Diet in Prevention and Treatment of Endometriosis: Current State of Knowledge.

PURPOSE OF REVIEW: Endometriosis (EM) is a chronic gynecological disease that affects about 10% of women worldwide. It is characterized by the implantation of endometrial cells at ectopic sites. The most common symptom of EM is painful menstruation, which can often lead to chronic pelvic pain that significantly worsens the quality of life. Because some disease-related processes, such as inflammation, hormonal activity, menstrual cycle, or prostaglandin metabolism, can be modified by diet, nutrition may have a significant impact on development and treatment of EM. The purpose of this article was to overview the current knowledge regarding the dietary management of endometriosis. RECENT FINDINGS: The attention of researchers has so far concentrated mainly on the role of nutrition in the risk of developing EM, while less attention has been paid to examining the use of diet in the treatment of the disease. Current studies focus primarily on various dietary components that have antiproliferative, anti-inflammatory, antioxidant, analgesic, and estrogen-lowering properties. Exploring different ways of coping with endometriosis can make a significant contribution to improving the quality of life of women at risk or diagnosed with EM.

Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

Proposal for targeted, neo-evolutionary-oriented, secondary prevention of early-onset endometriosis and adenomyosis. Part I: pathogenic aspects.

The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until the pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, and prolonged periods of lactational amenorrhoea. For hundreds of thousands of years, menstruators experienced few ovulatory cycles, even though they were genetically adapted to ovulate and menstruate every month. In the post-industrial era, the age at menarche gradually declined, the age at first birth progressively increased, and breastfeeding became optional and often of short duration. This created a mismatch between genetic adaptation and socio-environmental evolution, so that what was initially a probable reproductive advantage subsequently contributed to increased susceptibility to diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial and breast cancer and, hypothetically, also those associated with the number of ovulatory menstruations, such as endometriosis and adenomyosis. The incidence of endometriosis shows a steep and progressive increase around the age of 25 years, but given the consistently reported delay in diagnosis, the actual incidence curve should be shifted to the left, supporting the possibility that the disease has its roots in adolescence. This raises the question of whether, from an evolutionary point of view, anovulation and amenorrhoea should not still be considered the physiological state, especially in the postmenarchal period. However, an increase in the frequency of endometriosis in recent decades has not been demonstrated, although this deserves further epidemiological investigation. In addition, as endometriosis occurs in a minority of individuals exposed to retrograde menstruation, other important pathogenic factors should be scrutinised. Research should be resumed to explore in more detail the transtubal reflux of not only blood, but also endometrial cells, and whether they are systematically present in the peritoneal fluid after menstruation. If repetitive ovulatory menstruation during the early reproductive years is shown to increase the risk of endometriosis and adenomyosis development and progression in susceptible individuals, hormonal interventions could be used as secondary prevention in symptomatic adolescents.

Atorvastatin exerts dual effects of lesion regression and ovarian protection in the prevention and treatment of endometriosis.

Endometriosis is a frequent, chronic, estrogen-dependent and inflammatory gynecological disease leading to pain and infertility. Clinical and metabolic studies reveal that patients with endometriosis are susceptible to hyperlipemia and lipid dysfunction, putting them at ascending risk of cardiovascular diseases. Statins constitute a group of cholesterol-lowering drugs with pleiotropic effects. A plethora of researches have proved their ability to inhibit the growth of ectopic lesions in endometriosis. However, concerns exist about their possible adverse effects on ovarian function. This study aimed to investigate the possible effect of atorvastatin on the ovarian endocrine function and fertility capacity in the prevention and treatment of endometriosis. Here, 5 mg/kg atorvastatin was intraperitoneally injected to the endometriosis mice once a day for consecutive fourteen days during and after the development of endometriotic implants. The results indicated that atorvastatin not only led to regression of the ectopic lesions, but also caused no discernible harm to the ovary for both the preventive and the therapeutic models. In addition, it elicited a protective effect on the ovarian reserve and fertility possibly by reducing inflammation in the ovary. Hence, atorvastatin could be a promising drug for endometriosis prevention and treatment.

Endometriosis: «Nivel de conocimiento y expectativas de formación específica entre profesionales especialistas en medicina de familia y comunitaria y matronas en atención primaria en la isla de Gran Canaria» / Endometriosis: “Level of knowledge and expectations of specific training among primary care doctors and midwives on the island of Gran Canaria, Spain”

Objetivo: Analizar el nivel de conocimiento entre profesionales sanitarios de atención primaria sobre endometriosis e identificar sus necesidades formativas en esta materia. Diseño: Estudio descriptivo realizado en atención primaria del Área de Salud de Gran Canaria, mediante cuestionario online anónimo. Resultados: Ciento diecinueve especialistas en medicina de familia y comunitaria y 37 matronas respondieron el cuestionario. El 54,6% de profesionales médicos y el 67,6% de matronas consideran escaso su conocimiento sobre endometriosis. Menos del 50% de profesionales conoce la guía de atención a las mujeres con endometriosis en el Sistema Nacional de Salud. Los síntomas más frecuentes relacionados con endometriosis son: dismenorrea moderada/severa, dolor pélvico crónico, esterilidad. Los menos relacionados son los digestivos y las alteraciones urinarias catameniales. Un 80% de profesionales médicos señalan como menor de 10 el número anual de pacientes en las que piensan que puedan tener endometriosis y menos de 20 para el 75% de matronas. El 40% de profesionales médicos trataría a una paciente con solo dismenorrea y sin planes de gestación con anticonceptivos orales; el 8% considera que el dolor con la menstruación es algo común. El 25% de profesionales especialistas en medicina de familia y comunitaria señalan la terapia de larga duración con antiinflamatorios no esteroideos como tratamiento de primera línea. Menos del 25% de ellos derivarían al especialista en Ginecología con solo sospechar endometriosis. Mayoritariamente los profesionales manifiestan interés en mejorar su formación en endometriosis. El 94,6% de las matronas consideran que tienen un papel estratégico en el manejo de pacientes con endometriosis. Conclusión: La demora en el diagnóstico de la endometriosis se debe en parte al desconocimiento de la enfermedad. Los profesionales de atención primaria constituyen la primera línea de atención sanitaria.(AU)

Objective: To analyze the level of knowledge of endometriosis in primary care doctors and midwives and to identify their training needs in this area. Design: Descriptive study conducted in the primary care services of the Health Area of Gran Canaria, through an anonymous online questionnaire. Results: One hundred and nineteen doctors and 37 midwives completed the questionnaire; 54.6% of doctors and 67.6% of midwives considered that their knowledge about endometriosis was poor. Less than 50% of healthcare professionals knew the National System of Health's guidelines for the management of women with endometriosis. Symptoms most frequently associated to endometriosis included: moderate/severe dysmenorrhea, chronic pelvic pain and sterility. Less frequently related ones included: digestive symptoms and catamenial urinary disorders; 80% of doctors suspected endometriosis in <10 women per year; 75% of midwives suspected this condition in <20 women per year; 40% of doctors would prescribe oral contraceptives to patients with dysmenorrhea who were not planning pregnancy; 8% of doctors considered that menstruation-associated pain was common. Medical therapy was the most frequently chosen first-line treatment; 25% of doctors would choose long-term NSAIDs therapy as a first-line treatment; less than 25% of them would refer a patient to the Gynecology service only for suspected endometriosis. Most health professionals expressed their interest in improving their knowledge about endometriosis; 94.6% of midwives considered that they played a strategic role in the identification and management of patients with endometriosis. Conclusion: Delays in the diagnosis of endometriosis are partially due to ignorance of the disease. Primary care professionals constitute the first line of health care. In this context, it is essential to develop specific training strategies, which would be welcome by health professionals.(AU)

The Protective Effect of Breastfeeding and Ingesting Human Breast Milk on Subsequent Risk of Endometriosis in Mother and Child: A Systematic Review and Meta-Analysis.

Background: Endometriosis is a chronic and debilitating disease characterized by ectopic, endometrium-like tissue outside the uterine cavity. Objective: The current meta-analysis was conducted to evaluate the effect of breastfeeding and ingesting human breast milk on the subsequent risk of endometriosis. Materials and Methods: The English and Persian databases were systematically searched in accordance with the Mesh browser keywords and free-text words until March 12, 2022. The Newcastle-Ottawa was used to evaluate the quality of the included studies. Publication bias was assessed using Begg's and Egger's tests, and funnel plot. The heterogeneity of studies was evaluated using I2 statistics. Results of the random-effects meta-analysis were presented using odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 18 articles with 10,994 subjects were included in the meta-analysis. Overall, the pool estimates show that breastfeeding (OR = 0.79, 95% CI: 0.71-0.88, I2 = 89%) and ingesting human breast milk (OR = 0.67, 95% CI: 0.50-0.83, I2 = 84.5%) have significantly a protective effect on the risk of endometriosis. Conclusion: Our findings confirm an inverse association between endometriosis risk and ingesting human breast milk, and breastfeeding. Therefore, the importance of breastfeeding for both mother and child should be considered by policymakers and health care providers.

Efficacy of Post-Operative Medication to Prevent Recurrence of Endometrioma: Cyclic Oral Contraceptive (OC) After Gonadotropin-Releasing Hormone (GnRH) Agonist Versus Dienogest.

BACKGROUND: There are several medical treatment options for endometrioma. Progestin, especially dienogest, is an effective drug for preventing recurrence of endometrioma after surgery. Additionally, oral contraceptive (OC) use after conservative surgery has been reported to reduce significantly the risk of endometrioma recurrence. The aim of this study was to compare the long-term effects of gonadotropin-releasing hormone (GnRH) agonist followed by OC to those of dienogest alone to prevent recurrence of endometrioma after laparoscopic surgery. METHODS: A retrospective cohort study was performed on patients who underwent conservative laparoscopic surgery for endometrioma between January 2000 and December 2020, in the Endometriosis Clinic, Department of Gynecology, Samsung Medical Center. A total of 624 patients who received medical treatment at least six months after laparoscopic conservative surgery for endometrioma was included. Among them, 372 patients used OC after GnRH agonist therapy, and 252 patients used dienogest. Within the OC group, 148 used a 21/7 regiment and 224 used a 24/4 regimen. A cumulative endometrioma recurrence curve was presented using the Kaplan-Meier method to compare the recurrence of those groups. RESULTS: The cumulative recurrence rate of endometrioma for 60 months was 2.08% (n = 4) in the OC after GnRH agonist group and 0.40% (n = 1) in the dienogest group. There was no statistical difference in cumulative recurrence of endometrioma between the two groups. In subgroup analysis, the cumulative recurrence rate of endometrioma over 60 months was 4.21% (n = 2) in the 21/7 OC group and 1.09% (n = 2) in the 24/4 OC group and showed no significant difference. CONCLUSION: Long-term use of OC after GnRH agonist as well as that of dienogest treatment are effective postoperative medical therapies for preventing endometrioma recurrence. Thus, the choice of regimen can be individualized or used interchangeably depending on patient condition, need for contraception, and compliance with drug therapy.

SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell via Balancing ERα and PR Signals.

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation. Methods: The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis. Results: Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression. Conclusion: Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.

Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery - A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. DATA SOURCES: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence. TABULATION, INTEGRATION, AND RESULTS: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls. CONCLUSION: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.

Overview of the Effect of Complementary Medicine on Treating or Mitigating the Risk of Endometriosis.

OBJECTIVE: Endometriosis is a hormone-dependent chronic inflammatory disease with symptoms such as pelvic pain, which affect the physical, emotional, and social health of women in reproductive age. The current overview article aims to explore the effect of complementary medicine on the treatment or in mitigating the risk of endometriosis. METHODS: This is an overview article done in Iran. Two separate researchers systematically searched 3 databases (Medline, Scopus, and Cochrane Central Register Trials) until September 2020. The methodological quality of each study was assessed using the assessment of multiple systematic reviews (AMSTAR) tool. RESULTS: The results of two reviews suggested that physical activity, tobacco smoking, diet, coffee and caffeine intake had no effect on mitigating the risk of endometriosis or improving its treatment, but acupuncture successfully reduced pain and related marker (serum CA-125) levels. CONCLUSION: As endometriosis is an annoying disease with many complications and is hard to diagnose and treat, related studies in complementary medicine can help patients with endometriosis. Based on the relevant literature review, among the complementary medicine available for the treatment or to mitigate the risk of endometriosis, only acupuncture seems to alleviate the pain of endometriosis.

OBJETIVO: A endometriose é uma doença inflamatória crônica hormono-dependente com sintomas como dores pélvicas, que afetam a saúde física, emocional e social de mulheres em idade reprodutiva. O presente artigo de visão geral tem como objetivo explorar o efeito da medicina complementar no tratamento ou na mitigação do risco de endometriose. MéTODOS: Trata-se de um artigo de visão geral feito no Irã. Dois pesquisadores separados pesquisaram sistematicamente 3 bancos de dados (Medline, Scopus e Cochrane Central Register Trials) até setembro de 2020. A qualidade metodológica de cada estudo foi avaliada usando a ferramenta avaliação da qualidade dos relatos de revisão sistemática (AMSTAR, na sigla em inglês). RESULTADOS: Os resultados de duas revisões sugeriram que atividade física, tabagismo, dieta, consumo de café e cafeína não tiveram efeito na redução do risco de endometriose ou na melhoria do tratamento, mas a acupuntura reduziu com sucesso a dor e os níveis de marcadores relacionados (CA-125 sérico). CONCLUSãO: Como a endometriose é uma doença incômoda, com muitas complicações e de difícil diagnóstico e tratamento, estudos relacionados em medicina complementar podem ajudar pacientes com endometriose. Com base na revisão da literatura relevante, entre os medicamentos complementares disponíveis para o tratamento ou risco de endometriose, apenas a acupuntura parece aliviar a dor da endometriose.

Overview of the Effect of Complementary Medicine on Treating or Mitigating the Risk of Endometriosis / Visão geral do efeito da medicina complementar no tratamento ou mitigação do risco de endometriose

Abstract Objective Endometriosis is a hormone-dependent chronic inflammatory disease with symptoms such as pelvic pain, which affect the physical, emotional, and social health of women in reproductive age. The current overview article aims to explore the effect of complementary medicine on the treatment or in mitigating the risk of endometriosis. Methods This is an overview article done in Iran. Two separate researchers systematically searched 3 databases (Medline, Scopus, and Cochrane Central Register Trials) until September 2020. The methodological quality of each study was assessed using the assessment of multiple systematic reviews (AMSTAR) tool. Results The results of two reviews suggested that physical activity, tobacco smoking, diet, coffee and caffeine intake had no effect on mitigating the risk of endometriosis or improving its treatment, but acupuncture successfully reduced pain and related marker (serum CA-125) levels. Conclusion As endometriosis is an annoying disease with many complications and is hard to diagnose and treat, related studies in complementary medicine can help patients with endometriosis. Based on the relevant literature review, among the complementary medicine available for the treatment or to mitigate the risk of endometriosis, only acupuncture seems to alleviate the pain of endometriosis.

Resumo Objetivo A endometriose é uma doença inflamatória crônica hormono-dependente com sintomas como dores pélvicas, que afetam a saúde física, emocional e social de mulheres em idade reprodutiva. O presente artigo de visão geral tem como objetivo explorar o efeito da medicina complementar no tratamento ou na mitigação do risco de endometriose. Métodos Trata-se de um artigo de visão geral feito no Irã. Dois pesquisadores separados pesquisaram sistematicamente 3 bancos de dados (Medline, Scopus e Cochrane Central Register Trials) até setembro de 2020. A qualidade metodológica de cada estudo foi avaliada usando a ferramenta avaliação da qualidade dos relatos de revisão sistemática (AMSTAR, na sigla em inglês). Resultados Os resultados de duas revisões sugeriram que atividade física, tabagismo, dieta, consumo de café e cafeína não tiveram efeito na redução do risco de endometriose ou na melhoria do tratamento, mas a acupuntura reduziu com sucesso a dor e os níveis de marcadores relacionados (CA-125 sérico). Conclusão Como a endometriose é uma doença incômoda, com muitas complicações e de difícil diagnóstico e tratamento, estudos relacionados em medicina complementar podem ajudar pacientes com endometriose. Com base na revisão da literatura relevante, entre os medicamentos complementares disponíveis para o tratamento ou risco de endometriose, apenas a acupuntura parece aliviar a dor da endometriose.

Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study.

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC-MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.

The effectiveness of Rutin for prevention of surgical induced endometriosis development in a rat model.

Apoptosis and antioxidant mechanisms are pathways for the treatment of endometriosis (Endo). Rutin (Rtn) is an antioxidant flavonol that induces apoptosis. This study, for first time, was conducted to evaluate the effects of rutin on Endo through apoptosis and antioxidant mechanisms. The experimental Endo was induced in 24 rats and then the animals were subdivided into Endo-sole, 3000 and 6000 µg/kg rutin (Rtn-3000 and Rtn-6000) and vitamin C groups. After 4 weeks, the expression of Bcl2, Bax, anti Pro Caspase-9, cleaved Caspase-9, pro PARP, pro Cleaved PARP, Pro PARP, pro mTOR and mTOR were assessed by western blotting technique. The protein concentrations of malondialdehyde (MDA), total antioxidant capacity, and super oxide dismutase and gutathione peroxidase were also evaluated. TUNEL staining was also used for the detection of apoptosis. Caspase-9 and concentration of antioxidants were higher in the treated groups compared to Endo-sole group (P < 0.05). The results also showed that rutin decreased the expression of Bcl2 and MDA concentration (P < 0.05). The results for TUNEL staining showed that the animals treated with Rtn-6000 and vitamin C showed higher apoptosis. Rutin induces apoptosis by the expression of Bcl-2, Bax and caspase and also antioxidant activity by increasing antioxidants concentrations.

Prepregnancy antiinflammatory diet in pregnant women with endometriosis: The Japan Environment and Children's Study.

OBJECTIVES: Increased risk of preterm birth (PTB) in women with endometriosis is considered to be associated with chronic inflammatory conditions. Accordingly, we hypothesized that a prepregnancy antiinflammatory diet is a potential form of preconception care for preventing PTB in women with endometriosis and conducted this study to investigate the correlation of a prepregnancy antiinflammatory diet with obstetric outcomes in this patient population. METHODS: We used singleton pregnancy data from the Japan Environment and Children's Study involving live births from 2011 to 2014. Individual meal patterns before pregnancy, derived through food frequency questionnaires, were used to calculate the Dietary Inflammatory Index. Participants were categorized according to Dietary Inflammatory Index quintiles (Q1 and Q5 were the most proinflammatory and antiinflammatory groups, respectively), and a multiple logistic regression model was used to estimate the effect of the antiinflammatory diet on PTB before 37 or 34 wk and on low birth weight (LBW) <2500 or 1500 g. RESULTS: In women who did not undergo assisted reproduction, significantly reduced risk was found in the Q5 group for both PTB at <34 wk significantly decreased (adjusted odds ratio, 0.25; 95% confidence interval, 0.07-0.83) and low birth weight <1500 g (adjusted odds ratio, 0.07; 95% confidence interval, 0.01-0.60). CONCLUSIONS: This study suggests a distinct effect of an antiinflammatory diet on more severe obstetric outcomes, specifically PTB before 34 wk and low birth weight <1500 g, for women with endometriosis. Preconception lifestyle can improve perinatal mortality and morbidity among these women.

[Menstrual disorders: what we know about dietary-nutritional therapy]. / Desórdenes menstruales: lo que sabemos de la terapia dietética-nutricional.

INTRODUCTION: The reproductive age of a woman comprises a large part of her life. Suffering from menstrual disorders, such as dysmenorrhea, endometriosis and premenstrual syndrome (PMS), can have serious implications in the lives of those suffering them, so it is important to diagnose these problems and treat them in the most appropriate way. In the diagnosis of these problems it is important to carry out a rigorous medical history, in which a complete menstrual history is collected. Analgesic and hormonal pharmacological treatment, dietary therapy, surgery or alternative therapies may be included within the approach of these conditions. Regarding diet, this seems to be an important modulating factor, without having studied with sufficient scientific rigor the real effect it causes in women suffering from menstrual disorders. It is advisable to study each case individually and adapt the dietary-nutritional therapy. In endometriosis, for example, any additional problems such as fertility problems or immune diseases must be considered. In general, it is recommended to follow a healthy eating pattern, in which fresh unprocessed foods predominate, and avoid those rich in refined carbohydrates or fats, salt, alcohol and stimulating beverages. The efficacy of food supplements requires further research, although the positive effect of evening primrose oil on PMS appears to be a proven fact.

INTRODUCCIÓN: La etapa fértil de la mujer comprende gran parte de su vida. El padecimiento de desórdenes menstruales, como dismenorrea, endometriosis y síndrome premenstrual (SPM), puede suponer graves implicaciones en la vida de las que lo sufren, por lo que es importante diagnosticar y tratarlos del modo más adecuado. En la diagnosis es importante realizar una rigurosa historia clínica donde se recoja una anamnesis menstrual completa. Dentro del abordaje de estas afecciones pueden incluirse el tratamiento farmacológico analgésico y hormonal, la dietoterapia, cirugía o prácticas alternativas. Aunque la alimentación parece ser un factor modulador importante, no se ha estudiado con suficiente rigurosidad científica el efecto real que provoca en mujeres con alteraciones menstruales. Se aconseja estudiar cada caso de manera individual y adaptar la pauta dietética-nutricional. En endometriosis, por ejemplo, deberá considerarse de manera adicional si existen problemas de fertilidad o enfermedades de índole inmunitario. En líneas generales, se recomienda seguir un patrón de alimentación saludable, en el que predominen los alimentos frescos no procesados, y evitar los ricos en hidratos de carbono refinados o grasas, sal, alcohol y bebidas estimulantes. La eficacia de los suplementos alimentarios requiere mayor investigación, aunque el efecto positivo del aceite de onagra en el SPM parece ser un hecho probado.

Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis.

BACKGROUND: The efficacy of hormonal regimens for the prevention of endometrioma recurrence in women who have undergone conservative surgery is still controversial. OBJECTIVE: To compare the efficacy of different hormonal regimens in this context and to rank them. SEARCH STRATEGY: MEDLINE and Scopus databases were searched through January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cohorts, comparing the effect of any pair of interventions (i.e. cyclic oral contraceptives [OC], continuous OC, gonadotropin-releasing hormone agonist [GnRHa], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNG-IUS] and expectant management) on endometrioma recurrence were selected. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA) and ranked in descending order. MAIN RESULTS: Six RCTs (675 patients) and 16 cohorts (3089 patients) were included. NMA of the RCTs involving expectant management, cyclic OC, continuous OC, GnRHa and GnRHa + LNG-IUS, showed that all hormonal regimens had a nonsignificant lower risk of endometrioma recurrence compared with expectant management. NMA of the cohorts involving expectant, cyclic OC, continuous OC, GnRHa, DNG, LNG-IUS, GnRHa + OC, and GnRHa + LNG-IUS indicated that LNG-IUS, DNG, continuous OC, GnRHa + OC and cyclic OC had a significantly lower risk of endometrioma recurrence than expectant management. LNG-IUS was ranked highest, followed by DNG and GnRHa + LNG-IUS. Long-term use of hormonal treatment either OC or progestin had a significantly lower risk of endometrioma recurrence than expectant treatment. CONCLUSION: In the NMA of RCTs, there was no evidence supporting hormonal treatment for postoperative prevention of endometrioma recurrence. This was at odds with the cohort evidence, which found the protective effect of OC and progestin regimens, especially long-term treatment. Large-scale RCTs of these agents are still required. TWEETABLE ABSTRACT: Hormonal regimens given as long-term treatment tend to reduce risk of endometrioma recurrence after conservative surgery.

Chinese herbal medicine for previous cesarean scar defect: A protocol for systematic review and meta-analysis.

BACKGROUND: Previous cesarean scar defect (PCSD) is a gynecological disease that can cause bleeding after intercourse, prolonging menstrual period, intermenstrual bleeding, dysmenorrhea, and even lead to infertility. Chinese herbal medicine plays an important role in the treatment of gynecological diseases in China and East Asia. This study aims to assess the efficacy and safety of Chinese herbal medicine for PCSD. METHODS: We search the following databases: PubMed, the Cochrane Library, Chinese Biomedical Literature Database (CB), Chinese Science and Technique Journals Database (VIP), EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and the Wanfang Database. Other sources will also be searched like Google Scholar and gray literature. All databases mentioned above are searched from the start date to the latest version. Randomized controlled trials will be included which recruiting PCSD participants to assess the efficacy and safety of Chinese herbal medicines against controls (placebo or other therapeutic agents). Primary outcomes will include the size of PCSD, menstrual cycle, menstrual phase, menstrual volume, duration of disease, security index. Two authors will independently scan the searched articles, extract the data from attached articles, and import them into Endnote X8 and use Microsoft Excel 2013 to manage data and information. We will assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the participation of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. The meta-analysis in this review will use RevMan 5.3 software. RESULTS: The study aims to evaluate the efficacy and safety of the treatment that Chinese herbal medicine for PCSD. CONCLUSION: This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice. INPLASY REGISTRATION NUMBER: INPLASY202090080.

Possible involvement of crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1.

BACKGROUND: The density and the activity of mast cells are associated with endometriosis. However, the role of mast cells on the pathogenesis of endometriosis remains unclear. Our study aims to investigate whether endometrial cells interact with mast cells and the involvement of their crosstalk in the development of endometriosis. METHODS: The transwell assay was applied to investigate the effect of mast cells on the migratory ability of human primary endometrial cells. Mast cells were cocultured with endometrial epithelial and stromal cells respectively and total RNAs were isolated and subjected to mRNA sequencing. Next, the transwell assay, CCK-8, and tube formation were applied to study the role of CCL8 on the endometrial and endothelial cells in vitro. The mouse model was also established to confirm the role of CCL8 in the development and angiogenesis of endometriosis. RESULTS: CCL8 was up-regulated in mast cells when cocultured with endometrial cells. CCL8 was highly expressed in the ectopic endometrium and the serum of patients with endometriosis. CCL8 promoted the migratory ability of endometrial epithelial and stromal cells and increased the proliferation, migration, and tube formation of endothelial cells. CCR1, the receptor of CCL8, was over-expressed in the ectopic endometrium and colocalized with blood vessels in ovarian endometriomas. The inhibition of CCR1 suppressed the development and angiogenesis of endometriosis in vivo. CONCLUSION: The crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1 was demonstrated, thereby providing a new treatment strategy for endometriosis.

Immunomodulation inhibits the development of endometriosis in rats.

Endometriosis, the presence of ectopic endometrium, has an unclear etiology and is commonly associated with endocrine, genetic, and immunological imbalance. This study determined whether immunomodulation by the RESAN vaccine could alter the potentially pathogenic gene expression profiles in the cells of the eutopic endometrium in an animal model of endometriosis. Preventing these changes could inhibit the early development of the illness and support the success of surgical treatment. Wistar rats were divided into three groups: prophylaxis (vaccinated before ectopic endometrium implantation, n = 23), therapeutic (vaccinated at the time of the ectopic excision, n = 23) and control (n = 10). During the first laparotomy, autotransplantation of the endometrium to the peritoneum was performed in the prophylaxis and therapeutic groups. The second laparotomy was carried out three months later in all groups to examine endometriotic foci and adhesions. Suspected endometriosis foci were removed. Three months later, the third laparotomy was performed in all animals, followed by suspected foci excision. Fragments of the eutopic endometrium were collected from all animals during the first and third laparotomies. All samples were analysed by real-time PCR to assess the expression of Bcl2, Bax, Bax/Bcl2 ratio, Mki67, and Tert genes. Endometrial foci were found in abdominal peritoneum at the second laparotomy in 1 animal in the prophylaxis group, compared to 16 animals in the therapeutic group. The prophylaxis group showed a high expression of Bax while the therapeutic group showed high expression of Bax, Tert and Mki67 genes. Additional analysis revealed that throughout the six months of the experiment, the expression of the Bax, Tert, and Mki67 genes decreased significantly in the prophylaxis group, Mki67 gene expression decreased in the therapeutic group, and Tert, Mki67, and Bcl2 gene expression decreased in the control group. The results indicate that immunomodulation affects the balance between apoptosis and proliferation in the eutopic endometrium and may prevent the onset and recurrence of endometriosis.