Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: A systematic review and meta-regression.

BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.

Time to bring female genital schistosomiasis out of neglect.

BACKGROUND: Female genital schistosomiasis (FGS) is a chronic gynaecological disease affecting girls and women in sub-Saharan Africa (SSA), caused by the parasite Schistosoma (S.) haematobium. FGS is associated with sexual dysfunction, reproductive tract morbidity and increased prevalence of HIV and cervical precancer lesions. SOURCE OF DATA: Key peer-reviewed published literature. AREAS OF AGREEMENT: FGS screening and diagnosis require costly equipment and specialized training, seldom available in resource-limited settings. FGS surveillance is not included in wider schistosomiasis control strategies. The interplay of FGS with other SRH infections is not fully understood. Integration of FGS within sexual and reproductive health (SRH) control programmes needs to be explored. AREAS OF CONTROVERSY: There are no standardized methods for individual or population-based FGS screening and diagnosis, hindering accurate disease burden estimates and targeted resource allocation. Treatment recommendations rely on public health guidelines, without rigorous clinical evidence on efficacy. GROWING POINTS: Integrating FGS screening with SRH programmes offers an opportunity to reach at-risk women with limited access to healthcare services. Home-based self-sampling coupled with handheld colposcopes operated by primary healthcare workers show promise for FGS diagnosis and surveillance at scale. AREAS TIMELY FOR DEVELOPING RESEARCH: There is growing interest in decentralizing strategies for FGS screening and diagnosis. The accurate predictions on the 'cost-effectiveness' of these approaches will determine their affordability and feasibility within the overburdened health systems in SSA. Clinical trials are needed to optimize FGS treatment. Longitudinal studies can expand on the epidemiological knowledge on co-morbidities and integration within other SRH interventions.

Beyond the reproductive tract: gut microbiome and its influence on gynecological health.

PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.

Deciphering the potential of proteomic-based biomarkers in women's reproductive diseases: empowering precision medicine in gynecology.

CONTEXT: Gynecological disorders represent a complex set of malignancies that result from a diverse array of molecular changes affecting the lives of over a million women worldwide. Ovarian, Endometrial, and Cervical cancers, Endometriosis, PCOS are the most prevalent ones that pose a grave threat to women's health. Proteomics has emerged as an invaluable tool for developing novel biomarkers, screening methods, and targeted therapeutic agents for gynecological disorders. Some of these biomarkers have been approved by the FDA, but regrettably, they have a constrained diagnostic accuracy in early-stage diagnosis as all of these biomarkers lack sensitivity and specificity. Lately, high-throughput proteomics technologies have made significant strides, allowing for identification of potential biomarkers with improved sensitivity and specificity. However, limited successes have been shown with translation of these discoveries into clinical practice. OBJECTIVE: This review aims to provide a comprehensive overview of the current and potential protein biomarkers for gynecological cancers, endometriosis and PCOS, discusses recent advances and challenges, and highlights future directions for the field. CONCLUSION: We propose that proteomics holds great promise as a powerful tool to revolutionize the fight against female reproductive diseases and can ultimately improve personalized patient outcomes in women's biomedicine.

Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

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).

Genital chronic graft-versus-host disease: an unmet need that requires trained gynecologists.

OBJECTIVE: Menopause and chronic graft-versus-host disease (cGvHD) are the leading causes of morbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT). Genitalia are one of the target organs of cGvHD causing sexual dysfunction and local symptoms, which may impair women's quality of life. The aim of this study is to describe the prevalence and clinical characteristics of genital cGvHD. METHODS: A retrospective cross-sectional observational study was performed including 85 women with alloHSCT. All women were diagnosed and counseled by a trained gynecologist. Health-related quality of life was assessed by the Cervantes Short-Form Scale and sexual function was evaluated by the Female Sexual Function Index. RESULTS: Seventeen women (20%) included in the study were diagnosed with genital cGvHD. The main complaints were vulvovaginal dryness (42.2%) and dyspareunia (29.4%), the presence of erythema/erythematous plaques (52.9%) being the most frequent sign. Median time from transplant to diagnosis of genital cGvHD was 17 months among those with mild involvement, 25 months for moderate and 42 months for severe forms. Mortality was 29.4% in patients who developed cGvHD with genital involvement versus 8.8% among those without (p = 0.012). CONCLUSION: Early gynecological evaluation might allow to identify patients with mild forms of genital cGvHD, potentially enabling better management and improved outcomes.

Integrated Care for Persons With Persistent Gynecologic Conditions.

Persons with persistent gynecologic conditions frequently cope with complex biopsychosocial challenges and benefit from integrated behavioral health evaluation and treatment within gynecologic practices. Integrated care refers to the provision of behavioral health services within a health care setting which contributes to improved patient, provider, and practice outcomes, however, has not been commonly provided in traditional gynecologic practices. Several models of integrated behavioral health are reviewed. Each model holds specific applications in primary and specialty gynecology settings and may enhance the gynecologic patient experience. This article reviews current research supporting integrated care and describes implementation, funding, and evaluation to improve patient outcomes.

Sexual Dysfunction and Dyspareunia in the Setting of the Genitourinary Syndrome of Menopause.

Sexual dysfunction is a common consequence of the genitourinary syndrome of menopause (GSM). In this book chapter, we discuss the pathophysiology, prevalence, evaluation, and evidence-based management of sexual dysfunction in patients affected by GSM. Additionally, we present an algorithm to guide clinicians in the management and treatment of sexual dysfunction in this setting based on available evidence and best practices.

Validation of the Canadian Institute for Health Information Diagnostic Codes for Benign Gynaecologic Surgery.

We investigated the validity of the 10th Revision Canadian modification of International Statistical Classification of Disease and Related Health Problems (ICD-10-CA) diagnostic codes for surgery for benign gynaecologic conditions in the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD), the main source of routinely collected data in Canada. Reabstracted data from patient charts was compared to ICD-10-CA codes and measures of validity were calculated with 95% confidence intervals. A total of 1068 procedures were identified. More objective, structural diagnoses (fibroids, prolapse) had higher sensitivity and near-perfect Kappa coefficients, while more subjective, symptomatic diagnoses (abnormal uterine bleeding, pelvic pain) had lower sensitivity and moderate-substantial Kappa coefficients. Specificity, positive predictive values, and negative predictive values were generally high for all diagnoses. These findings support the use of CIHI-DAD data for gynaecologic research.

Identifying opportunities for prevention of adverse outcomes following female genital fistula repair: protocol for a mixed-methods study in Uganda.

BACKGROUND: Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify these adverse risks and inform clinical and counseling interventions to optimize women's health and quality of life following fistula repair through: identifying predictors and characteristics of post-repair fistula breakdown and recurrence (Objective 1) and post-repair incontinence (Objective 2), and to identify feasible and acceptable intervention strategies (Objective 3). METHODS: This mixed-methods study incorporates a prospective cohort of women with successful vesicovaginal fistula repair at approximately 12 fistula repair centers in Uganda (Objectives 1-2) followed by qualitative inquiry among key stakeholders (Objective 3). Cohort participants will have a baseline visit at the time of surgery followed by data collection at 2 weeks, 6 weeks, 3 months and quarterly thereafter for 3 years. Primary predictors to be evaluated include patient-related factors, fistula-related factors, fistula repair-related factors, and post-repair behaviors and exposures, collected via structured questionnaire at all data collection points. Clinical exams will be conducted at baseline, 2 weeks post-surgery, and for outcome confirmation at symptom development. Primary outcomes are fistula repair breakdown or fistula recurrence and post-repair incontinence. In-depth interviews will be conducted with cohort participants (n ~ 40) and other key stakeholders (~ 40 including family, peers, community members and clinical/social service providers) to inform feasibility and acceptability of recommendations. DISCUSSION: Participant recruitment is underway. This study is expected to identify key predictors that can directly improve fistula repair and post-repair programs and women's outcomes, optimizing health and quality of life. Furthermore, our study will create a comprehensive longitudinal dataset capable of supporting broad inquiry into post-fistula repair health. Trial Registration ClinicalTrials.gov Identifier: NCT05437939.

Female genital fistula is a traumatic birth injury which occurs where access to emergency childbirth care is poor. It causes uncontrollable urine leakage and is associated with other physical and psychological symptoms. Due to the urine leakage and its odor, women with fistula are stigmatized which has mental health and economic consequences. Ensuring women's access to fistula surgery and ongoing wellbeing is important for limiting the impact of fistula. After fistula surgery, health risks such as fistula repair breakdown or recurrence or changes to urine leakage can happen, but studies during this time are limited. Our study seeks to measure these health risks and factors influencing these risks quantitatively, and work with patients, community members, and fistula care providers to come up with solutions. We will recruit up to 1000 participants into our study at the time of fistula surgery and follow them for three years. We will collect data on patient sociodemographic characteristics, clinical history, and behavior after fistula repair through patient survey and medical record review. If participants have changes in urine leakage, they will be asked to return to the fistula repair hospital for exam. We will interview about 80 individuals to obtain their ideas for feasible and acceptable intervention options. We expect that this study will help to understand risk factors for poor health following fistula repair and, eventually, improve women's health and quality of life after fistula.

Adult genital psoriasis: An updated review for clinicians.

Genital psoriasis is a chronic inflammatory skin condition that has been reported in up to 63% of patients with psoriasis on other parts of their skin. It has a profound impact on quality of life and sexual function which is often overlooked by current severity scores. Despite its prevalence and disease burden, genital psoriasis remains largely under-reported and under-treated. Historically, this was due to the impracticality and limited efficacy data of standard psoriasis treatments when applied to genital skin. However, there have been recent advancements with several new agents currently being developed and evaluated for genital psoriasis. This clinical review aims to provide an overview of the current evidence regarding the clinical features of genital psoriasis, available management options and tools for assessing patients' quality of life. Key takeaways from this review emphasise the recognition of genital psoriasis as a chronic and debilitating condition, unique in its impact on patients' quality of life, necessitating sensitive and attentive approaches to address their needs.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Capturing anatomy in computed tomography scans for genital pathology.

PURPOSE: In this cross-sectional study, we aimed to characterize how frequently the anatomy of interest (AOI) was excluded when evaluating genital pathology using the current CT pelvis protocol recommended by the American College of Radiology and evaluate how AOI exclusion affects patient management. METHODS: We retrospectively reviewed medical records, using diagnosis and CPT codes, of patients admitted with genital pathology who obtained a CT scan at our institution from July 1, 2020-April 30, 2023. Baseline patient demographics were included. Data about each index CT scan (scan obtained at our institution) were recorded and assessed for exclusion of the AOI. Statistical analysis was performed to determine the rate of AOI exclusion and to compare patient management between patients with AOI excluded versus those without AOI exclusion. RESULTS: 113 presentations for genital pathology included an index CT scan and were included for analysis. Patients were primarily men (98%) with a mean age of 53.1 years (SD 13.9). The most common diagnoses were Fournier's gangrene (35%), scrotal abscess (22%) and unspecified infection (19%). 26/113 scans (23%) did not capture the entire AOI. When the AOI was missed during the index scan, there was a higher rate of obtaining additional scans (38% vs. 21%), but a similar rate of intervention (77% vs. 63%) when compared to index scans that captured the entire AOI. 35 scans (31%) had protocol-extending instructions; index scans that captured the entire AOI were more likely to have specific protocol-extending instructions (38% vs. 8% p < 0.01). CONCLUSIONS: Creating a specific CT protocol for genital pathology could decrease the amount of inappropriate irradiation and improve AOI capture rates without relying on specific request for protocol deviation.

The Role of Nanomedicine in Benign Gynecologic Disorders.

Nanomedicine has revolutionized drug delivery in the last two decades. Nanoparticles appear to be a promising drug delivery platform in the treatment of various gynecological disorders including uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause. Nanoparticles are tiny (mean size < 1000 nm), biodegradable, biocompatible, non-toxic, safe, and relatively inexpensive materials commonly used in imaging and the drug delivery of various therapeutics, such as chemotherapeutics, small molecule inhibitors, immune mediators, protein peptides and non-coding RNA. We performed a literature review of published studies to examine the role of nanoparticles in treating uterine leiomyoma, endometriosis, PCOS, and menopause. In uterine leiomyoma, nanoparticles containing 2-methoxyestradiole and simvastatin, promising uterine fibroid treatments, have been effective in significantly inhibiting tumor growth compared to controls in in vivo mouse models with patient-derived leiomyoma xenografts. Nanoparticles have also shown efficacy in delivering magnetic hyperthermia to ablate endometriotic tissue. Moreover, nanoparticles can be used to deliver hormones and have shown efficacy as a mechanism for transdermal hormone replacement therapy in individuals with menopause. In this review, we aim to summarize research findings and report the efficacy of nanoparticles and nanotherapeutics in the treatment of various benign gynecologic conditions.

Extragenital lichen sclerosus et atrophicus-morphea overlap as an initial presentation of genital lichen sclerosus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disorder, most often characterized by atrophic skin plaques located on female genitalia. Infrequently, LSA may present extragenitally; however, much is unknown about the temporal relationship between genital and extragenital LSA. Morphea, also known as localized scleroderma, is a rare inflammatory skin condition characterized by sclerotic plaques. Investigators debate whether LSA and morphea exist on the same spectrum of disease, with LSA representing a superficial variant of morphea involving genitalia, or if they are distinct but coincidental entities. Although researchers have described LSA and morphea occurring in different locations on the same patient, few reports describe LSA and morphea occurring in the same lesion and in the inguinal folds. Herein, we report a case of a 62-year-old woman with extragenital LSA-morphea overlap in the inguinal folds, who three months later developed genital LSA. Extragenital LSA-morphea in the same plaque, with no signs of genital lesions on initial exam, with later development of genital LSA, is especially uncommon. The temporal progression of extragenital LSA-morphea overlap to genital LSA over a three-month period is an important contribution to the literature, as the temporal relationship between extragenital and genital LSA is not previously discussed.

Copper in Gynecological Diseases.

Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes' and Wilson's diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

Copper homeostasis and cuproptosis in gynecological disorders: Pathogenic insights and therapeutic implications.

This review comprehensively explores the complex role of copper homeostasis in female reproductive system diseases. As an essential trace element, copper plays a crucial role in various biological functions. Its dysregulation is increasingly recognized as a pivotal factor in the pathogenesis of gynecological disorders. We investigate how copper impacts these diseases, focusing on aspects like oxidative stress, inflammatory responses, immune function, estrogen levels, and angiogenesis. The review highlights significant changes in copper levels in diseases such as cervical, ovarian, endometrial cancer, and endometriosis, underscoring their potential roles in disease mechanisms and therapeutic exploration. The recent discovery of 'cuproptosis,' a novel cell death mechanism induced by copper ions, offers a fresh molecular perspective in understanding these diseases. The review also examines genes associated with cuproptosis, particularly those related to drug resistance, suggesting new strategies to enhance traditional therapy effectiveness. Additionally, we critically evaluate current therapeutic approaches targeting copper homeostasis, including copper ionophores, chelators, and nanoparticles, emphasizing their emerging potential in gynecological disease treatment. This article aims to provide a comprehensive overview of copper's role in female reproductive health, setting the stage for future research to elucidate its mechanisms and develop targeted therapeutic strategies.