Empowering Strategies for Lifestyle Interventions, Diet Modifications, and Environmental Practices for Uterine Fibroid Prevention; Unveiling the LIFE UP Awareness.

Uterine fibroids (UFs) are the most common prevalent benign tumor among women of reproductive age, disproportionately affecting women of color. This paper introduces an innovative management strategy for UFs, emphasizing the curbing of disease prevention and progression. Traditionally, medical intervention is deferred until advanced stages, necessitating invasive surgeries such as hysterectomy or myomectomy, leading to high recurrence rates and increased healthcare costs. The strategy, outlined in this review, emphasizes UF disease management and is named LIFE UP awareness-standing for Lifestyle Interventions, Food Modifications, and Environmental Practices for UF Prevention. These cost-effective, safe, and accessible measures hold the potential to prevent UFs, improve overall reproductive health, reduce the need for invasive procedures, and generate substantial cost savings for both individuals and healthcare systems. This review underscores the importance of a proactive UF management method, paving the way for future research and policy initiatives in this domain.

BRCA 1/2 mutations and risk of uterine cancer: a systematic review and meta-analysis.

PURPOSE: In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence. MATERIAL AND METHOD: We systematically searched three databases including PubMed, Scopus, and Google Scholar up to August 2023; and reviewed 23 cohorts and cross-sectional studies to explore the association between BRCA1/2 mutations and uterine cancer incidence. RESULTS: This systematic review comprised a total of 21 cohort studies and 2 cross-sectional studies after the screening process. According to meta-analysis the prevalence of the BRCA1/2 gene in patients with uterine cancer was 0.02 (95%CI = [0.01,0.03], P < 0.01, I2 = 94.82%) CONCLUSIONS: Our meta-analysis investigates a 2% prevalence of BRCA1/2 mutation in patients with uterine cancer. Patients with BRCA1/2 mutations might be more conscious of uterine malignancies.

Evidence-Based Approach for Secondary Prevention of Uterine Fibroids (The ESCAPE Approach).

Uterine fibroids (UFs) are common tumors in women of reproductive age. It is imperative to comprehend UFs' associated risk factors to facilitate early detection and prevention. Simple relying on surgical/pharmacological treatment of advanced disease is not only highly expensive, but it also deprives patients of good quality of life (QOL). Unfortunately, even if the disease is discovered early, no medical intervention is traditionally initiated until the disease burden becomes high, and only then is surgical intervention performed. Furthermore, after myomectomy, the recurrence rate of UFs is extremely high with the need for additional surgeries and other interventions. This confused approach is invasive and extremely costly with an overall negative impact on women's health. Secondary prevention is the management of early disease to slow down its progression or even halt it completely. The current approach of watchful observation for early disease is considered a major missed opportunity in the literature. The aim of this article is to present an approach named the ESCAPE (Evidence-Based Approach for Secondary Prevention) of UF management. It comprises simple, inexpensive, and safe steps that can arrest the development of UFs, promote overall reproductive health, decrease the number of unnecessary surgeries, and save billions of health care systems' dollars worldwide.

A Systematic Review of Vitamin D and Fibroids: Pathophysiology, Prevention, and Treatment.

Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential therapy for uterine fibroids based on experimental and epidemiologic evidence. The objective of this systematic review was to evaluate the role of vitamin D in the pathophysiology of uterine fibroids and its efficacy for prevention and treatment of fibroids. A comprehensive search was conducted of Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to March 2022. English-language publications that evaluated vitamin D and uterine fibroids in humans, whether experimental or clinical, were considered. The search yielded 960 publications, and 89 publications met inclusion criteria: 23 preclinical studies, 25 clinical studies, and 41 review articles. Preclinical studies indicated that the vitamin D receptor was decreased in fibroid cells. Vitamin D treatment of fibroid cells decreased proliferation, extracellular matrix protein expression, and Wnt/ß-catenin signaling. Fourteen clinical studies (n = 3535 participants) assessed serum vitamin D level in women with ultrasound-proven fibroids, and all found an inverse correlation between serum vitamin D level and presence of fibroids. Five clinical studies (n = 472 patients) evaluated treatment of fibroids with vitamin D. Four of five studies showed vitamin D significantly inhibited fibroid growth. One pilot study (n = 109 patients) of vitamin D for secondary prevention of fibroids demonstrated smaller recurrent fibroids in the treated group. These studies provide evidence for vitamin D as a therapy for uterine fibroids and underscore the need for well-designed, randomized, placebo-controlled clinical trials.

Clinical assessment of prophylactic chemotherapy in treating with hydatidiform mole: A protocol for systematic review and meta-analysis.

BACKGROUND: Hydatidiform mole (HM) is more common as molar pregnancy. It is a disease classified under the category of gestational trophoblastic diseases, which could metastasize after originating in the placenta. A majority of females suffering from molar pregnancies are curable by evacuating retained products of conception and the patient's fertility is preserved. In some cases, the growth perseveres and leads to gestational trophoblastic neoplasia, which is an extremely malicious condition that needs chemo-based treatment. There is a possibility to lessen the risk of gestational trophoblastic disease in females with HM through the administration of prophylactic chemo. Yet, there is controversy regarding prophylactic chemotherapy administered pre-or-post removal of HM to curtail the malignant sequelae. Therefore, we will conduct this research to assess both the efficacy as well as security of using prophylactic chemotherapy to treat HM. METHODS: In the preliminary review, the authors will search for randomized controlled trials involving prophylactic chemotherapy to treat HM. The literature search is carried out in the following electronic databases from their inception to May 2021: Chinese National Knowledge Infrastructure, Chinese BioMedical Literature, and WanFang database are the three Chinese language databases. Web of Science, PubMed, Cochrane Library, and EMBASE are the four English language databases. The authors will also perform a manual search through the bibliographies in related literature to find extra articles and ongoing studies. Two independent authors will assess the literature according to an inclusion criteria, use a specialized data collection table to extract data, and use the Cochrane 'Risk of bias' tool for evaluating any possible bias risk in the selected articles. Data synthesis and statistical operations are completed with the RevMan software (v. 5.3). RESULTS: The present systematic analysis provides a rationalized synthesis of existing evidence related to the use of prophylactic chemotherapy in the treatment of HM. CONCLUSION: Our findings will summarize the current evidences for prophylactic chemotherapy in the treatment of HM. ETHICS AND DISSEMINATION: An ethics approval is nonrequired because pre published results will be used. REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6QV52 (https://osf.io/6qv52/).

The Future of Uterine Fibroid Management: a More Preventive and Personalized Paradigm.

Uterine fibroids are the most common tumors of the female reproductive tract, affecting up to 80% of women. Despite their heavy burden and high prevalence, available medical treatment options are limited and are offered to patients assuming equal responsiveness. These benign tumors are complex, originating from potentially diverse pathobiologic processes, yet they are all managed in a rather standardized symptom-oriented approach that does not take into account the underlying processes. With our increasing understanding of the interplay between genes, epigenetics, individual's lifestyle, and the environment in disease development, uterine fibroid management should be geared towards individualized preventive and treatment options. For example, it seems that some subsets of patients with fibroids also suffer from vitamin D deficiency, hypertension, metabolic syndrome, or other conditions. It is possible that these subsets may have different underlying processes and different responsiveness to different treatment options. Herein, we call for a futuristic paradigm shift of research to develop a new model to manage uterine fibroids with the treatment approach varying depending on the patient's perceived underlying processes as assessed by medical, social, family history, and relevant investigations. This is only possible through the collaboration of scientists, physicians, and funding agencies and with the help of our patients.

Factores de riesgo del cáncer cérvico uterino en adolescentes de la Universidad de Ciencias Médicas de Matanzas / Risk factors of cervical cancer in adolescents of the Matanzas University of Medical Sciences

RESUMEN Introducción: el cáncer cérvico uterino constituye un problema de salud para la humanidad. El estudio de sus factores de riesgo representa prioridad para el sistema de salud cubano. Objetivo: conocer el comportamiento de los factores de riesgo del cáncer cérvico uterino, en estudiantes de las carreras de Higiene-Epidemiología-Vigilancia y Lucha Antivectorial de la Universidad de Ciencias Médicas de Matanzas. Materiales y métodos: investigación descriptiva, transversal, retrospectiva que se insertó en el Programa Ramal Enfermedades Crónicas no Transmisibles. Se trabajó con el universo de 50 alumnos de las carreras de Higiene- Epidemiología-Vigilancia y Lucha Antivectorial de la Universidad de Ciencias Médicas de Matanzas. Resultados: según edad de inicio de las relaciones sexuales, se observó mayor predominio a los 14 años de edad. Presencia de múltiples compañeros sexuales, relaciones sexuales desprotegidas, uso de tabletas anticonceptivas, hábito de fumar, manipulaciones ginecológicas, así como infecciones de transmisión sexual. Especial significación tuvo la evidencia de cifras significativas de múltiples compañeros sexuales y el uso de tabletas anticonceptivas. Entre la distribución de motivos que impulsaron al inicio de relaciones sexuales, se destacaron los de experimentar sensaciones nuevas con el 28 %, y búsqueda de placer con la pareja en 55 %. El 92 %, desconocían los factores de riesgo de la enfermedad. Conclusiones: los estudiantes presentaron factores de riesgo de considerable magnitud de padecer cáncer cérvico uterino (AU).

SUMMARY Introduction: cervical cancer is a health problem for the humankind. The study of its risk factors stands as a priority for the Cuban health system. Objective: to know the behavior of cervical cancer risk factors in students of the studies of Hygiene-Epidemiology-Vector Surveillance and Control of the Matanzas University of Medical Sciences. Materials and methods: retrospective, cross-sectional, descriptive research inserted into the Branch Program of Chronic Non-communicable Diseases. It dealt with the universe of 50 students of the studies of Hygiene-Epidemiology-Vectorial Surveillance and Control of the Matanzas University of Medical Sciences. Results: in relation to the age of beginning to have sexual relationships, it was observed the predominance of the age of 14 years. The presence of multiple sexual partners, unprotected intercourse, use of contraceptive tablets, smoking habit, gynecological manipulations, and sexually transmitted infections are other risk factors found. Special significance had the existence of multiple sexual partners and the use of contraceptive tables. Among the motivations leading to early beginning to have sexual relationships, experiencing new sensations with 28 % and seeking for pleasure with the couple with 55 % stood out. 92 % did not know the disease's risk factors. Conclusions: the students presented pronounced magnitude risk factors of suffering cervical cancer (AU).

Frequency and prediction of deep uterine involvement in advanced high-grade epithelial ovarian cancer: is uterine preservation an option?

INTRODUCTION: Hysterectomy is traditionally part of the surgical treatment for advanced high-grade epithelial ovarian carcinomas, although the incidence of uterine involvement has not been fully investigated. Some young patients with advanced high-grade epithelial ovarian carcinomas want uterine preservation. We aimed to determine the frequency of non-serosal (deep) uterine involvement in patients with high-grade epithelial ovarian carcinomas and to establish predictive factors for such involvement. METHODS: A retrospective cohort study was performed of 366 consecutive patients with advanced high-grade epithelial ovarian carcinomas who had surgery between January 2012 and December 2019. Data collected included demographic and clinical details, and surgical and pathological reports to determine macroscopic and microscopic deep uterine involvement. The characteristics of the patients with and without deep uterine involvement were compared and univariate and multivariate Cox proportional hazard models were used to assess correlations and determine risk factors. RESULTS: A total of 311 patients were included in the final analysis. The mean age was 62±11.6 years, with 32 (10.3%) being younger than 45. Most (92.3%) had serous carcinoma. Uterine involvement, excluding superficial (serosa-only), was present microscopically in 194 patients (62.4%) but was detected macroscopically at surgery in only 166 patients. Deep involvement was missed at surgery in 28 patients (14.4%), including parametrial involvement (n=18), parametria plus cervix (n=2), cervical involvement (n=3), endometrium (n=3), and myometrium (n=2). Multivariate analysis identified factors associated with deep uterine involvement including residual disease at surgery (HR 2.43, 95% CI 1.13 to 4.48; p=0.004) and CA125 >1000 U (HR 1.8, 95% CI 1.09 to 2.94; p=0.02). CONCLUSIONS: The incidence of deep uterine involvement in high-grade epithelial ovarian carcinomas is high. It can be diagnosed in most but not all cases on gross examination at surgery and is associated with residual disease and CA125 >1000 U. Patients who desire uterine preservation should be advised on an individual basis, given these factors and the operative findings.

Vitamins and Uterine Fibroids: Current Data on Pathophysiology and Possible Clinical Relevance.

Uterine fibroid (UF) is the most common benign tumor pathology of the female reproductive organs. UFs constitute the main reason for a hysterectomy and hospitalization due to gynecological conditions. UFs consist of uterine smooth muscle immersed in a large amount of extracellular matrix (ECM). Genetic studies have demonstrated that UFs are monoclonal tumors originating from the myometrial stem cells that have underwent specific molecular changes to tumor initiating stem cells which proliferate and differentiate later under the influence of steroid hormones. There is growing interest in the role of micronutrients, for example, vitamins, in UFs. This article is a comprehensive review of publications regarding the available data concerning the role of vitamins in the biology and management of UFs. In summary, the results showed that some vitamins are important in the biology and pathophysiology of UFs. For example, vitamins A and D deserve particular attention following studies of their influence on the treatment of UF tumors. Vitamins B3, C, and E have not been as widely studied as the abovementioned vitamins. However, more research could reveal their potential role in UF biology.

The management of hydatidiform mole using prophylactic chemotherapy and hysterectomy for high-risk patients decreased the incidence of gestational trophoblastic neoplasia in Vietnam: a retrospective observational study.

The management of hydatidiform mole (HM) and the incidence of post-molar gestational trophoblastic neoplasia (GTN) in Vietnam has not been reported to date. This study aimed to study the incidence of HM and post-molar GTN and identify factors associated with post-molar GTN at a tertiary hospital in Vietnam. Five hundred and eighty-four patients who were treated for HM at Tu Du Hospital between January and December 2010 were included in this study. The mean age and gestational age at the first evacuation were 28.8 years old and 11.0 weeks, respectively. After the initial evacuation and pathological examination, 87 patients who were older than 40 or did not wish to have children underwent a hysterectomy, while the others underwent second curettage. All 472 patients who had human chorionic gonadotropin (hCG) ≥ 100,000 IU/L before treatment received one cycle of methotrexate with folinic acid as prophylactic chemotherapy. The incidence of HM was 11.1 per 1,000 deliveries; 47 patients (8.0%) developed post-molar GTN. Gestational week, hCG level at one week after the first evacuation, and pathological remnants were significantly associated with the development of post-molar GTN. The results of this study suggest that prophylactic chemotherapy and hysterectomy may be useful for high-risk HM patients to reduce post-molar GTN in settings in which the risk of post-molar GTN and loss to follow-up after HM are greater and hCG measurements and appropriate GTN treatments are unavailable. However, future studies on the long-term outcomes and side effects of prophylactic therapies on HM are required.

Beyond Birth Control: Noncontraceptive Benefits of Hormonal Methods and Their Key Role in the General Medical Care of Women.

Contraceptives that contain estrogen and/or progestins are used by millions of women around the world to prevent pregnancy. Owing to their unique physiological mechanism of action, many of these medications can also be used to prevent cancer and treat multiple general medical conditions that are common in women. We performed a comprehensive literature search. This article will describe the specific mechanisms of action and summarize the available data documenting how hormonal contraceptives can prevent ovarian and uterine cancer and be used to treat women with a variety of gynecological and nongynecological conditions such as endometriosis, uterine fibroids, heavy menstrual bleeding, polycystic ovary syndrome, acne, and migraines. Contraceptive methods containing estrogen and progestin can be used for a wide variety of medical issues in women.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) Hull Extract and Active Compounds Inhibit Proliferation of Primary Human Leiomyoma Cells and Protect against Sexual Hormone-Induced Mice Smooth Muscle Hyperproliferation.

Uterine leiomyomas, also known as fibroids, are benign neoplasms of the uterus and have a high incidence rate in women of reproductive age. Hysterectomy or myomectomy is the initial treatment, but fibroids will recur if the patient is still exposed to similar risk factors. Therefore, developing new therapeutic strategies are urgently necessary. In this study, the anti-proliferation effects of each fraction of adlay seeds were evaluated in uterine leiomyomas, and we identified the potential phytochemical compounds. We found that the ethyl acetate fraction of adlay hull (AHE-ea) appeared to be highly efficient in the anti-proliferation of rat uterine leiomyoma ELT3 cells and primary human uterine leiomyoma (hUL) cells. The proliferation of primary human normal uterine smooth muscle (UtSMC) and normal uterine myometrial (hUM) cells were also suppressed by AHE-ea. Two phytosterols, stigmasterol and ß-sitosterol, were identified from AHE-ea fraction. Mice treated with AHE-ea and stigmasterol alone demonstrated reduced diethylstilbestrol/medroxyprogesterone 17-acetate (DES/MPA)-induced uterine myometrial hyperplasia, which is the critical step for the development of leiomyoma. Taken together, our results suggest that the AHE-ea fraction could be considered as a natural plant-based medicine in the prevention or treatment of uterine leiomyoma growth.

Necrobiosis séptica de un fibroma uterino / Septic Necrobiosis of Uterine Fibroma

Los miomas o fibromas, son tumores benignos que aparecen frecuentemente en el útero, y aunque a veces pueden ser asintomáticos, en muchas mujeres son la razón más común de las intervenciones ginecológicas. Algunos autores consideran que la causa es desconocida, otros le dan valor al estímulo estrogénico mantenido o aumentado, que activa los genitoblastos, mesodérmico y celular embrionario que responden a este estímulo. Se presenta el caso de un fibroma uterino complicado con una necrobiosis séptica diagnosticada en una paciente de 63 años de edad. El apoyo diagnóstico con ultrasonografía es de vital importancia en la sospecha diagnóstica de este tipo tumor y sus complicaciones.

Myomas or fibroids are benign tumors that frequently appear in the uterus, and although they can sometimes be asymptomatic, in many women they are the most common reason for gynecological interventions. Some authors consider that the cause is unknown. Others give value to the maintained or increased estrogenic stimulus, which activates the embryonic cell, mesodermal and genitoblasts that respond to this stimulus. We present the case of a complicated uterine fibroid with a septic necrobiosis diagnosed in a 63-year-old patient. Ultrasonography is of vital importance in the diagnosis when there is suspicion of this type of tumor and its complications.

Conhecendo a aderência das mulheres ao exame de câncer de colo de útero / Conociendo la fidelidad de las mujeres al examen de cáncer de cuello de útero / Recognizing the loyalty by women to cervical cancer screening

Introdução: Dentre os tipos de câncer, o cervico-uterino é o que apresenta um dos mais elevados potenciais para prevenção e cura. Métodos: O estudo trata-se de um ensaio comunitário que envolve a intervenção em nível de comunidades, ao invés de indivíduos isolados, sendo usado para avaliar a eficácia e efetividade de intervenções. Objetivo: Este estudo tem como objetivo relacionar os motivos da não adesão ao exame preventivo de câncer de colo de útero e verificar o nível de conhecimento prévio e posterior às palestras. Resultados: Dentre os principais motivos pelos quais as mulheres envolvidas nesse estudo relataram não realizar o exame preventivo regularmente estão o medo do exame, a vergonha de realizar o exame e o desconhecimento de informações. Conclusão: Ainda percebe-se certa resistência na realização dos exames de prevenção do câncer cervico-uterino, sendo esse um grande desafio para as equipes de Estratégias de Saúde da Família

Introducción: Entre los tipos de cáncer, el cáncer cervical es uno del más alto potencial para la prevención y la curación. Métodos: El estudio es una prueba comunitaria que involucra la intervención a nivel de las comunidades, en lugar de individuos aislados, siendo utilizado para evaluar la eficacia y la efectividad de las intervenciones. Objetivo: El objetivo de este estudio es relacionar las razones para la no-fidelidad al examen preventivo para el cáncer de cuello uterino y comprobar el nivel de conocimiento previo y posterior a las conferencias. Resultados: Entre las principales razones aportadas por las mujeres que participaron en este estudio, se destaca el miedo como causa principal de no realizar el examen preventivo regular. También la vergüenza de realizar el examen y, además, la falta de información. Conclusión: Existe cierta resistencia en la realización de los exámenes para la prevención del cáncer cervico-uterino, siendo este un gran reto para los equipos de la Estrategia de Salud de la Familia

Introduction: Among the types of cancer, cervical cancer is one of the highest potential for prevention and cure. Methods: The study is a community test that involves the intervention at the level of communities, instead of isolated individuals, being used to evaluate the efficacy and effectiveness of interventions. Objective: The objective of this study is to relate the reasons for non-loyalty to preventive exam for cancer of the cervix and check the level of prior knowledge and later the lectures. Results: Among the main reasons why women involved in this study reported not to perform the preventive exam regularly are the fear of examination, the shame of performing the examination and the lack of information. Conclusion: Although there is some resistance in the carrying out of examinations for the prevention of cervical-uterine cancer, this being a great challenge for the teams of the Family Health Strategies

The effect of history of abnormal pap smear or preceding HPV infection on the humoral immune response to Quadrivalent Human Papilloma virus (qHPV) vaccine in women with systemic lupus erythematosus.

OBJECTIVE: To determine if natural human papillomavirus (HPV) infection would induce an anamnestic response to quadrivalent (qHPV) vaccine in women with Systemic Lupus Erythematosus (SLE). METHODS: Thirty four women (19-50 years) with mild to moderate and minimally active or inactive SLE received standard qHPV vaccine. Neutralizing antibody titers to HPV 6, 11, 16 and18 were evaluated pre- and post- vaccine using HPV competitive Luminex Immunoassay. For each HPV type, logistic regressions were performed to explore the relationship between a positive titer at baseline with their final geometric mean titer and with the rise in titer. Fisher's Exact Test was used to assess the association of at least one positive HPV antibody test at baseline and history of abnormal pap. RESULTS: History of abnormal pap smear/cervical neoplasia occurred in 52.9%. Baseline anti HPV antibody titers: 21% = negative for all 4 HPV types, 79% = positive for ≥1 of the HPV types. Statistical analysis showed: those with a history of abnormal pap smear/cervical neoplasia were likely to have a positive anti-HPV antibody result pre-vaccine to ≥ 1 of the 4 types, p = 0.035 Fisher's Exact Test. In general, HPV exposed women showed higher post vaccine GMTs than HPV unexposed women with higher point estimates. However, when examining the rise in titers using logistic regression, there was no evidence of an anamnestic response. CONCLUSION: Prior HPV infection and cervical neoplasia in SLE are linked with no anamnestic response to HPV vaccine. This supports not checking HPV-antibodies pre-vaccine. Women with SLE should be vaccinated for HPV.

Cancer Risk-Reducing Opportunities in Gynecologic Surgery.

This review article discusses cancer risk-reducing opportunities in gynecologic surgery. We cover strategies to reduce ovarian and uterine cancer risk by presenting general practice guidelines and expanding on the literature behind clinical decision points. We address populations of women at increased hereditary risk and those at population risk. We specifically discuss risk-reducing salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, concomitant hysterectomy, opportunistic salpingectomy, bilateral tubal ligation, and hysterectomy. For clinical scenarios in which data are limited or conflicting, we detail the studies on which clinicians' decisions hinge to allow the reader to weigh the available evidence.

Metformin for endometrial hyperplasia.

BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar, OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment. MAIN RESULTS: We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low-quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others.Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37, one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea. AUTHORS' CONCLUSIONS: At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question.

Use of metformin is associated with lower incidence of cancer in patients with type 2 diabetes.

INTRODUCTION: The objective of the study was to assess the influence of metformin on the prevalence of cancer and risk factors for the development of cancer, in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 1063 patients, treated between October 2012 and March 2013 in the Diabetes and Endocrinology Centre in Bydgoszcz, were enrolled in the study. Only patients who were first diagnosed with diabetes and consecutively with cancer were included in the analysis. The final dataset compromised data from 1028 patients with type 2 diabetes, in whom retrospective analysis of the association between the occurrence of cancer and treatment with or without metformin was performed. Demographic data, medical history, physical assessment, diabetes history, diabetes complications, concomitant medication, and additional examination results were compared between two groups: those with cancer and those without cancer. Data were analysed using Student's t-test, Chi-square test with Yates' continuity correction, and multiple logistic regression. RESULTS: The most commonly observed cancer was breast cancer (24 patients; 22.5%), followed by uterine cancer (15 patients; 13.6%). Of the 75 diabetic patients with a cancer diagnosis, 18.7% were treated with metformin; of the 953 patients without cancer, 38% received metformin. Analysis of probability of cancer occurrence using Kaplan-Meier curves showed that the probability of cancer development was higher in groups of patients who were not treated with metformin (p = 0.006). CONCLUSIONS: Metformin treatment reduces the risk of cancer in type 2 diabetes patients.

Risk of uterine cancer for BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Whether BRCA1 and BRCA2 mutation carriers have a clinically relevant elevated risk of uterine cancer has implications for risk-reducing surgery. AIM: This multicentre, prospective cohort study assessed uterine cancer risk for mutation carriers compared with the general population. METHODS: Eligible mutation carriers were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) cohort study, had a uterus present and no history of uterine cancer at cohort entry. Epidemiological, lifestyle and clinical data were collected at cohort entry and updated three-yearly. Cancer events were verified using pathology reports. Follow-up was censored at death or last contact. Relative risk of uterine cancer was estimated using the standardised incidence ratio (SIR), with the expected number of cases determined using population-based data for Australia. RESULTS: Of 1,111 mutation carriers in kConFab, 283 were excluded due to prior hysterectomy (N = 278), prior uterine cancer (N = 2) or being non-residents (N = 3). After a median follow-up of 9.0 years, five incident uterine cancers were reported in the 828 eligible women (419 had prior breast cancer and 160 had prior tamoxifen use), compared to 2.04 expected (SIR = 2.45; 95% confidence interval [CI]: 0.80-5.72; P = 0.11). In 438 BRCA1 mutation carriers and 390 BRCA2 mutation carriers, three and two incident cases of uterine cancer were reported, respectively, compared to 1.04 expected (SIR = 2.87; 95% CI: 0.59-8.43; P = 0.18) and 0.99 expected (SIR = 2.01; 95% CI: 0.24-7.30; P = 0.52), respectively. All cases were endometrioid subtype, International Federation of Gynaecology and Obstetrics stage I-II disease. No serous uterine cancers were reported. CONCLUSIONS: Our findings are consistent with those from most other reports and do not support routine risk-reducing hysterectomy for BRCA1 and BRCA2 mutation carriers.