The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer.

Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions-data-dependent acquisition (DDA) and data-independent acquisition (DIA)-on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM.

Image-guided cancer surgery: a narrative review on imaging modalities and emerging nanotechnology strategies.

Surgical resection is the cornerstone of solid tumour treatment. Current techniques for evaluating margin statuses, such as frozen section, imprint cytology, and intraoperative ultrasound, are helpful. However, an intraoperative assessment of tumour margins that is accurate and safe is clinically necessary. Positive surgical margins (PSM) have a well-documented negative effect on treatment outcomes and survival. As a result, surgical tumour imaging methods are now a practical method for reducing PSM rates and improving the efficiency of debulking surgery. Because of their unique characteristics, nanoparticles can function as contrast agents in image-guided surgery. While most image-guided surgical applications utilizing nanotechnology are now in the preclinical stage, some are beginning to reach the clinical phase. Here, we list the various imaging techniques used in image-guided surgery, such as optical imaging, ultrasound, computed tomography, magnetic resonance imaging, nuclear medicine imaging, and the most current developments in the potential of nanotechnology to detect surgical malignancies. In the coming years, we will see the evolution of nanoparticles tailored to specific tumour types and the introduction of surgical equipment to improve resection accuracy. Although the promise of nanotechnology for producing exogenous molecular contrast agents has been clearly demonstrated, much work remains to be done to put it into practice.

Phospho-DIGE Identified Phosphoproteins Involved in Pathways Related to Tumour Growth in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic malignancy of the endometrium. This study focuses on EC and normal endometrium phosphoproteome to identify differentially phosphorylated proteins involved in tumorigenic signalling pathways which induce cancer growth. We obtained tissue samples from 8 types I EC at tumour stage 1 and 8 normal endometria. We analyzed the phosphoproteome by two-dimensional differential gel electrophoresis (2D-DIGE), combined with immobilized metal affinity chromatography (IMAC) and mass spectrometry for protein and phosphopeptide identification. Quantities of 34 phosphoproteins enriched by the IMAC approach were significantly different in the EC compared to the endometrium. Validation using Western blotting analysis on 13 patients with type I EC at tumour stage 1 and 13 endometria samples confirmed the altered abundance of HBB, CKB, LDHB, and HSPB1. Three EC samples were used for in-depth identification of phosphoproteins by LC-MS/MS analysis. Bioinformatic analysis revealed several tumorigenic signalling pathways. Our study highlights the involvement of the phosphoproteome in EC tumour growth. Further studies are needed to understand the role of phosphorylation in EC. Our data shed light on mechanisms that still need to be ascertained but could open the path to a new class of drugs that could hinder EC growth.

A Multi-Omics Approach Revealed Common Dysregulated Pathways in Type One and Type Two Endometrial Cancers.

Endometrial cancer (EC) is the most frequent gynecologic cancer in postmenopausal women. Pathogenetic mechanisms that are related to the onset and progression of the disease are largely still unknown. A multi-omics strategy can help identify altered pathways that could be targeted for improving therapeutical approaches. In this study we used a multi-omics approach on four EC cell lines for the identification of common dysregulated pathways in type 1 and 2 ECs. We analyzed proteomics and metabolomics of AN3CA, HEC1A, KLE and ISHIKAWA cell lines by mass spectrometry. The bioinformatic analysis identified 22 common pathways that are in common with both types of EC. In addition, we identified five proteins and 13 metabolites common to both types of EC. Western blotting analysis on 10 patients with type 1 and type 2 EC and 10 endometria samples confirmed the altered abundance of NPEPPS. Our multi-omics analysis identified dysregulated proteins and metabolites involved in EC tumor growth. Further studies are needed to understand the role of these molecules in EC. Our data can shed light on common pathways to better understand the mechanisms involved in the development and growth of EC, especially for the development of new therapies.

Hysteroscopic Treatment of Cervical Pregnancy: A Scoping Review of the Literature.

OBJECTIVE: Many therapies have been proposed for cervical pregnancy (CP) treatment; however, there is no consensus on the best practice to adopt, mainly owing to the rarity of this condition and the lack of randomized controlled trials. Therefore, there are no clinical practice guidelines for the management of this patient set. We presented an English literature review about the hysteroscopic management of CP. DATA SOURCES: The literature review was performed according to the Preferred Reporting Items for Scoping Reviews. The search strategy aimed at identifying cases from the first patients tracked down to those diagnosed in May of 2021. We searched in PubMed, Scopus, Google Scholar, and MEDLINE databases. Mesh terms used included "Cervical Pregnancy," "Hysteroscopy," "Ectopic pregnancy," and "Resectoscopy." METHOD OF STUDY SELECTION: Case reports of randomized controlled trials, prospective controlled studies, prospective cohort studies, retrospective studies, case series, and case reports were considered eligible. Review, Letters to the Editor, and abstracts accepted at conferences were ruled out. TABULATION, INTEGRATION, AND RESULTS: We found a total of 3572 articles in all analyzed databases. A total of 2480 articles viewed were duplicated and therefore ruled out. After screening and excluding nonpertinent articles, 109 were assessed for eligibility, and 19 were included in the analysis. All articles were single case reports, small case series with no criteria selection, randomization, or study planning. We classified them as follows: cases treated with 10 mm resectoscope, with or without pretreatments of previous CP hysteroscopic approach, and cases resolved with 5 mm hysteroscopy, with or without pretreatments of previous CP hysteroscopic approach. CONCLUSION: The hysteroscopic method represents a feasible and safe approach to the CP treatment, although there are still some aspects to be clarified, such as the pretreatment need and the instruments' type and sizes based on the beta-subunit of human chorionic gonadotropin, pregnancy age, and dimension.

Gel-Based Proteomic Identification of Suprabasin as a Potential New Candidate Biomarker in Endometrial Cancer.

Endometrial cancer (EC) is the most frequent gynaecologic cancer in postmenopausal women. We used 2D-DIGE and mass spectrometry to identify candidate biomarkers in endometrial cancer, analysing the serum protein contents of 10 patients versus 10 control subjects. Using gel-based proteomics, we identified 24 candidate biomarkers, considering only spots with a fold change in volume percentage ≥ 1.5 or intensity change ≤ 0.6, which were significantly different between cases and controls (p < 0.05). We used Western blotting analysis both in the serum and tissue of 43 patients for data validation. Among the identified proteins, we selected Suprabasin (SBSN), an oncogene previously associated with poor prognosis in different cancers. SBSN principal isoforms were subjected to Western blotting analysis in serum and surgery-excised tissue: both isoforms were downregulated in the tissue. However, in serum, isoform 1 was upregulated, while isoform 2 was downregulated. Data-mining on the TCGA and GTEx projects, using the GEPIA2.0 interface, indicated a diminished SBSN expression in the Uterine Corpus Endometrial Cancer (UCEC) database compared to normal tissue, confirming proteomic results. These results suggest that SBSN, specifically isoform 2, in tissue or serum, could be a potential novel biomarker in endometrial cancer.

Laparoscopic monolateral suspension for vaginal vault prolapse: a report of an exit surgical strategy during sacralcolpopexy.

BACKGROUND: Vaginal vault prolapse is the most frequent long-term complication in patients undergoing hysterectomy and sacralcolpopexy is considered the gold standard. We report our surgical strategy maintaining single-arm mesh when the sacral promontory is not accessible to fix the mesh for an unknown sacral osteophytosis during a laparoscopic sacralcolpopexy. This is significant because, to our knowledge, the bone variant as a procedure limiting factor has never been described before. This opens new horizons for the sacralcolpopexy surgery, because it becomes necessary to know of a valid surgical alternative with mesh maintenance if this complication occurs again or to perform an assessment of the accessibility of the sacral promontory immediately after its dissection. CASE PRESENTATION: We present a case of a 75-year-old woman with recurrence of vaginal vault prolapse. A laparoscopic sacralcolpopexy was recommended. During surgery, we found that the procedure was not feasible due to the presence of an unknown osteophytosis of the sacrum which prevented the fixing of the mesh to the sacral promontory. We decided to proceed with a single-arm lateral suspension by using a modified approach of the original technique, maintaining the mesh originally shaped for the sacral colpopexy. At follow-up, the vaginal vault is well suspended. CONCLUSION: This exit strategy may represent a valid surgical alternative when laparoscopic sacral colpopexy is not possible for anatomical variants, allowing to keep the laparoscopic approach using mesh. To our knowledge, cases in which the anatomical bone variant prevented access to the sacral promontory have never been described in the literature, as bone evaluation has never been considered a limiting element of this procedure.

Total Hysteroscopic Treatment of Cervical Pregnancy: The 2-step Technique.

STUDY OBJECTIVE: To evaluate the efficacy of total surgical treatment of ectopic cervical pregnancy [1] with a minimally invasive approach performed by hysteroscopy [2]. DESIGN: Step-by-step video demonstration of the surgical technique using 5 mm hysteroscopy followed by 10 mm resectoscopy. SETTING: A research and university hospital (IRCCS Burlo Garofolo, Trieste, Italy). PATIENTS: A 41-year-old woman with an ultrasound diagnosis of ectopic cervical pregnancy at 6 + 6 weeks of gestation with a beta human chorionic gonadotropin serum level of 55.951 mUI/mL. INTERVENTIONS: We performed a 2-step technique using 5- and 10-mm hysteroscopy (Video 1). During the first step, a 5-mm Bettocchi hysteroscope (Karl Storz, Tuttlingen, Germany) with a 5F bipolar electrode Versapoint Twizzle (Gynecare, Menlo Park, CA) was used. In this phase, the gestational sac was identified in order to confirm the diagnosis and its site of implantation. Later, the gestational sac was opened, and the pregnancy was terminated by cord section under an embryoscopic view (Fig. 1). Finally, a partial vessel coagulation was performed. Afterward, the cervix was dilated, and a resectoscopy was performed. During the second step, a 10-mm Gynecare resectoscope with the bipolar Gynecare Versapoint was used and the gestational sac with the embryo was removed; subsequently, a complete chorial villi resection was achieved. At last, a coagulation of bleeding vessels on the implantation site in order to control the hemostasis was performed (Fig. 2). MEASUREMENTS AND MAIN RESULTS: The study was approved by the institutional review board. The patient was discharged 24 hours after the procedure with an uneventful postoperative course, and the beta human chorionic gonadotropin serum level became negative in 20 days. After 40 days, the ultrasound cervical findings were regular, whereas office hysteroscopy showed the implantation site scar. After 5 months, the patient was pregnant with regular intrauterine implantation (Fig. 3). CONCLUSION: The total hysteroscopic approach with a 2-step technique offers an effective, safe, and minimally invasive surgical treatment to ectopic cervical pregnancy. Considering that our method, in contrast with the recent literature [3-5], is performed without any medical treatment, we reported for the first time an approach, that deserve more clinical data to confirm its effectiveness.

Interstitial Fluid in Gynecologic Tumors and Its Possible Application in the Clinical Practice.

Gynecologic cancers are an important cause of worldwide mortality. The interstitium consists of solid and fluid phases, situated between the blood vessels and cells. The interstitial fluid (IF), or fluid phase, is an extracellular fluid bathing and surrounding the tissue cells. The TIF (tumor interstitial fluid) is a dynamic fluid rich in lipids, proteins and enzyme-derived substances. The molecules found in the IF may be associated with pathological changes in tissues leading to cancer growth and metastatization. Proteomic techniques have allowed an extensive study of the composition of the TIF as a source of biomarkers for gynecologic cancers. In our review, we analyze the composition of the TIF, its formation process, the sampling methods, the consequences of its accumulation and the proteomic analyses performed, that make TIF valuable for monitoring different types of cancers.

A Psychological Point of View on Endometriosis and Quality of Life: A Narrative Review.

Endometriosis is a chronic gynecological disorder with a multifactorial etiology that has not yet been fully elucidated. What is known, however, are the pathological tissue dynamics that lead to the complex symptoms that women suffer from. The known symptoms are mainly fertility problems and pain. Both dimensions have an impact that varies from case to case, but that is certainly decisive concerning a woman's health, specifically by affecting the overall quality of life (QoL). In this publication, we will deal with the descriptive aspects of endometriosis's pathology and then present a review of the aspects impacting QoL and their psycho-social consequences. Finally, the experience of pain in the context of the mind-brain-body relationship will be discussed, describing the complexity of this dimension and emphasizing the importance of a multi-professional approach that considers the relevance of the contribution that a psychotherapy intervention based on up-to-date neurobiological models can make for women with endometriosis. A review of the literature and current knowledge on the neural and psychological aspects of pain lead to the conclusion that it is of the utmost importance to provide informed psychological support, alongside medical treatments and sexual counseling, to patients with endometriosis.

The Women4Health cohort: a unique cohort to study women-specific mechanisms of cardio-metabolic regulation.

Aims: Epidemiological research has shown relevant differences between sexes in clinical manifestations, severity, and progression of cardiovascular and metabolic disorders. To date, the mechanisms underlying these differences remain unknown. Given the rising incidence of such diseases, gender-specific research on established and emerging risk factors, such as dysfunction of glycaemic and/or lipid metabolism, of sex hormones and of gut microbiome, is of paramount importance. The relationships between sex hormones, gut microbiome, and host glycaemic and/or lipid metabolism are largely unknown even in the homoeostasis status. Yet this knowledge gap would be pivotal to pinpoint to key mechanisms that are likely to be disrupted in disease context. Methods and results: Here we present the Women4Health (W4H) cohort, a unique cohort comprising up to 300 healthy women followed up during a natural menstrual cycle, set up with the primary goal to investigate the combined role of sex hormones and gut microbiota variations in regulating host lipid and glucose metabolism during homoeostasis, using a multi-omics strategy. Additionally, the W4H cohort will take into consideration another ecosystem that is unique to women, the vaginal microbiome, investigating its interaction with gut microbiome and exploring-for the first time-its role in cardiometabolic disorders. Conclusion: The W4H cohort study lays a foundation for improving current knowledge of women-specific mechanisms in cardiometabolic regulation. It aspires to transform insights on host-microbiota interactions into prevention and therapeutic approaches for personalized health care.

Puzzling Out the Genetic Architecture of Endometriosis: Whole-Exome Sequencing and Novel Candidate Gene Identification in a Deeply Clinically Characterised Cohort.

Endometriosis (EM) is a common multifactorial gynaecological disorder. Although Genome-Wide Association Studies have largely been employed, the current knowledge of the genetic mechanisms underlying EM is far from complete, and other approaches are needed. To this purpose, whole-exome sequencing (WES) was performed on a deeply characterised cohort of 80 EM patients aimed at the identification of rare and damaging variants within 46 EM-associated genes and novel candidates. WES analysis detected 63 rare, predicted, and damaging heterozygous variants within 24 genes in 63% of the EM patients. In particular, (1) a total of 43% of patients carried variants within 13 recurrent genes (FCRL3, LAMA5, SYNE1, SYNE2, GREB1, MAP3K4, C3, MMP3, MMP9, TYK2, VEGFA, VEZT, RHOJ); (2) a total of 8.8% carried private variants within eight genes (KAZN, IL18, WT1, CYP19A1, IL1A, IL2RB, LILRB2, ZNF366); (3) a total of 24% carried variants within three novel candidates (ABCA13, NEB, CSMD1). Finally, to deepen the polygenic architecture of EM, a comprehensive evaluation of the analysed genes was performed, revealing a higher burden (p < 0.05) of genes harbouring rare and damaging variants in the EM patients than in the controls. These results highlight new insights into EM genetics, allowing for the definition of novel genotype-phenotype correlations, thereby contributing, in a long-term perspective, to the development of personalised care for EM patients.

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma.

Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.

A Targeted Proteomics Approach for Screening Serum Biomarkers Observed in the Early Stage of Type I Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic malignancy, and it arises in the inner part of the uterus. Identification of serum biomarkers is essential for diagnosing the disease at an early stage. In this study, we selected 44 healthy controls and 44 type I EC at tumor stage 1, and we used the Immuno-oncology panel and the Target 96 Oncology III panel to simultaneously detect the levels of 92 cancer-related proteins in serum, using a proximity extension assay. By applying this methodology, we identified 20 proteins, associated with the outcome at binary logistic regression, with a p-value below 0.01 for the first panel and 24 proteins with a p-value below 0.02 for the second one. The final multivariate logistic regression model, combining proteins from the two panels, generated a model with a sensitivity of 97.67% and a specificity of 83.72%. These results support the use of the proposed algorithm after a validation phase.

A Systematic Review of the Guidelines on Venous Thromboembolism Prophylaxis in Gynecologic Oncology.

(1) Background: This review aimed to summarize the indications for venous thromboembolic (VTE) events' prophylaxis in a gynecological cancer population, according to the most recent guidelines. (2) Methods: A systematic review of the guidelines in PubMed, SCOPUS, Web of Science, EMBASE, and CINHAL regarding VTE prevention in gynecological cancer patients was conducted according to PRISMA criteria. We compared the recommendations given by oncological and hematological societies regarding VTE prevention in gynecological cancer patients published from January 2010 through March 2021. We searched for the following keywords: "venous thromboembolism prevention", "cancer", and "guidelines". The AGREE II checklist was used to critically analyze the guidelines' quality. (3) Results: There were 1003 documents available; 14 met the inclusion criteria, 5 were excluded and, eventually, the guidelines of 10 societies were evaluated. (4) Conclusions: The guidelines agree that low-molecular-weight heparin (LMWH) and fondaparinux achieve better results in VTE prevention in gynecological cancer patients. Direct oral anticoagulants (DOACs) can be used to prevent VTE in outpatients and high-risk medical patients after discharge. VTE risk scores should be applied to all oncological patients to identify those who would benefit from a prevention program. More attention should be paid to mechanical prophylactic methods due to the high bleeding risk of gynecological cancer patients.

Ultrasound Imaging of Acquired Myometrial Pseudoaneurysm: The Role of Manipulators as an Unusual Cause during Laparoscopic Surgery.

An acquired uterine artery myometrial pseudoaneurysm can occur due to inflammation, trauma, or iatrogenic causes, such as surgical procedures, and can lead to profuse bleeding. The efficacy of uterine manipulators in gynecological surgery, particularly as a cause of a pseudoaneurysm, has been poorly discussed in the literature. In this paper, we discuss a case of a 39-year-old woman with profuse uterine bleeding that occurred seven days after operative laparoscopic surgery for endometriosis. The color Doppler ultrasound better evoked the arterial-like turbulent blood flow inside this cavity. These sonographic features were highly suggestive of uterine artery pseudoaneurysm, presumably related to a secondary trauma caused by the manipulator. The diagnosis was subsequently re-confirmed by angiography, and the patient was treated conservatively with uterine artery embolization. Ultrasound has been shown to be a valuable and safe tool for imaging pseudoaneurysm and guiding subsequent interventional procedures. Accordingly, we briefly review the most suitable manipulators used in benign gynecological surgeries to verify if the different types in use can guide the surgeon towards the correct choice according to surgical needs and thus prevent potentially dangerous trauma.

A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum.

Endometrial cancers (ECs) are mostly adenocarcinomas arising from the inner part of the uterus. The identification of serum biomarkers, either soluble or carried in the exosome, may be useful in making an early diagnosis. We used label-free quantification mass spectrometry (LFQ-MS)-based proteomics to investigate the proteome of exosomes in the albumin-depleted serum from 12 patients with EC, as compared to 12 healthy controls. After quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 33 proteins in EC vs. control samples, with a fold change of ≥1.5 or ≤0.6. Validation using Western blotting analysis in 36 patients with EC as compared to 36 healthy individuals confirmed the upregulation of APOA1, HBB, CA1, HBD, LPA, SAA4, PF4V1, and APOE. A multivariate logistic regression model based on the abundance of these proteins was able to separate the controls from the EC patients with excellent sensitivity levels, particularly for stage 1 ECs. The results show that using LFQ-MS to explore the specific proteome of serum exosomes allows for the identification of biomarkers in EC. These observations suggest that PF4V1, CA1, HBD, and APOE represent biomarkers that are able to reach the clinical stage, after a validation phase.

Advanced photodynamic therapy with an engineered M13 phage targeting EGFR: Mitochondrial localization and autophagy induction in ovarian cancer cell lines.

Photodynamic therapy (PDT) is a potential synergistic approach to chemotherapy for treating ovarian cancer, the most lethal gynecologic malignancy. Here we used M13 bacteriophage as a targeted vector for the efficient photodynamic killing of SKOV3 and COV362 cells. The M13 phage was refactored (M13r) to display an EGFR binding peptide in its tip that is frequently overexpressed in ovarian cancer. The refactored phage was conjugated with chlorin e6 (Ce6), one of the most widely used photosensitizers (M13r-Ce6). The new platform, upon irradiation, generated ROS by type I mechanism and showed activity in killing SKOV3 and COV362 cells even at concentrations in which Ce6 alone was ineffective. A microscopy analysis demonstrated an enhanced cellular uptake of M13r-Ce6 compared to free Ce6 and its mitochondrial localization. Western blot analysis revealed significant downregulation in the expression of EGFR in cells exposed to M13r-Ce6 after PDT. Following PDT treatment, autophagy induction was supported by an increased expression of LC3II, along with a raised autophagic fluorescent signal, as observed by fluorescence microscopy analysis for autophagosome visualization. As a conclusion we have herein proposed a bacteriophage-based receptor targeted photodynamic therapy for EGFR-positive ovarian cancer.

Anti-inflammatory properties of a proprietary bromelain extract (Bromeyal™) after in vitro simulated gastrointestinal digestion.

INTRODUCTION: Bromelain is a complex mixture of thiol proteases and other non-proteolytic constituents, commercially extracted primarily from the pineapple stem. Evidence from several in vitro and in vivo studies highlights its excellent bioavailability, lack of side effects, and broad spectrum of medical efficacies, of which the antiphlogistic properties are among the most valuable ones. Bromelain has indeed been employed for the efficient treatment of many inflammatory disorders, ranging from osteoarthritis and inflammatory bowel diseases to cancer-related inflammation. METHODS: The aim of the current study was to assess the anti-inflammatory effects of bromelain after gastrointestinal digestion simulated in vitro using stomach, intestinal, and chondrocyte human cellular models (AGS, Caco-2, and SW1353, respectively). RESULTS: We successfully demonstrated the capability of bromelain to reduce an inflammatory stimulus by reproducing its exposure to the gastro-enteric environment in vitro and assaying its effect in human cell lines derived from stomach, intestinal, and chondrocytes. CONCLUSION: Consistently with the previously published data, our work underpins the relevance of bromelain in the development of safer and more effective anti-inflammatory therapies.

Efficacy and safety of a new vaginal gel for the treatment of symptoms associated with vulvovaginal atrophy in postmenopausal women: A double-blind randomized placebo-controlled study.

OBJECTIVE: The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18ß-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks. STUDY DESIGN: Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 1:1 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days. MAIN OUTCOME MEASURE: The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function. RESULTS: Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P < .0001), and in reducing each VVA symptom (vaginal dryness, vaginal itching, burning sensation) at weeks 2 and 4, and the end of the study (P < .0001). The analysis of FSFI scores showed, after the end of treatment, an improvement of sexual function in the active-treatment group, with a statistically significant increase (P < 0.001) in all domains scores and total score (P < 0.001). CONCLUSIONS: The present single-center randomized clinical trial demonstrated the efficacy, tolerability and safety of 12-week treatment with a new vaginal gel in postmenopausal women with symptoms associated with VVA. Based on this trial, the gel seems to be a valid choice as a single, local agent for relieving VVA symptoms and improving sexual function, and to have good compliance. This trial is registered prospectively with the Clinical Trials Registry - India, number CTRI/2019/05/01911.