An effective non-hormonal option with high tolerability for mild to moderate symptoms of vaginal dryness associated with menopause.

OBJECTIVES: The efficacy and tolerability of a non-hormonal pessary (that forms an oil-in-water emollient with the vaginal fluid) were assessed for the treatment of symptoms of vaginal dryness associated with menopause. STUDY DESIGN: Seventy-nine postmenopausal women (mean age 60.8 ± 6.5 years) with mild to moderate symptoms of vaginal dryness (including dyspareunia) were enrolled in this open-label, prospective, post-market clinical follow-up trial, conducted in 2022 by one research center in Germany. The investigational pessary was applied for the first 7 days once daily and the subsequent 31 days twice a week, at bedtime. A treatment-free period of 6 days completed the trial. MAIN OUTCOME MEASURES: During the trial, participants filled out questionnaires that enabled the calculation of a total severity score for subjective symptoms of atrophy-related vaginal dryness and impairment of daily as well as sexual life. Furthermore, vaginal health index and safety were studied. RESULTS: A rapid and significant reduction in the severity scores for symptoms was observed over the 38-day course of treatment and beyond. Quality of life assessed by DIVA (day-to-day impact of vaginal aging) questionnaire, dyspareunia and vaginal health index also clearly improved. The tolerability was mainly rated as "good to very good" by the investigator and 94.9 % of participants. The vast majority were very satisfied with the simple and pleasant handling. No serious adverse events occurred. CONCLUSION: Overall, the presented data suggest that the investigated non-hormonal pessary is an effective and well tolerated treatment option for vaginal symptoms associated with dryness, thus improving quality of life for women, even those who are sexually active. CLINICALTRIALS: gov identifier NCT05211505.

The effects of a real-time temperature monitoring non-ablative monopolar radiofrequency technology on vulvovaginal atrophy symptoms in postmenopausal Chinese women.

BACKGROUND: Vulvovaginal atrophy (VVA) includes a wide range of conditions affecting the reproductive and urinary systems, often requiring careful evaluation and management for optimal health. AIMS: This study aims to evaluate the symptom management effects of a real time temperature-monitored non-ablative RF device for the treatment of postmenopausal Chinese women with VVA symptoms. METHODS: This pilot study involved 24 postmenopausal Chinese women with one or more VVA symptoms, who wished to remain sexually active. VHIS, VAS, and FSFI were used to track and evaluate various aspects of the patient's condition. Analyses were conducted at the end of the study to verify the statistical significance of the treatment's results. RESULTS: All patients reported substantial, statistically significant, improvements on every VVA symptom tracked. Approximately 80% of the patients reported total symptom reversal at 12-week post-treatment follow-up. CONCLUSION: This pilot study demonstrated that non-ablative, monopolar RF technology equipped with real time temperature monitoring is feasible and safe in the treatment of postmenopausal women with VVA symptoms, and efficacious at up to 12 weeks post-treatment.

Vaginal dryness: a review of current understanding and management strategies.

The issue of vaginal dryness in genitourinary syndrome of menopause (GSM) and its pervasive impact on women's quality of life is often overlooked. Extensive surveys conducted worldwide reveal limited understanding of vaginal dryness among public and health-care providers. Physician knowledge on menopause medicine varies globally, highlighting the need for standardized training. Effective communication between physicians and patients plays a crucial role in diagnosing and treating GSM symptoms. There are multiple treatment options to improve vaginal lubrication, including hormonal and non-hormonal therapies, along with lifestyle modifications. Tailoring treatments to individual patient preferences is crucial for compliance. Overall, GSM is multifaceted, from the prevalence of vaginal dryness to the nuances of treatment preferences. The urgency of widespread education and awareness of this matter must be underscored to meet the aim of enhancing the well-being and quality of life for women.

Effect of topical 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser pretreatment for vaginal condyloma acuminate.

BACKGROUND: Condyloma acuminatum (CA) of the vagina is a sexually transmitted disease due to infection by human papilloma virus (HPV). The treatment efficacy of the conventional methods for vaginal CA is often unsatisfactory with a high recurrence rate. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) combined with CO2 laser pretreatment is a feasible approach for vaginal CA, but the effectiveness and safety need further evaluation. METHODS: This study enrolled 15 patients with vaginal CA. All patients underwent CO2 laser ablation and then ALA-PDT for two or three cycles. The clinical efficacy and side effects were evaluated and analyzed during the treatment and 6 months after the treatment. RESULTS: The wart lesions in 4 cases (26.7 %) disappeared after the first treatment. The wart lesions in 5 cases (33.3 %) disappeared after the second treatment. And 6 cases (40 %) needed three treatment cycles before the lesions disappeared completely. The complete response (CR) rate was 93.3 % (14/15) at 2 weeks after three treatment cycles. There were 5 cases (83.3 %) which have complete remission after 2 treatments in warts diameter <1 cm group. There were only 4 cases (44.4 %) which have complete remission after 2 treatments in diameter>1 cm group. All patients had CR without reoccurrence at 6 months after treatment. The side effects mainly included a mild or moderate burning or stinging sensation (26.7 %). There were no infection, ulcers and scars after treatment. CONCLUSION: Topical 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser pretreatment is a safe and effective treatment for vaginal CA.

Randomized trial: treatment of genitourinary syndrome of menopause using radiofrequency.

OBJECTIVE: A randomized controlled study was conducted to evaluate the safety and efficacy of radiofrequency treatment in postmenopausal women not willing to use or presenting a contraindication for menopause hormone therapy (MHT) and suffering from genitourinary syndrome of menopause (GSM). METHODS: A prospective randomized open study evaluated the effect of radiofrequency treatment versus a gel (control group) in postmenopausal women suffering from GSM. Patients were assessed at baseline and after 10-12 weeks of treatment for severity of vulvovaginal atrophy, dyspareunia, pH, vaginal smear maturation index, Vaginal Health Index and Female Sexual Function Index. The difference at baseline and after 10-12 weeks of treatment and the difference in improvement were tested between groups by a two-sample t-test and the Mann-Whitney test. RESULTS: Due to the COVID-19 pandemic, we were only able to treat 48 patients (24 patients using radiofrequency and 24 patients using a gel). Globally, at the end of the study, there were no differences in changes of the measured outcomes between the group of women treated with radiofrequency and the control group. CONCLUSION: Radiofrequency treatment was found to be safe, but was not superior to a gel, although the study lacked power. The study was registered at ClinicalTrials.gov (NCT03857893).

Applicability of vaginal energy-based devices in urogynecology: evidence and controversy.

OBJECTIVE: This study aimed to analyze the evidence and controversies about the use of vaginal energy-based devices (laser and radiofrequency) for treatment of genitourinary syndrome of menopause, recurrent urinary tract infection, urinary incontinence, and genital prolapse through a literature review. METHODS: A search of literature databases (PubMed, Medline) was performed for publications in December 2022. Keywords included genitourinary syndrome of menopause, vaginal laxity, vaginal/vulvovaginal atrophy, urinary tract infection, urgency incontinence, frequency, urgency, stress urinary incontinence, genital prolapses AND energy-based devices, AND vaginal laser, AND vaginal radiofrequency, AND CO2 laser, AND Er:YAG laser. Publications in English from the last 7 years were reviewed and selected by the authors. RESULTS: The literature regarding vaginal energy-based devices in the treatment of urogynecological conditions is primarily limited to prospective case series with small numbers and short-term follow-up. Most of these studies showed favorable results, improvement of symptoms with low risk, or no mention of serious adverse events. Consensus statement documents from major medical societies suggest caution in recommending these therapies in clinical practice until more relevant data from well-designed studies become available. CONCLUSION: The potential of the vaginal laser and radiofrequency as a therapeutic arsenal for the evaluated urogynecological conditions is great, but qualified research must be done to prove their efficacy and long-term safety, define application protocols, and recommend the use of these technologies in clinical practice.

Different local estrogen therapies for a tailored approach to GSM.

Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.

The role of microbiota in the management of genitourinary syndrome of menopause.

It is estimated that the 25-50% of women who are reaching menopause every year report symptoms related to the genitourinary syndrome of menopause (GSM). The symptoms are not due simply to lack of estrogen. One possible contributing cause of symptoms is the vaginal microbiota. The vaginal microbiota is a dynamic entity and plays a critical role in the pathogenic interplay of postmenopausal changes. Treatment of this syndrome depends on the severity and type of the symptoms and on the preferences and expectations of women. As there are many treatment options, therapy should be individualized. While new evidence on the role of Lactobacilli in premenopause is emerging, the role of Lactobacilli is still unclear in GSM and the impact of microbiota on vaginal health remains conflictual. However, some reports show promising data on the effect of probiotic therapy in menopause. In the literature there are few studies and small population samples on the role of an exclusive therapy with Lactobacilli and further data will be mandatory. Studies involving large numbers of patients and different intervention periods will be necessary to obtain evidence of the preventive and curative role of vaginal probiotics.

An online survey on coping methods for genitourinary syndrome of menopause, including vulvovaginal atrophy, among Japanese women and their satisfaction levels.

BACKGROUND: This study aimed to explore the current situation and existing issues regarding the management of vulvovaginal atrophy (VVA) or the genitourinary syndrome of menopause (GSM). A nationwide web-based questionnaire survey was conducted among 1,031 Japanese women aged 40 years or older. MATERIALS AND METHODS: Eligible women were asked to complete a questionnaire about how they dealt with their symptoms and how satisfied they were with their coping methods. RESULTS: Of those highly conscious of their GSM symptoms (n = 208; 20.2%), 158 had sought medical consultation (15.3%), with only 15 currently continuing to seek consultation (11.5%). Of the specialties consulted, gynecology was the most frequently consulted (55%). Furthermore, those unwilling to seek medical consultation despite their symptoms accounted for the greatest proportion (n = 359; 34.8%), with 42 (23.9%) having never sought consultation. Topical agents, e.g., steroid hormone ointments/creams, were the most frequent treatments provided by the clinics (n = 71; 40.3%), followed by oral and vaginal estrogens (n = 27; 15.5%), suggesting that estrogen therapy was not the first choice of treatment at the clinics. While 65% of patients treated at the clinics reported satisfaction with the treatments, this was inconsistent with the fact that many were reported to have remained untreated and very few continued with treatment. CONCLUSIONS: Survey results suggest that GSM, including VVA, remains underdiagnosed and undertreated in Japan. Medical professionals should deepen their understanding of GSM and raise their level of care to select the appropriate treatment for the condition.

Complex vulvar and vaginal disease in menopause.

PURPOSE OF REVIEW: Menopause is a time of vulvar and vaginal changes that are physiologic and are often symptomatic. These changes can impact up to 50% of women in menopause. There are also several vulvar dermatoses that are more common after menopause and should be recognized early to allow for symptomatic treatment. Some of these conditions can lead to squamous cell carcinoma over time, and early recognition and appropriate treatment reduce this risk. Treatment for women with symptomatic vulvar and vaginal conditions is important for maintaining the quality of life. RECENT FINDINGS: There are multiple review articles, small case series, and small comparative trials, but definitive trials are unavailable for most of these conditions. SUMMARY: Current research on pathophysiology and treatment is limited to all of these conditions, and more focus on these life-altering conditions is warranted.

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study.

To evaluate safety and effectiveness of therapeutic ultrasound for treatment of postmenopausal vaginal dryness. In a pilot study, postmenopausal women with self-reported vaginal dryness were randomized (1:1) to double-blind ultrasound treatment (n = 21) or sham (n = 21) for 12 weeks. Primary effectiveness endpoint was change from baseline to week 12 in Vaginal Assessment Scale symptoms (dryness, soreness, irritation, dyspareunia). Secondary effectiveness endpoint was scoring of clinician-reported Vaginal Health Index (elasticity, fluid, pH, mucosa, moisture). After 12 weeks, participants received open-label ultrasound treatment to 1 year. Safety endpoint was treatment-emergent adverse events. In the modified intent-to-treat population, women showed (mean ± standard error) reduction in Vaginal Assessment Scale with ultrasound treatment versus sham (n = 15, −0.5 ± 0.2 vs n = 15, −0.4 ± 0.3; P = 0.9) and improved Vaginal Health Index (n = 9, 2.7 ± 0.9 vs n = 9, 0.6 ± 1.4; P = 0.3). In the per-protocol analysis population, ultrasound treatment (n = 9) versus sham (n = 8) significantly reduced symptoms score (−0.6 ± 0.3 vs −0.0 ± 0.4; P = 0.05) and significantly improved Vaginal Health Index (2.7 ± 0.9 vs −0.4 ± 1.2; P = 0.03). Improvement in effectiveness endpoints were seen at 1 year compared with baseline. There were no differences in treatment-emergent adverse events between ultrasound treatment versus sham and no serious adverse events. Home-use ultrasound was safe and effective for treating vaginal dryness after 12 weeks. Effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormonal treatment option for postmenopausal women with vulvovaginal atrophy.

Vaginal oxygen plus hyaluronic acid on genito-urinary symptoms of breast cancer survivors.

OBJECTIVES: This study aimed to evaluate the efficacy of vaginal oxygen and hyaluronic acid on genito-urinary symptoms of breast cancer survivors. METHODS: Patients were enrolled at the Menopause Outpatient Clinic of a university hospital. Breast cancer patients in a stable relationship, suffering from vaginal atrophy (VA) consequent to hypoestrogenism, were included. Natural oxygen was introduced into the vagina for 15 min, coupled in the last 5 min with a 2% solution of hyaluronic acid. Treatment was repeated five times, every 15 days. RESULTS: Out of the 40 breast cancer patients enrolled, 65% had no sexual intercourse due to pain. During treatment, the Vaginal Health Index Score gradually improved from 9.5 ± 2.2 to 16.8 ± 2.8 (p < 0.001), the visual analog scale score for dyspareunia decreased from 8.9 ± 1.3 to 3.4 ± 2.1 (p < 0.001) and the Female Sexual Function Index increased from 8.6 ± 6.3 to 15.2 ± 8.1 (p < 0.001). At the end of treatment, only 15% women (p = 0.001 vs. pretreatment) had no intercourse due to pain. Benefits remained 30 days after last treatment. CONCLUSION: Vaginal oxygenation coupled with hyaluronic acid every 15 days improves VA, sexuality and urinary symptoms of breast cancer patients. Beside data confirmation, additional studies are needed to determine the best interval between treatments, the optimal length of treatment and the long-term duration of the benefits.

Sexual function analysis and clitoral vascularization in postmenopausal women with genitourinary syndrome treated with ospemifene.

BACKGROUND: The aim of this study was to evaluate the efficacy of ospemifene in the Vaginal Health Index (VHI), in the vulvovaginal vascular perfusion, and to assess its impact on quality of life and sexual function. METHODS: Among 52 eligible patients, 43 consecutive postmenopausal patients affected by vulvo-vaginal atrophy (VVA), or genitourinary syndrome (GSM) were evaluated. VVA evaluation and ultrasound of the vulvo-vaginal vascularization by sampling the Pulsatility Index (PI) of clitoris dorsal artery were performed before and after 3 months-treatment with ospemifene. The 36-Item Short Form Survey (SF-36) for the quality-of-life assessment before and after 3 months were available for all women; instead, Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires for the sexual function evaluation were performed for sexually active women in the study. The Patient Impression of Global Improvement (PGI-I) after 3 months of treatment was also calculated. RESULTS: The number of sexually active women significantly increased after 3 months (26 [60.46%] vs. 35 [81.39%]; P=0.01). The mean number of intercourses during the treatment increased (12.87±3.43 vs. 15.79±3.12, P=0.03). The PI of clitoris dorsal artery has significantly changed before and after treatment respectively (PI [1.69±0.42 vs. 1.28±0.45, P=0.001] RI [0.74±0.11 vs. 0.54±0.15, P=0.001]). The FSFI, FSDS and SF-36 Questionnaires scores showed a significant improvement after 3 months. VHI and PI were the independent factors of a lower FSFI after 3 months of treatment at multivariate analysis. CONCLUSIONS: Ospemifene improve the VHI and vulvovaginal vascular perfusion demonstrating a positive impact on sexual function and quality of life.

Effect of oestriol gel on dyspareunia in postmenopausal women in 2 weeks of treatment: a pilot study.

This brief report evaluates the early effect of ultra-low dose 0.005% oestriol vaginal gel on dyspareunia in postmenopausal women within the first 2 weeks of treatment. This was a prospective and multicentre single-arm pilot study and the effect of the treatment on dyspareunia was evaluated by using a diary. In total 23 women and 150 coitus were studied. 8 coitus were painless in the first week and 42 during the second week (p < .0001). A reduction in pain from the baseline was seen in 116 (77.3%) out of the 150 coitus. 0.005% oestriol vaginal gel produced a rapid and progressive improvement in dyspareunia from the very first days of treatment in postmenopausal women.IMPACT STATEMENTWhat is already known on this subject? Local oestrogen therapy has shown efficacy in the treatment of genitourinary syndrome of menopause (GSM) and dyspareunia when used for a duration of greater than 3 weeks.What do the results of this study add? This study shows that the use of oestriol gel produces clinical effects from the beginning of its use, decreasing dyspareunia in postmenopausal women within just 14 days of daily use.What are the implications of these findings for clinical practice and/or further research? In cases of dyspareunia in relation to menopause, therapy with local oestrogens, in our case oestriol gel, produces an improvement from the beginning of its use. This information is clinically relevant when evaluating therapeutic options.

New Innovations for the Treatment of Vulvovaginal Atrophy: An Up-to-Date Review.

Vulvovaginal atrophy (VVA) is a chronic progressive disease involving the female genital apparatus and lower urinary tract. This condition is related to hypoestrogenism consequent to menopause onset but is also due to the hormonal decrease after adjuvant therapy for patients affected by breast cancer. Considering the high prevalence of VVA and the expected growth of this condition due to the increase in the average age of the female population, it is easy to understand its significant social impact. VVA causes uncomfortable disorders, such as vaginal dryness, itching, burning, and dyspareunia, and requires constant treatment, on cessation of which symptoms tend to reappear. The currently available therapies include vaginal lubricants and moisturizers, vaginal estrogens and dehydroepiandrosterone (DHEA), systemic hormone therapy, and Ospemifene. Considering, however, that such therapies have some problems that include contraindications, ineffectiveness, and low compliance, finding an innovative, effective, and safe treatment is crucial. The present data suggest great efficacy and safety of a vaginal laser in the treatment of genital symptoms and improvement in sexual function in patients affected by VVA. The beneficial effect tends to be sustained over the long-term, and no serious adverse events have been identified. The aim of this review is to report up-to-date efficacy and safety data of laser energy devices, in particular the microablative fractional carbon dioxide laser and the non-ablative photothermal Erbium-YAG laser.

Graft-versus-host disease in the female genital tract: a prospective cohort study.

BACKGROUND: Graft-versus-host disease (GVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD in the female genital tract can cause sinusorrhagia, dyspareunia, synechia, and even complete vagina occlusion. PURPOSE: This prospective study aimed to evaluate the clinical characteristics and effects of preventive and prompt treatment for genital GVHD in females undergoing HSCT (n = 40). RESULTS: Genital GVHD was diagnosed in 11 of 40 patients (27.5%), and the most common complaint was vaginal dryness (54.6%). The majority of patients (63.6%) presented mild genital GVHD (clinical score 1), with interlabial fissures and lichen-like lesions, while a minority of patients (9.1%) presented advanced genital GVHD (clinical score 3) with the fusion of the small and large lips. The median time of onset of genital GVHD signs was 10 months after HSCT, concomitant with GVHD in the skin and oral cavity. Personalized and topical therapy was effective in most cases (81.8%), and no patient required surgical intervention. CONCLUSION: We confirmed that female genital GVHD affects approximately one-third of females undergoing HSCT, highlighting the importance of periodic gynecological monitoring for early detection and treatment to improve care for these females.

A new approach to regenerative medicine in gynecology.

OBJECTIVE: To evaluate the efficacy of the injection of microfragmented adipose tissue in the treatment of women with genitourinary syndrome of menopause (GSM). METHODS: This observational cohort study included 12 women who received one session of multiple injections of microfragmented adipose tissue using the SEFFIGYN™ medical device. Symptoms such as burning, itching, dryness, pain on penetration, pain during deep intercourse, and pain on urination were assessed before the patient's treatment (T0), after 15 days (T15), and after 5 months (5Mo) using the Numerical Rating Scale (NRS). RESULTS: An improvement of vulvar trophism was clinically evident already 2 weeks after treatment; all symptoms were notably attenuated compared with the initial visit, as demonstrated by statistically significant reductions of the NRS scores (P = 0.003 for itching, P = 0.008 for pain on urination, and P < 0.001 for the other symptoms, Sign test). Moreover, all symptoms continued to improve over time. All patients reported a positive change in their quality of life and a resumption of sexual life. CONCLUSION: The use of microfragmented adipose tissue in GSM is promising. Nevertheless, more studies will be fundamental to exclude a potential placebo effect and better understand the underlying molecular mechanism of action.

Intravaginal nonablative radiofrequency in the treatment of genitourinary syndrome of menopause symptoms: a single-arm pilot study.

BACKGROUND: Genitourinary syndrome of menopause (GSM) involves vaginal dryness (VD), pain during sexual activity (SAPain), vaginal itching (VI), burning, pain, and symptoms in the urinary organs. Non-ablative radiofrequency (RF) is a type of current with electromagnetic waves with a thermal effect that generates an acute inflammatory process with consequent neocolagenesis and neoelastogenesis. We aimed to describe the clinical response to VD, SAPain, vaginal laxity (VL), VI, burning sensation, pain in the vaginal opening, urinary incontinence, sexual dysfunction, cytological changes, and adverse effects of non-ablative RF in patients with GSM. METHODS: This single-arm pilot study included 11 women diagnosed with GSM with established menopause. Patients with hormone replacement initiation for six months, who used a pacemaker, or had metals in the pelvic region, were excluded. Subjective measures (numeric rating scale of symptoms, Vaginal Health Index-VHI) and objective measures (vaginal maturation index-VMI, vaginal pH, sexual function by the FSFI, and urinary function by the ICIQ-SF) were used. A Likert scale measures the degree of satisfaction with the treatment. Five sessions of monopolar non-ablative RF (41°C) were performed with an interval of one week between each application. The entire evaluation was performed before treatment (T0), one month (T1), and three months (T2) after treatment. Adverse effects were assessed during treatment and at T1 and T2. RESULTS: The symptoms and/or signs were reduced after treatment in most patients (T1/T2, respectively): VD 90.9%/81.8%, SAPain 83.3%/66.7, VL 100%/100%, VI 100%/100%, burning 75%/87.5%, pain 75%/75%, and VHI 90.9%/81.9%. Most patients did not show changes in VMI (54.5%) and pH (63.6%) at T1, but there was an improvement in VMI in most patients (54.5%) at T2. Nine patients were satisfied, and two were very satisfied at T1. The treatment was well tolerated, and no adverse effects were observed. There was an improvement in sexual function (72.7%) and urinary function (66.7% in T1 and 83.3% in T2). CONCLUSION: Intravaginal RF reduced the clinical symptoms of GSM in most patients, especially during T1, and women reported satisfaction with treatment. The technique showed no adverse effects, and there were positive effects on sexual and urinary function. Trial registration This research was registered at clinicaltrial.gov (NCT03506594) and complete registration date was posted on April 24, 2018.

A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial.

BACKGROUND: Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women. METHODS AND FINDINGS: This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020. Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention. CONCLUSIONS: In this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079388.

Microablative fractional radiofrequency for the genitourinary syndrome of menopause: protocol of randomised controlled trial.

INTRODUCTION: Menopause is a physiological and progressive phenomenon secondary to decreased ovarian follicular reserve. These changes have consequences: vaginal dryness, dyspareunia, discomfort, burning and irritation, vulvovaginal pruritus, dysuria and increased frequency of genitourinary infections. The therapy more suitable for vaginal symptoms in postmenopause yet is the use of a topical hormone. However, the prescription of topical oestrogens should also be avoided in women with a history of breast cancer, oestrogen-sensitive tumours and thromboembolism, emphasising the necessity of alternative treatments. Recently, physical methods, such as laser and radiofrequency (RF), in their non-ablative, ablative and microablative forms have been used in the vaginal mucosa to promote neocolagenesis and neoelastogenesis. This randomised study aims to compare the efficiency of microablative fractional RF (MAFRF) treatment with vaginal oestrogens and no treatment. METHODS AND ANALYSES: This randomised, controlled clinical intervention trial with an open label design comparing the treatment of MAFRF with vaginal oestrogens and no treatment. Four important moments were considered to evaluate treatment results (T0, T1, T2 and T3). The primary outcome includes vulvovaginal atrophy (vaginal pain, burning, itching, dryness, dyspareunia and dysuria), and the secondary outcomes will be sexual function, vaginal health (epithelial integrity, vaginal elasticity, moisture, fluid volume and vaginal pH) and quality of life. ETHICS AND DISSEMINATION: Due to the nature of the study, we obtained approval from the ethics committee. All participants must sign an informed consent form before randomisation. The results of this study will be published in peer-reviewed journals. The data collected will also be available in a public repository of data. TRIAL REGISTRATION NUMBER: RBR-94DX93.