on VVA management. RESULTS: From 29 centers across Spain, 44 gynecologists completed the survey. Their mean age was 47.2 years old, two-thirds of them were women, and the average professional experience was over 20 years. According to the gynecologists, the therapy most frequently used by VVA-diagnosed women was vaginal moisturizers (45.5%), followed by local estrogen therapy (36.4%) and ospemifene (18.2%). Nevertheless, ospemifene was viewed as the therapeutic option with the most efficacy, easiest route of administration, shorter time to symptom improvement, lower percentage of dropouts, and higher treatment adherence. CONCLUSIONS: Spanish gynecologists are in general agreement with their patients regarding VVA treatment preferences and the main issues for adherence and effectiveness. However, there is an opportunity for doctor-patient communication improvement. Among the three therapeutic options evaluated, ospemifene is regarded as offering some competitive advantages.

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

BACKGROUND: Among treatments for vulvo-vaginal atrophy (VVA), there is a new kind of energy-based device, the non-ablative CO2 laser. AIM: 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. METHODS: 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. OUTCOMES: 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. RESULTS: 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. CLINICAL IMPLICATIONS: This study extends knowledge concerning the effectiveness of a new non-ablative CO2 laser in post-menopausal women with VVA. STRENGTHS & LIMITATIONS: 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. CONCLUSION: 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. Alvisi S, Lami A, Baldassarre M, et al. Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy. J Sex Med 2022;19:761-770.

Efficacy of intradermal hyaluronic acid plus polynucleotides in vulvovaginal atrophy: a pilot study.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of vulvovaginal intradermal injections of polynucleotides (PN) combined with hyaluronic acid (HA) in postmenopausal women affected by vulvovaginal atrophy (VVA). MATERIALS AND METHODS: Postmenopausal women affected by VVA were treated with vulvar and vaginal intradermal injections of one prefilled syringe of 2 ml PN/HA every 2 weeks for four sessions. Patients were evaluated at T0 (baseline), T1 (after session 4) and T2 (1 month after session 4). Evaluation of the treatment was assessed by three international validated questionnaires: Vaginal Health Index (VHI), Vulvar Health Index (VuHI) and Female Sexual Function Index (FSFI). The Wilcoxon matched-paired signed-rank test was used to compare the differences in VHI, VuHI, FSFI and FSFI domains within the groups. Statistical significance was set at p < 0.05. RESULTS: Fifty patients were included in the study (mean age 59.9 ± 7.6 years). Overall, the VHI, VuHI and FSFI reported statistically significant differences between baseline and T1 (p < 0.001) and between baseline and T2 (p < 0.001). All FSFI domains registered a statistically significant increase between baseline and T2 (p < 0.001). No complications or side effects were observed. CONCLUSIONS: Vulvovaginal intradermal injection of PN/HA is a safe, effective treatment, is not expensive and is a reproducible procedure in postmenopausal women with VVA.

The therapeutic effect of dehydroepiandrosterone (DHEA) on vulvovaginal atrophy.

Vulvovaginal atrophy (VVA) is a chronic disease that mostly occurs in postmenopausal women. After menopause, insufficient sex hormones affect the anatomy of the vagina and cause drastic physiological changes. The main histopathological studies of VVA show that postmenopausal estrogen deficiency can lead to the increase of intermediate/parabasal cells, resulting in the loss of lactobacillus, elasticity and lubricity, vaginal epithelial atrophy, pain, dryness. Although the role of estrogen hormones in the treatment of VVA has always been in the past, it is now widely accepted that it also depends on androgens. Estrogen drugs have many side effects. So, Dehydroepiandrosterone（DHEA）is promising for the treatment of VVA, especially when women with contraindications to estrogen have symptoms. This review is expected to understand the latest developments in VVA and the efficacy of DHEA.

Hyaluronic Acid in Postmenopause Vaginal Atrophy: A Systematic Review.

BACKGROUND: The decline in postmenopausal serum estrogen concentration results in several changes in the vulvovaginal and vesicourethral areas, resulting in the genitourinary syndrome of menopause, including symptoms such as vaginal atrophy. AIM: To evaluate the effects of hyaluronic acid in vaginal atrophy. METHODS: A search strategy was developed using the following terms: "Hyaluronic Acid vaginal gel," "vaginal estrogens," "Vaginitis, Atrophic," and "Postmenopause." This strategy was used in major databases such as MEDLINE, EMBASE, Scopus, Cochrane library, Web of Science, Virtual Health Library (BVS), Congress Abstracts, and Gray Literature (Google Scholar and British Library) for studies published until June 2020. OUTCOMES: A systematic review was carried out to assess the results of atrophic vaginitis/vaginal dryness, dyspareunia, vaginal pH, and cell maturation of the studies found by the search strategy. RESULTS: A total of 833 studies were identified, 528 studies were directed for reading titles and abstracts, and 515 were excluded for not meeting the selection criteria. A total of 13 studies were selected for reading the full text. 5 primary studies involving 335 women met the criteria and were included. The studies were published between the years 2011 and 2017. It was not possible to perform meta-analysis owing to the substantial heterogeneity present in the studies. The results presented suggest that treatment with hyaluronic acid, when compared with the use of estrogens, does not present a significant difference in the results obtained for the outcomes: epithelial atrophy, vaginal pH, dyspareunia, and cell maturation. CLINICAL TRANSLATION: Hyaluronic acid appears to be an alternative to non-hormonal treatments for the signs of vaginal atrophy and dyspareunia. STRENGTHS & LIMITATIONS: The analysis of the studies in this systemic review suggests that hyaluronic acid has efficacy similar to vaginal estrogens for the treatment of the signs of vaginal atrophy and dyspareunia. However, the included studies measured the data in different ways, causing the performance of meta-analysis to be impaired. CONCLUSION: The comparisons presented suggest that hyaluronic acid has a profile of efficacy, safety, and tolerability comparable with vaginal estrogens for the treatment of symptoms of vaginal atrophy. It is a possible alternative for women who cannot use hormonal treatment. dos Santos CCM, Uggioni MLR, Colonetti T, et al. Hyaluronic Acid in Postmenopause Vaginal Atrophy: A Systematic Review. J Sex Med 2021;18:156-166.

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial.

OBJECTIVE: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. DESIGN: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. SETTING: KU Leuven, Belgium. SAMPLE: Twenty-four ewes. METHODS: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. MAIN OUTCOME MEASURES: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. RESULTS: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. CONCLUSIONS: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. TWEETABLE ABSTRACT: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

Changes in serum estradiol levels with Estring in postmenopausal women with breast cancer treated with aromatase inhibitors.

BACKGROUND: Anti-estrogen therapy is an effective intervention for preventing reoccurrence of hormone receptor-positive breast cancer in women. However, the side effects of anti-estrogen therapy, including urogenital symptoms, have been reported to cause significant morbidity. There is controversial data, mainly due to small sample sizes, reporting on the safety and efficacy of using vaginal estrogen to treat urogenital symptoms in patients on aromatase inhibitor therapy. METHODS: We proposed a prospective trial to measure the change in blood estradiol levels in postmenopausal women with hormone receptor-positive breast cancer undergoing treatment with aromatase inhibitors when treated with vaginal estrogen preparation, Estring, for their urogenital symptoms. Only 8 prospective patients were enrolled, and the study was amended to include 6 retrospective patients who were treated similarly. Blood estradiol levels were measured at baseline and at week 16 for all patients. RESULTS: The median age for all patients was 55 years, and the majority of them were treated with anastrozole. There was no significant difference between baseline and week 16 estradiol levels (p = 0.81). In addition, patients in the prospective group reported subjective improvement in their vaginal dryness symptoms questionnaires. CONCLUSIONS: The vaginal estrogen preparation, Estring, did not cause persistent elevations in serum estradiol levels and might be a safer option for women with significant urogenital symptoms requiring estrogen therapy. IMPLICATIONS FOR CANCER SURVIVORS: Vaginal estrogen preparation, Estring, might be an option for women with hormone receptor positive breast cancer who have persistent urogenital symptoms.

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

PURPOSE: 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. METHODS: 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 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). RESULTS: Of 101 patients, mean age was 55 years (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). CONCLUSIONS: 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.

Ospemifene in clinical practice for vulvo-vaginal atrophy: results at 3 months of follow-up of use.

OBJECTIVE: To assess the effect of ospemifene 60 mg/day in vulvovaginal atrophy (VVA) in postmenopausal women under conditions of routine clinical practice after 3 months of follow-up. METHODS: The AYSEX study is a Spanish observational, prospective, and unicentric study in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, sexual health, dryness, dyspareunia, quality of life, and satisfaction with treatment were assessed at baseline and after three months using validated scales. RESULTS: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, vaginal health index increased and vaginal pH, dryness, and dyspareunia decreased significantly (p < .0001). A significant improvement was observed in sexual function and quality of life. CONCLUSIONS: This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, and satisfaction with the treatment.

The Efficacy of Vaginal Laser and Other Energy-based Treatments on Genital Symptoms in Postmenopausal Women: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review examined energy-based treatments of the vagina for postmenopausal vaginal symptoms. DATA SOURCES: We performed a systematic review from April 2017 (the end date of our previous review) to April 2020, searching Medline, Embase, and Scopus. METHODS OF STUDY SELECTION: The inclusion criteria were all randomized studies, prospective studies with >10 cases, and retrospective studies with >20 cases published in English or French that assessed change in postmenopausal vaginal symptoms and/or sexual function in women after energy-based vaginal treatments. Meta-analyses were performed on randomized data. TABULATION, INTEGRATION, AND RESULTS: Of the 989 results retrieved, 3 randomized studies, 16 prospective studies, and 7 retrospective studies were included in the review, representing data from 2678 participants. Pooled data from 3 randomized controlled trials show no difference between vaginal laser and topical hormonal treatments for change in vaginal symptoms (-0.14, 95% confidence interval -1.07 to 0.80) or sexual function scores (2.22, 95% confidence interval -0.56 to 5.00). Furthermore, no difference among vaginal laser, topical hormone, and lubricant was demonstrated in sexual function (p = .577). As in our previous review, non-randomized data support energy-based treatments in improving vaginal symptoms, sexual function, and clinician-reported outcomes. No severe adverse events were reported in the included studies. Significant heterogeneity of data arising from differing measures and reported outcomes continues to be an issue, with data remaining low quality, with high risk of bias, and no double-blind or placebo-controlled randomized trials yet reported, although 1 has now completed recruitment. CONCLUSION: There are 3 randomized trials comparing energy-based systems with hormonal treatment, with no clinical difference in these 2 approaches. Although prospective data continue to show promising outcomes, without strong evidence from well-powered, double-blind placebo-controlled trials to determine the efficacy of treatment compared with placebo, the use of energy-based treatments should continue to be undertaken in research studies only, with high-quality studies essentially free from bias (International Prospective Register of Systematic Review registration number: 178346).

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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

INTRODUCTION: Clinical research and management of postmenopausal vaginal symptoms have been limited by the lack of validated measures for assessing symptom impact. AIM: To 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. METHODS: We 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 MEASURE: The 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. RESULTS: Among 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 IMPLICATIONS: Findings 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 & LIMITATIONS: Strengths include the multicenter sample and wide array of measures. Results may not generalize to women with mild symptoms. CONCLUSION: Our 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.

Investigating the effect of vitamin D vaginal suppository on sexual function among postmenopausal women: study protocol for a randomized controlled trial.

BACKGROUND: Menopause is associated with changes in sexual function which are partly due to vaginal atrophy in response to estrogen reduction. Estrogen administration temporarily reduces the symptoms of vaginal dryness, but long-term exposure to this drug is likely to be associated with serious complications. Considering the promising results of previous studies concerning the effect of vitamin D on vaginal dryness, the proposed study will investigate the effect of vitamin D vaginal suppository on the sexual function of postmenopausal women. METHODS: In a randomized, controlled clinical trial, 105 postmenopausal women will be randomly assigned to three groups receiving vitamin D vaginal suppository, placebo vaginal suppository, or control (no intervention). Vitamin D vaginal suppositories contain 1000 units of vitamin D3. The timing of the use of vitamin D vaginal suppositories and placebo suppositories will be every night in the first 2 weeks, and every other night in the following 6 weeks (8 weeks in total). The primary outcome will be the sexual function of participants which will be assessed using the Female Sexual Function Index (FSFI) before and immediately after the intervention, and at 1 and 2 months after the end of the intervention. The side effects of these suppositories will be examined as a secondary consequence of the study. Data will be analyzed using SPSS software version 25. In the case of normal distribution of data, the mean score of sexual function will be compared between the groups using a repeated measurements ANOVA. If statistical analysis leads to significant results, the post-hoc test will be used to determine the differences between the groups. Comparison of demographic and fertility characteristics of the women will be carried out using statistical tests such as chi-squares and t-tests. A significance level of p < .05 will be used for statistical analyses. DISCUSSION: If vitamin D vaginal suppositories improve sexual function among premenopausal women with long-term effects and minimum side effects, the suppositories will be considered a safe complementary and alternative choice for alleviating sexual dysfunction among this group. TRIAL REGISTRATION: IRCT20180704040346N1 at 2018-10-13 prospectively registered.

The effect of oxytocin vaginal gel on vaginal atrophy in postmenopausal women: a randomized controlled trial.

BACKGROUND: Around 90% of postmenopausal women are suffering from vaginal atrophy. This study aimed to evaluate the effect of oxytocin vaginal gel on vaginal atrophy among postmenopausal women. METHODS: This was a randomized controlled trial that was conducted on 96 postmenopausal women who suffered from vaginal atrophy. The inclusion criteria were: literate women, age 40-60, at least 1 year passed from their last menstrual period or the level of FSH > 40 IU, monogamous women with the sexual relationship. Women in the intervention group, requested to use one applicator of 400 IU oxytocin gel per night and women in the placebo group used placebo each night. The subjective symptoms of vaginal atrophy, vaginal PH, maturation index were measured before and after the intervention. RESULTS: The number of superficial cells was increased significantly in the oxytocin group compared to placebo (38.7 ± 7.18 vs. 3.69 ± 2.76, p = 0.0001), while the number of parabasal cells was decreased significantly in the oxytocin compared to placebo after the intervention. The improvement of the maturation index was more dominant in the oxytocin group (increased from 7.76 ± 4.68 to 52.48 ± 7.54) in comparison to the placebo group (increased from 8.58 ± 4.35 to 13.25 ± 5.06). The PH of the vagina decreased significantly in the oxytocin group in comparison to the placebo group (p = 0.0001). After 8 weeks, 88.6 and 7.1% of women in the oxytocin and placebo groups did not show the severe symptoms of vaginal atrophy (p = 0.001). CONCLUSION: The results of this study showed that eight- week intervention with oxytocin vaginal gel (400 IU) could significantly improve the vaginal maturation index, subjective symptoms of vaginal atrophy and reduce the PH of the vagina. Using this medication in women who have a contraindication for hormone therapy is recommended. TRIAL REGISTRATION: IRCT20160602028220N2.