Menopause-Biology, consequences, supportive care, and therapeutic options.

Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice.

Role of lateral suspension for the treatment of pelvic organ prolapse: a Delphi survey of expert panel.

INTRODUCTION AND HYPOTHESIS: Lateral suspension is an abdominal prosthetic surgical procedure used to correct apical prolapse. The procedure involves the placement of a T-shaped mesh on the anterior vaginal wall and on the isthmus or uterine cervix that is suspended laterally and posteriorly to the abdominal wall. Since its description in the late 90s, modifications of the technique have been described. So far, no consensus on the correct indications, safety, advantages, and disadvantages of this emerging procedure has been reached. METHODS: A modified Delphi process was used to build consensus within a group of 21 international surgeons who are experts in the performance of laparoscopic lateral suspension (LLS). The process was held with a first online round, where the experts expressed their level of agreement on 64 statements on indications, technical features, and other aspects of LLS. A subsequent re-discussion of statements where a threshold of agreement was not reached was held in presence. RESULTS: The Delphi process allowed the identification of several aspects of LLS that represented areas of agreement by the experts. The experts agreed that LLS is a safe and effective technique to correct apical and anterior prolapse. The experts highlighted several key technical aspects of the procedure, including clinical indications and surgical steps. CONCLUSIONS: This Delphi consensus provides valuable guidance and criteria for the use of LLS in the treatment of pelvic organ prolapse, based on expert opinion by large volume surgeons' experts in the performance of this innovative procedure.

Management of obesity in menopause.

The increasing prevalence of obesity imposes significant health challenges, particularly in women undergoing menopause. Effective obesity management is essential to mitigate associated comorbidities and improve quality of life. The pillars of obesity treatment encompass lifestyle modifications, pharmacotherapy and surgical interventions. Pharmacotherapy may be considered for women who do not achieve adequate weight loss through lifestyle changes alone and have obesity or overweight with risk factors. Bariatric surgery is reserved for individuals with severe obesity or those with obesity-related complications. During menopause, hormonal changes contribute to weight gain and fat redistribution, complicating obesity management. Tailored treatment strategies are necessary to address the unique challenges faced by this population. The role of physicians and gynecologists is pivotal in the multidisciplinary approach to obesity management during menopause. Gynecologists are often the primary health-care providers for menopausal women and are in a unique position to offer guidance on weight management. They can provide personalized counseling, coordinate with nutritionists, endocrinologists and bariatric specialists, and monitor the effects of obesity and its treatment on reproductive health. By integrating obesity management into routine gynecological care, gynecologists can significantly impact the overall health and well-being of menopausal women.

Unmet needs in abnormal uterine bleeding due to ovulatory dysfunction.

Ovulatory disorders are a common cause of abnormal uterine bleeding in women of reproductive age. The International Federation of Gynecology and Obstetrics currently offers a causal classification system for ovulatory disorders but does not provide clear management recommendations. There remains regional disparity in treatment practices, often influenced by institutional and insurance regulations as well as cultural and religious practices. A panel of experts evaluated current gaps in ovulatory disorder management guidelines and discussed potential strategies for addressing these unmet needs. Key gaps included a lack in consensus about the effectiveness of combined estrogen and progestogen versus progestogen alone, a paucity of evidence regarding the relative effectiveness of distinct hormonal molecules, a lack of data regarding optimal treatment duration, and limited guidance on optimal sequencing of treatment. Recommendations included development of a sequential treatment-line approach and development of a clinical guide addressing treatment scenarios common to all countries, which can then be adapted to local practices. It was also agreed that current guidelines do not address the unique clinical challenges of certain patient groups. The panel discussed how the complexity and variety of patient groups made the development of one single disease management algorithm unlikely; however, a simplified, decision-point hierarchy could potentially help direct therapeutic choices. Overall, the panel highlighted that greater advocacy for a tailored approach to the treatment of ovulatory disorders, including wider consideration of non-estrogen therapies, could help to improve care for people living with abnormal uterine bleeding due to ovarian dysfunction.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

Robot-assisted pelvic floor reconstructive surgery: an international Delphi study of expert users.

BACKGROUND: Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion. METHODS: We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons' characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis. RESULTS: The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy. CONCLUSION: Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit.

Five actions for five people: emergency cesarean section protocol.

OBJECTIVE: The scope of this work is to evaluate an operative protocol for emergency C-section to improve teamwork and reduce surgical setup time. METHODS: Sixty-six health care operators working together in the delivery ward (gynecologists, midwives, anesthesiologists) simulated an emergency scenario applying a "five actions for each operator" protocol. For each simulation, the decision to delivery interval was considered and the perception of each operator as a team worker was analyzed with specific tests. RESULTS: The "five actions for five people" protocol significantly reduces the decision to delivery interval (p < 0.001) for emergency C-section. At the same time, a simple and codified scheme improves communication among team members, avoids overlapping roles. Indeed, all the operators become more aware of being helpful to the team (p < 0.001). CONCLUSION: The use of a standardized, simple, and immediately usable protocol improves the performance of the delivery room team in terms of the urgency and quality of the operator's participation in the event. Procedures of this type should be favored within emergency obstetric settings. TRIAL REGISTRATION NUMBER: CEAVNO 19-01-23. Local ethical Committee (COMITATO ETICO REGIONALE PER LA SPERIMENTAZIONE CLINICA - Sezione autonoma Area Vasta Nord Ovest -CEAVNO) approved this study as simulation training study. All the operators participated voluntary during their working time.

Hormonal and natural contraceptives: a review on efficacy and risks of different methods for an informed choice.

The debate about contraception has become increasingly important as more and more people seek safe and effective contraception. More than 1 billion women of reproductive age worldwide need a method of family planning, and wellbeing, socio-economic status, culture, religion and more influence the reasons why a woman may ask for contraception. Different contraceptive methods exist, ranging from 'natural methods' (fertility awareness-based methods - FABMs) to barrier methods and hormonal contraceptives (HCs). Each method works on a different principle, with different effectiveness.FABMs and HCs are usually pitted against each other, although it's difficult to really compare them. FABMs are a valid alternative for women who cannot or do not want to use hormone therapy, although they may have a high failure rate if not used appropriately and require specific training. HCs are commonly used to address various clinical situations, although concerns about their possible side effects are still widespread. However, many data show that the appropriate use of HC has a low rate of adverse events, mainly related to personal predisposition.The aim of this review is to summarize the information on the efficacy and safety of FABMs and HCs to help clinicians and women choose the best contraceptive method for their needs.

Mutation of aspartic acid 262 on estrogen receptor abrogates estradiol signaling pathway.

OBJECTIVE: ERα (estrogen receptor alpha) exerts nuclear genomic actions and membrane-initiated non-genomic effects. The mutation of aspartic acid into alanine in vitro revealed the critical role of aspartic acid 258 (corresponding to mouse amino acid site 262) of ERα for non-nuclear function. Our previous in vitro study revealed that this mutation blocked estrogen's non-genomic effects on vascular endothelial H2S release. Here, we studied the in vivo role of the aspartic acid 262 of ERα in the reproductive system and in the vascular tissue. APPROACH AND RESULTS: We generated a mouse model harboring a point mutation of the murine counterpart of this aspartic acid into alanine (ERαD262A). Our results showed that the ERαD262A females are fertile with standard hormonal serum levels, but the uterine development and responded with estrogen and follicular development are disrupted. In line with our previous study, we found that the rapid dilation of the aorta was abrogated in ERαD262A mice. In contrast to the previously reported R264-ERα mice, the classical estrogen genomic effector SP1/NOS3/AP1 and the nongenomic effectors p-eNOs, p-AKT, and p-ERK were disturbed in the ERαD262A aorta. Besides, the serum H2S concentration was decreased in ERαD262A mice. Together, ERαD262A mice showed compromised both genomic and non-genomic actions in response to E2. CONCLUSIONS: These data showed that aspartic acid 262 of ERα are important for both genomic and non-genomic effects of E2. Our data provide a theoretical basis for further selecting an effective non-genomic mouse model and provide a new direction for developing estrogen non-genomic effect inhibitors.

An adrenal cortical adenoma with neuroendocrine-type granules mimicking pheochromocytoma.

Clinical and biochemical presentation of adrenal tumors may rarely conflict with their histologic features. In the present report, we describe a rare case of adrenal neoplasm clinically and biochemically labeled as pheochromocytoma which at histologic examination resulted adrenal cortical tumor. The neoplasm was examined with the electron microscope which revealed the presence of electron-dense neuroendocrine-type granules next to intracytoplasmic lipid droplets. The patient underwent laparoscopic left adrenalectomy which leads to normalization of 24 h urinary metanephrine and normetanephrine. This exceptional entity should be taken into consideration when the clinical and laboratory features conflict with the histological examination. The pathologist can clarify the mixed nature of the tumor by means of the identification of neuroendocrine granules at the electron microscope examination.

Technical features, perioperative and anatomical outcomes of a standardized suturing pattern for robotic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Several technical alternatives to repair mesh using laparoscopic sacrocolpopexy exist. We aim to describe the outcomes and surgical technique of robotic-assisted colpo-/cervicosacropexy using a standardized suturing scheme to repair the mesh. METHODS: We retrospectively reported data of 60 consecutive cases of robotic-assisted colpo-/cervicosacropexy for advanced multicompartmental prolapse using a standardized suturing design. We placed three non-absorbable stitches on the cervix or three absorbable stitches on the apex of the vaginal vault, six long-term absorbable stitches on the anterior vaginal wall deep to the basis of the vesical trigone, six similar posterior stitches with the deeper row of sutures down to the levator ani plane and three non-absorbable stitches on the sacral promontory as the cranial support for Y-shaped polypropylene mesh. RESULTS: Median operative time was 188 ± 43 min. All the procedures were successfully performed using a Da Vinci Si platform in a three-arm configuration, and no conversion to open or traditional laparoscopic surgery was needed. The length of hospital stay was 1.2 ± 1.7 days, and no readmission within 30 postoperative days was reported. At a follow-up of 12 and 24 months, no case of extrusion or exposure of the mesh occurred, and the retreatment rate was 6.7%. CONCLUSIONS: Our suturing technique is safe and effective, with negligible risk of complications and good medium-term results. It is plausible that robotic systems may facilitate precise, accurate and reproducible placement of the stitches, thereby favoring wider diffusion of minimally invasive treatment of advanced prolapse.

17ß-Estradiol nongenomically induces vasodilation is enhanced by promoting phosphorylation of endophilin A2.

ObjectiveA previous study found that the tyrosine phosphorylation of endophilin A2 (Endo II) was responsible for increase surface expression of MT1-MMP and ECM degradation; however, there is little information about whether Endo II could influence membrane estrogen receptors (mERs) and its functions.Materials and methodsIn the present study, Human umbilical vein endothelial cells (HUVECs) were treated with E2, PPT, DPN, ICI 182780, Endo siRNA or negative control siRNA, and the biological behavior of the treated cells was observed. The mice were randomly divided into AAV-control-shRNA + Ach, AAV-Endo II-shRNA + Ach, AAV-control-shRNA + E2, AAV-Endo II-shRNA + E2 groups and the thoracic aorta were isolated, cut into 2-mm rings, then the wall tension was detected.ResultsWe found that 17ß-Estradiol (E2) enhanced mERα protein level, which was further increased after knocking down Endo II, the mechanism maybe involved in E2-induced tyrosine phosphorylation of Endo II. In addition, we also observed that Endo II blocked the activation of Akt, ERK1/2 and eNOS signaling in HUVECs treated with E2. E2 induced vasodilation was significantly increased by silencing of Endo II expression.ConclusionOur study provided a sound basis to selective modulate Endo II for E2's nongenomic pathway, which can be benefit for cardiovascular system.

Impact on ovarian reserve and fertility using carbon dioxide laser for endometriosis treatment: a systematic review.

BackgroundThe application of carbon dioxide (CO2) laser for laparoscopic gynecologic surgery was introduced in 1979 and spread after improving instrumentation, due to the versatility of the CO2 laser technology and the parallel increase of laparoscopic use. In a gynecologic setting, laser laparoscopy has been demonstrated to be effective in treating infertility and pain associated with mild to severe endometriosis.Aim and methods: This document aims at conducting a systematic review to provide a comprehensive literature overview regarding the rationale, indications, safety, and efficacy of CO2 laser treatment of endometriosis and related outcomes on ovarian reserve and fertility.ResultsCO2 laser seems to lead to lower heat damage in the ovarian tissue than bipolar energy during endometriomas treatment. Moreover, several reports have pointed out that laser vaporization allows to selectively destroy the endometrioma wall's internal surface, preserving the pericystic fibrotic capsule or the adjacent healthy ovarian cortex. Despite this, robust data we have so far indicates that the most effective laparoscopic approach for managing endometriomas is the traditional excisional technique providing better postoperative outcomes than drainage and electrocoagulation, and laser treatment. Data about fertility after treatment of deep infiltrating endometriosis (DIE) using dioxide laser are emerging but very poor.ConclusionsCurrent scientific evidence in this field is inconclusive, and the debate about the safety and efficacy of the CO2 laser on fertility outcomes is still ongoing. Further randomized case-control studies are mandatory to attain more consistent evidence.

Familial diabetes predisposes PCOS patients to insulin resistance (IR), reproductive impairment and hepatic dysfunction: effects of d-chiro inositol (DCI) and alpha lipoic acid (ALA) administration on hepatic insulin extraction (HIE) index.

ObjectivePCOS is a syndrome is characterized by 2 out of 3 of the criteria established during the Rotterdam Consensus Conference. Recently the issue of insulin resistance (IR) has caught attention.SubjectsA group of overweight/obese PCOS patients (n = 30) have been evaluated before and after 3 months of daily integrative administration of d-chiro inositol (DCI) (500 mg) and alpha lipoic acid (ALA) (300 mg).MethodsHormonal and metabolic profiles, oral glucose tolerance test (OGTT) for glucose, insulin and C-peptide response were performed in baseline conditions and after DCI plus ALA treatment. Hepatic Insulin Extraction (HIE) index was computed along the OGTT to evaluate the liver ability in degrading insulin.ResultsThe treatment decreased LH, Androstenedione (A), insulin plasma levels, BMI, HOMA index, AST and ALT. Considering patients for the presence (n = 17) or absence of familial diabetes (n = 13), the greatest improvements occurred in the former patients. Insulin response to OGTT was greatly reduced after the treatment interval in PCOS with familial diabetes. HIE computation disclosed that in presence of familial diabetes liver degradation of insulin is reduced thus leaving a higher amount of circulating insulin. DCI plus ALA administration decreased AST and ALT and restored hepatic insulin clearance since HIE profile was improved.ConclusionOur study demonstrates that in overweight/obese PCOS the predisposition to familial diabetes triggers IR not only through the endogenous impaired DCI and ALA synthesis but also through a reduced hepatic clearance of insulin. DCI plus ALA administration positively improved hormonal, metabolic profiles as well as liver function.

Mood disorders and hormonal status across women's life: a narrative review.

Depressive disorders and anxiety states represent one of the most frequent psychiatric pathologies occurring transiently in vulnerable women throughout their life, from puberty to menopause. It is now known that sex hormones play a key role on the nervous system, interfering with neuronal plasticity and enhancing the processes of learning, memory, cognition, and mood. Numerous mechanisms are at the base of these processes, displaying interactions between estrogen and serotoninergic, dopaminergic, and GABAergic receptors at the central level. Therefore, given the sexual steroids fluctuations throughout the entire female lifespan, and considering the role played by sex hormones at the central level, it is not surprising to observe the onset of mood or neurodegenerative disorders over time. This is especially true for women in hormonal transition phase, such as puberty, postpartum and the menopausal transition. Moreover, all these conditions are characterized by hormone withdrawal, imbalance, or modifications due to menopausal hormone therapies or contraceptives which could prompt to a deterioration of mood and cognition impairment or to an improvement in the quality of life. More studies are needed to better understand the hormone-related effects on the nervous system, and the underlying pathways involved in transitional or chronic mood disorders, to promote new patient-specific therapeutic strategies more effective than the current ones and tailored according to the individual need and women's life period.

Spotlight on the role of human papillomavirus vaccines.

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Simulation training program for vacuum application to improve technical skills in vacuum-assisted vaginal delivery.

OBJECTIVE: evaluation of technical skills of the operators during the obstetrical device application for operative vaginal delivery, named kiwi-cup in a simulation training program. METHODS: Thirty-five residents in obstetrics and gynecology of the University of Pisa, Italy were recruited and evaluated with an assessment scale on technical skills from 0 to 55 points. They performed various operative vaginal delivery simulations with kiwi-cup and were evaluated at time 0 by a tutor. After 8 weeks, simulation training was repeated and trainees were re-evaluated by the same tutor. RESULTS: after 8 weeks from the first simulation session, trainees have been shown to increase technical skills (46.27 ± 4.6 with p-value < 0.0001), the successful application rate (85.71% with p-value 0.0161).) and to reduce the time to complete the procedure (86.2 ± 29.9 s with p-value < 0.0001). CONCLUSION: simulation training on operational vaginal delivery significantly increases technical skills, improves successful rate, and reduces the time taken to complete the procedure. CLINICAL TRIAL REGISTRATION: Not applicable.

The role of Gα protein signaling in the membrane estrogen receptor-mediated signaling.

Estrogens exert rapid, extranuclear effects by their action on the plasma membrane estrogen receptors (mERs). Gα protein associated with the cell membrane is involved in many important processes regulated by estrogens. However, the Gα's role in the mER-mediated signaling and the signaling pathways involved are poorly understood. This review aims to outline the Gα's role in the mER-mediated signaling. Immunoblotting, immunofluorescence, co-immunoprecipitation, and RNA interference were carried out using vascular endothelial cells (ECs) and human breast carcinoma cell lines as experimental models. Electrophysiology and immunocytochemistry were carried out using guinea pigs as animal models. Recent advances suggest that the signaling of mERα through Gα is required for vascular EC migration or endothelial H2S release, while Gα13 is involved in estrogen-induced breast cancer cell invasion. Besides, the Gαq-coupled PLC-PKC-PKA pathway is critical for the neural regulation of energy homeostasis. This review summarizes the contributions of Gα to mER-mediated signaling, including cardiovascular protection, breast cancer metastasis, neural regulation of homeostatic functions, and osteogenesis.