Endometriosis-associated Symptoms Research Articles

The impact of the microbiota-gut-brain axis on endometriosis-associated symptoms: mechanisms and opportunities for personalised management strategies.

Endometriosis is a chronic inflammatory condition affecting one in 10 women and those assigned female at birth, defined by the presence of endometrial-like tissue outside the uterus. It is commonly associated with pain, infertility, and mood disorders, and often comorbid with other chronic pain conditions, such as irritable bowel syndrome. Recent research has identified a key role for the microbiota-gut-brain axis in health and a range of inflammatory and neurological disorders, prompting an exploration of its potential mechanistic role in endometriosis. Increased awareness of the impact of the gut microbiota within the patient community, combined with the often-detrimental side effects of current therapies, has motivated many to utilise self-management strategies, such as dietary modification and supplements, despite a lack of robust clinical evidence. Current research has characterised the gut microbiota in endometriosis patients and animal models. However, small cohorts and differing methodology has resulted in little consensus in the data. In this narrative review, we summarise research studies that have investigated the role of gut microbiota and their metabolic products in the development and progression of endometriosis lesions, before summarising insights from research into co-morbid conditions and discussing the reported impact of self-management strategies on symptoms of endometriosis. Finally, we suggest ways in which this promising field of research could be expanded to explore the role of specific bacteria, improve access to 'microbial' phenotyping, and to develop personalised patient advice for reduction of symptoms such as chronic pain and bloating.

Changes in Endometriosis-Associated Symptoms Following Immunization against SARS-CoV-2: A Cross-Sectional Study.

Background: There are many reports about variations in the menstrual cycle after infection with SARS-CoV-2 or vaccination against it. However, data on SARS-CoV-2 infection or vaccination-related changes in menstruation-associated endometriosis-typical symptoms such as dysmenorrhea, dyspareunia, dyschezia, dysuria, and bloating are rare or missing. Methods: This retrospective study was performed as an online survey among employees and students at the University Hospital Ulm, Germany. Changes regarding the presence of mentioned symptoms and after immunization (vaccination and/or infection) were evaluated with the McNemar Test. Additionally, the risk factors associated with these changes and associations between a subjectively perceived general change in menstruation and changes in the symptoms were evaluated. Results: A total of 1589 respondents were included in the final analysis. Less than 4% of respondents reported the occurrence of new symptoms that they had not experienced before immunization. Overall, there was a significant reduction in the presence of dysmenorrhea, back pain, dyschezia, bloating, and dyspareunia after immunization against coronavirus (p < 0.001). Only 2.3% of all participants reported to have been diagnosed with endometriosis. Factors associated with changes in endometriosis-typical symptoms following immunization were body mass index, age, endometriosis, and thyroid disease. Conclusions: Our results provide unique data about a reduction in the incidence of endometriosis-associated symptoms as dysmenorrhea, dyschezia, and dyspareunia after immunization against COVID-19.

Use of the Drospirenone-Only Contraceptive Pill in Adolescents with Endometriosis

Study ObjectiveTo evaluate the efficacy and tolerability of a progestin-only pill containing 4 mg drospirenone (DRSP) as a hormonal therapy for the management of endometriosis-associated symptoms in adolescents and young adults. DesignRetrospective cohort study. MethodsA retrospective chart review was performed of all adolescents who were prescribed DRSP continuously (without placebo) for treatment of endometriosis at a single pediatric tertiary care center between 2019 and 2022. Electronic medical records were reviewed to obtain demographics and clinical characteristics of the patients. Measured outcomes included symptom resolution and medication discontinuation. The study was deemed IRB exempt. ResultsA total of 61 patients with endometriosis were prescribed DRSP during the study period, with a median age of 18.9 years (SD 2.3). The majority (97%) were laparoscopically confirmed to have endometriosis, and 85% had stage I disease. Before DRSP use, the most common medications trialed were norethindrone (57%) and norethindrone acetate (68%), and 56% had at least one medical contraindication to receiving estrogen-containing therapy. Of those with follow-up, 52% established an absence of bleeding/spotting, and 67% reported less pain at follow-up. One in 4 patients discontinued DRSP during the study period, most commonly due to breakthrough bleeding. ConclusionDRSP is a well-tolerated and effective option for the treatment of endometriosis-associated symptoms in adolescents and young adults.

Pelvic pain symptoms and endometriosis characteristics in relation to oxidative stress among adolescents and adults with and without surgically-confirmed endometriosis.

Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-linked immunosorbent assay, we measured 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in urine samples and corrected for creatinine levels in 434 surgically-confirmed endometriosis participants compared to 605 participants never diagnosed with endometriosis. At enrollment, participants reported details of their pelvic pain symptoms. Linear regression was used to compute geometric mean (GM) creatinine-corrected 8-OHdG levels with 95% confidence intervals (CI) among all participants and those with and without endometriosis separately, adjusting for potential confounders. Interactions by surgically-confirmed endometriosis status were tested by Wald statistics. Results: No trends in 8-OHdG were observed among those with or without endometriosis for severity or frequency of dysmenorrhea, acyclic pelvic pain, dyspareunia or pain with bowel movements. Among endometriosis participants, lower 8-OHdG levels were observed for participants with any white, blue/black, or brown lesions (GM=76.7 versus 82.9 ng/mg; p=0.10), which was primarily driven by lower levels of 8-OHdG for any blue/black lesions (GM=72.8 versus 81.6 ng/mg; p=0.05). Conclusion: While no associations were observed between 8-OHdG and pelvic pain symptoms, future research is needed to assess how other pathways of oxidative damage, e.g. through proteins or lipids, may affect endometriosis-associated symptoms. Additionally, further research is needed to understand differences in oxidative stress among endometriosis lesion sub-phenotypes.

FRI372 Retinoic Acids Attenuate The Endometriotic Cell Proliferation Through A Cell-specific Receptor Isoform

Abstract Disclosure: M. Izawa: None. Y. Azuma: None. F. Taniguchi: None. [Background] Endometriosis has been accepted as an estrogen-dependent, proliferative and inflammatory disease for over two decades, and the hormonal therapy targeting the reduction of estrogen has been employed as the first choice of treatment to reduce the endometriosis-associated symptoms. However, the limitation of therapy is becoming evident. In the hope of overcoming the limitation, we focused on retinoids, which have been known to elicit antiproliferative activity in breast tumors. Retinoic acid receptor (RAR) expression has been known to correlate with estrogen receptor expression. [Objective] As a first step to test the antiproliferative activity of retinoids in endometriotic lesions, we examined the expression profile of the retinoic acid receptor (RAR) in endometriotic cells. We then examined the antiproliferative activity of retinoids and the effect of estrogen on their activity. [Patients] Institutional Review Boards approved this project. We obtained informed consent from all patients. The chocolate cyst lining in the ovaries of patients with endometriosis was the source of endometriotic tissue. [Methods] Endometriotic cells: Stromal cells were collected from endometriotic tissues and used as endometriotic cells throughout the experiment. RAR gene expression: Single-stranded cDNA was prepared and subjected to PCR. Primer sets were designed using sequences in the UCSF genome browser. At the end of PCR cycles, the reaction mixture was subjected to electrophoresis on agarose gel. As an internal control, β-tubulin mRNA expression was assayed in parallel. Cell proliferation: Endometriotic cells were treated with retinoids in the presence or absence of estradiol (E2). All-trans retinoic acid (ATRA) and selective RAR modulators (SRARMs) were used. The number of viable cells was estimated using WST-8 assay. Ki-67 expression: Ki-67 expression was examined by Western blotting. As an internal control, β-tubulin expression was assayed in parallel. [Results] RAR mRNA expression: Transcripts of wild-type RARα, RARβ, RARγ, and their splice variants were demonstrated. These mRNAs were expressed almost at a comparable level: a truncated form of RARα without a DNA binding domain, a truncated form of RARβ without a transactivation domain at the N-terminal, and a form of RARγ with a distinct transactivation domain at N-terminal region. Effect of Retinoic acids on cell proliferation: The cell proliferation rate and Ki-67 expression were downregulated in the presence of ATRA. Among SRARMs tested, a selective RARγ modulator decreased cell proliferation. The antiproliferative activity of ATRA was attenuated in the presence of E2 in some cells.[Conclusion]We tested the antiproliferative activity of retinoids in endometriotic cells. Although the endometriotic cells responded to retinoids, the present finding suggested the diversity of cell types in endometriotic lesions. Presentation: Friday, June 16, 2023

P-320 Change of bone mineral density after long-term use of dienogest with calcium and vitamin D supplementation after surgical treatment of endometrioma

Abstract Study question Does long-term use of dienogest reduce bone mineral density (BMD)? Is ovarian reserve after surgery a risk factor for BMD loss? Summary answer BMD was not significantly changed after long-term use of DNG for up to 8years. In patients with minimal changes, postoperative ovarian reserve were not different. What is known already Dienogest (DNG) is a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms. However, there’re some debates about the bone loss after long-term treatment. Some studies reported the BMD reduction after 2-3 years, however, predictive risk factors for BMD reduction were not found. Hypergonadotropic amenorrhea is well known risk factors for osteoporosis. Research on whether postoperative ovarian function decline is associated with osteoporosis is still lacking. Study design, size, duration This retrospective study were performed with 6180 reproductive-aged women who underwent conservative surgery for endometriomas and received postoperative dienogest (2mg/day) to prevent recurrence in the single center from May 2013 to March 2022. Among them, Sixty nine women who took DNG for more than two years after surgery and followed up BMD were enrolled for this study. Participants/materials, setting, methods Sixty nine women taking DNG for more than 24 months up to 101 months after laparoscopic operation for endometriosis were retrospectively analyzed. Calcium and vitamins were taken as supplements. The changes of BMD were evaluated every year during DNG treatment by using dual energy X-ray absorptiometry. Pain and tumor recurrence were evaluated every three months after operation. For the risk evaluation, age, BMI, tumor size and bilaterality, FSH, estradiol and AMH levels were evaluated. Main results and the role of chance Mean age of enrolled women was 39.64 ± 7.59, and mean BMI was 21.79 ± 3.51 kg/m2. Mean duration of medication was 41.33 ± 17.66 months (24-101 months). Tumor size was 5.35 ± 4.29cm. Preoperative AMH was 2.81 ± 2.07 ng/mL, postoperative AMH was 1.78 ± 2.11 ng/mL, reduction of AMH levels was 1.24 ± 1.26 ng/mL (0.0 - 4.15). Mean BMD level of femur after DNG treatment was 0.8264 ± 0.1201 g/cm2, which was not different compared to baseline (0.8404 ± 0.1194 g/cm2). BMD levels of lumbar spine were not different either after DNG treatment (baseline 0.9411 ± 0.1141 g/cm2, post-treatment 0.9477 ± 0.1346 g/cm2, separately). Only 15% of patients showed minimally decreased BMD at femur (-0.85%), mean femur BMD levels were not statistically different compared those of unchanged BMD group. Although 62.5% of patients showed a decrease in BMD at lumbar spine, mean BMD levels were not statistically different either. Postoperative FSH, estradiol and AMH levels were not significantly different between women who had reduced BMD at both site after long-term DNG use and women who did not. Limitations, reasons for caution As a retrospective study based on existing medical records, other factors that might affect the bone mineral density such as the diet, physical activity could not be assessed. Unfortunately, only a limited number of patients were included in the study as most patients received DNG for less than 2 years. Wider implications of the findings The current study contributes to enrich literature about the advantages of using DNG in a long term to prevent endometriosis recurrence. Trial registration number 2022-07-062

The effect of SARS-CoV-2 BNT162b2 vaccine on the symptoms of women with endometriosis.

PurposeAs the use of the messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) Coronavirus disease 2019 vaccine has grown, reports on menstrual changes have arisen. We aimed to examine menstrual bleeding patterns and endometriosis-associated symptoms after receiving the mRNA BNT162b2 SARS-CoV-2 vaccine in women with endometriosis, as compared to the control group.MethodsThis is a questionnaire-based cross-sectional study including a total of 174 women. The study group included 86 women with a confirmed diagnosis of endometriosis and the control group included 88 women with no diagnosis or suspected diagnosis of endometriosis. Each woman completed a questionnaire on menstrual bleeding patterns and endometriosis-associated symptoms before and after receiving two doses of the BNT162b2 vaccine. Primary outcomes were changes in amount or length of menstrual bleeding, rates of intermenstrual bleeding and worsening in dysmenorrhea in the endometriosis patient group, as compared to the control group. Secondary outcomes included changes in all endometriosis-associated symptoms.ResultsIn our cohort, women with endometriosis were more likely to experience changes in bleeding patterns (women with endometriosis: 39.5%, control group: 31.0%, p = 0.02), and a significant worsening in endometriosis-associated symptoms with an almost 4.3-fold worsening in dysmenorrhea [95% CI 1.9–9.9, p < 0.01] and 5.5-fold odds for any worsening in symptoms in endometriosis patients, as compared to the control group [95% CI 2.7–11.1, p < 0.01].ConclusionIn our cohort, endometriosis was shown to be a significant risk factor for worsening of menstrual symptoms, after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine. Further research is needed to confirm these findings.

Endometriosis-associated Symptoms and Diagnostic Delay: An Online Survey

Background & Objective: The aim of this study was to determine the endometriosis-associated symptoms and diagnostic delay through an online survey.Materials & Methods: A cross-sectional study was conducted in Australia using an online web-based survey. All data were entered into and analyzed using the STATA software (version 14.1). A total of 903 respondents completed an online survey from September 2013 to October 2015.Results: Out of 903, 71.10% were Australians and 28.90% were Non-Australian, with a self-reported diagnosis of endometriosis confirmed by surgery. Out of the participants, 86.5% completed the online survey. Delay in diagnosis was 8.1±6.2 years. There was no difference in the age range (P < /i> = 0.35), mean age of onset of the first symptoms (P < /i> = 0.93), and delay in diagnosis (P < /i> = 0.11) between both groups. Most common endometriosis-related symptoms that all respondents had experienced in their lifetime were period pain (98.1%), fatigue (94%), bloating (90.7%), ovulation pain (88.7%), pelvic pain (87.3%), pain during and before/after sexual activity (82.7%), and heavy bleeding (82.2%). Treatments used by affected women included: pain killers (96%), hormonal medication (84.7%), surgical treatments (84.5%), and delayed fertility (37.1%). Conclusion: Vast similarities in demographics and endometriosis-associated symptoms among the Australian and non-Australian women with endometriosis support the universality of the disease characteristics. Delay in diagnosis of endometriosis is a problem and the reasons for delayed diagnosis must be understood to try to shorten this delay. Besides pain, patients with endometriosis suffer from a variety of other symptoms; hence, any treatment must take into account the most prominent symptoms.

Association between endometriosis and lower urinary tract symptoms

To determine if women with endometriosis experience lower urinary tract symptoms (LUTSs) more often than those without. Cross-sectional analysis at enrollment in a longitudinal cohort. Enrollment at 2 academic hospitals and from the local community. This analysis included 1,161 women with (n = 520) and without (n = 641) surgically confirmed endometriosis who were enrolled in the Women's Health Study: from Adolescence to Adulthood between 2012 and2018. Not applicable. Prevalence of LUTSs, including stress incontinence, urgency and frequency, straining with urination, incomplete bladder emptying, hematuria, dysuria, and bladder pain using standardized questionnaires. The primary outcomes were that women with endometriosis reported the following more often than those without: difficulty passing urine (7.9% vs. 2%; crude odds ratio [OR], 4.14 [95% confidence interval {CI}, 2.19-7.80]; adjusted OR [aOR], 4.31 [95% CI, 2.07-8.95]); still feeling full after urination (18.8% vs. 4.7%; crude OR, 4.73 [95% CI, 3.08-7.25]; aOR, 4.67 [95% CI, 2.88-7.56]); having to urinate again within minutes of urinating (33.1% vs. 17.0%; crude OR, 2.41 [95% CI, 1.83-3.18]; aOR, 2.49 [95% CI, 1.81-3.43]), dysuria (11.7% vs. 4.9%; crude OR, 2.55 [95% CI, 1.62-4.01]; aOR, 2.38 [95% CI, 1.40-4.02]); and pain when the bladder is full (23.0% vs. 4.9%; crude OR, 5.79 [95% CI, 3.82-8.78]; aOR, 6.04 [95% CI, 3.74-9.76]). For the secondary outcomes, among female participants with endometriosis, we observed that the odds of LUTS did not differ by the revised American Society for Reproductive Medicine stage (I/II vs. III/IV) or duration of endometriosis-associated symptoms. Women with surgically confirmed endometriosis were more likely to report LUTS than those without.

Real world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis

Endometriosis is a chronic disease that requires a suitable, lifelong treatment. To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is to date the largest real-world, non-interventional study investigating hormonal management of endometriosis. We describe women’s experiences of endometriosis in the real world by considering their symptoms and the diagnostic process in their healthcare setting. Overall, 27,840 women were enrolled from six European countries via networks of gynecologists or specialized centers. Of these, 87.8% of women were diagnosed based on clinical symptoms; the greatest and lowest proportions of women were in Russia (94.1%) and Germany (61.9%), respectively. Most women (82.8%) experienced at least one of the triad of endometriosis-associated pain symptoms: pelvic pain, pain after/during sexual intercourse, and painful menstrual periods. The most frequently reported endometriosis-associated symptoms were painful periods (61.8%), heavy/irregular bleeding (50.8%), and pelvic pain (37.2%). Women reported that endometriosis impacted their mood; 55.6% reported feeling “down”, depressed, or hopeless, and 53.2% reported feeling like a failure or having let down family/friends. VIPOS broadens our understanding of endometriosis based on real-world data by exploring the heterogeneity of symptoms women with endometriosis experience and the differences in diagnostic approaches between European countries.Trial registration: ClinicalTrials.gov, NCT01266421; registered 24 December 2010. Registered in the European Union electronic Register of Post-Authorisation Studies as number 1613.

Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review

BackgroundEndometriosis is a common benign gynecological disease that has the potential to debilitate due to pain and reduced quality of life. Treatment modalities such as hormones and surgery have limitations and do not treat all dimensions of the problems caused by endometriosis, and physical activity (PA) and exercise have been suggested as alternative treatments. Aim of this study was to perform a systematic review and meta-analysis to assess the effect of PA and exercise on endometriosis-associated symptoms.MethodsEleven databases were searched systematically. Study selection, quality assessment, and data extraction were carried out by two independent researchers in accordance with PRISMA guidelines. Eligibility criteria were women with diagnosed endometriosis receiving an intervention (PA and/or exercise). The primary outcome was pain intensity, but all outcomes were accepted.ResultsThis study screened 1045 citations for eligibility. Four interventional studies were identified, of which one showed fatal design flaws and so was excluded. Three studies, two randomized controlled trials (RCT) and one pre-post study with no control group, involving 109 patients were included in a descriptive synthesis. The interventions included flexibility and strength training, cardiovascular fitness, and yoga, and were performed from one to four times per week for a total duration of 8–24 weeks, with or without supervision. Only one study found improvements in pain intensity. One study showed decreases in stress levels. Due to the heterogeneity of the study outcomes and measures, as well as confounding factors, a quantitative meta-analysis could not be performed.ConclusionThe effect of PA and exercise as treatments for endometrioses-associated symptoms could not be determined due to significant limitations of the included studies. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools.Trial registration numberCRD42021233138.

P–306 Premenopausal women with a diagnosis of endometriosis have a significantly higher prevalence of a diagnosis or symptoms suggestive of restless leg syndrome; prospective cross-sectional study

Abstract Study question Are women who report a previous surgical diagnosis of endometriosis more likely to have a diagnosis or symptoms suggestive of restless leg syndrome (RLS)? Summary answer: Women who reported a prior surgical diagnosis of endometriosis, have a significantly higher prevalence of prior formal diagnosis of RLS or symptoms suggestive of RLS. What is known already Endometriosis and RLS are both chronic conditions that can negatively affect a woman’s quality of life. A higher prevalence of RLS is seen in women and particularly in those who are pregnant, suggesting a possible ovarian hormonal influence. Endometriosis is a common (affecting 1 in 10 women) oestrogen driven gynaecological condition, and the prevalence of RLS in women with symptoms or a diagnosis of endometriosis is unknown. Study design, size, duration This was a prospective, cross-sectional, observational self-completed questionnaire study. Questionnaires were distributed to 650 women under 50 years of age attending the gynaecology out patient’s department at the Liverpool Women’s hospital from October 2017 to January 2018. Participants/materials, setting, methods 584 women returned the voluntary, anonymous questionnaires, which assessed RLS-associated (The International Restless Leg Syndrome Study Group rating scale) and endometriosis-associated (modified-British Society of Gynaecological Endoscopists pelvic pain questionnaire) symptoms. The final dataset included 465 completed questionnaires. Main results and the role of chance The overall response rate for this study was high (90%, 584/650). Women who reported a prior surgical diagnosis of endometriosis had a greater risk of having a prior formal diagnosis of RLS (OR 4.82, 95% CI 1.66,14.02) and suffering RLS symptoms (OR 2.13, 95% CI 1.34–3.39) compared with those without a diagnosis. Women with either a formal diagnosis or symptoms associated with endometriosis have a significantly increased risk of having either a formal diagnosis or symptoms suggestive of RLS (OR 2.49, 95% CI 1.30, 3.64). In women suffering with endometriosis-associated symptoms, the cumulative endometriosis-associated symptom scores demonstrated a modest positive correlation with RLS severity scores (r = 0.42 95% CI 0.25 to 0.57). Limitations, reasons for caution The anonymous, voluntary self-completed questionnaire findings were not confirmed directly using medical records. However, our questionnaire that was piloted for acceptability prior to the study, allowed collation of information directly from women, regarding their clinically relevant symptoms that are important in diagnosing RLS. Wider implications of the findings: This is the first study highlighting an association between the symptoms relevant to these two chronic conditions, which may help in facilitating the discovery of novel therapeutic targets relevant to both. The simultaneous treatment of these conditions could potentially lead to improvement in overall quality of life for these women. Trial registration number NA

Can Endometriosis-Related Oxidative Stress Pave the Way for New Treatment Targets?

Endometriosis is a disease of reproductive age characterized by chronic pelvic pain and infertility. Its pathogenesis is complex and still partially unexplained. However, there is increasing evidence of the role of chronic inflammation, immune system dysregulation, and oxidative stress in its development and progression. The latter appears to be involved in multiple aspects of the disease. Indeed, disease progression sustained by a hyperproliferative phenotype can be related to reactive oxygen species (ROS) imbalance, as numerous experiments using drugs to counteract hyperproliferation have shown in recent years. Chronic pelvic pain is also associated with cell function dysregulation favoring chronic inflammation and oxidative stress, specifically involving macrophages and mast cell activation. Moreover, there is increasing evidence of a role for ROS and impaired mitochondrial function not only as deleterious effectors of the ovarian reserve in patients with endometriomas but also in terms of oocyte quality and, hence, embryo development impairment. Targeting oxidative stress looks to be a promising strategy to both curb endometriotic lesion progression and alleviate endometriosis-associated symptoms of chronic pain and infertility. More investigations are nevertheless needed to develop effective therapeutic strategies for clinical application.

Pain syndrome in adenomyosis. Finding new pathogenesis links and non-hormonal correction opportunities. Literature review

Adenomyosis is characterized by polymorphism of clinical manifestations and is the cause of chronic pelvic pain associated with endometriosis in 53–80% of cases. Heavy dysmenorrhea in adenomyosis is a key factor that reduces the quality of life and, moreover chronic pain reduces stress resistance and launches the rehabilitation cytokines cascade, which causes exacerbation of endometriosis. Formation of painful syndrome with adenomyosis may be due to: changes in neurohumoral regulation, stimulation of nerves and blood vessels growth and myometrium inflammatory remodeling against the background of circulatory disorders and vascular sclerosis. These processes lead to violation of neuroimmune relationships that determine the increase in the number and sensitivity of nociceptors against the background of the chronic immuno-inflammatory process in endometrials and myometry.Experimental studies have shown that the supraspinal role of the nitric oxide (NO) is to indirect mechanical nociceptive reflexes. The dose-dependent L-arginine role in the pain syndrome formation also was shown; it was found that small doses of L-arginine lead to the activation of nNO-synthase and analgesic effect. Large doses are activated by cotorphine synthase to form a dipeptide of cortorphine (L-tyrosine-L-arginine), which induces the met-enkephalin release and analgesic effect. Individual studies have demonstrated a decrease in the symptoms of urinary pain syndrome during L-arginine treatment, which made it possible to include it into the European Association of Urologists recommendations on the chronic pelvic pain treatment in 2017.Clinical comparative study (2013) of the NO donator (L-arginine) effectiveness in the treatment of endometriosis-associated intermenstrual pelvic pain and dysmenorrhea showed a high efficiency of a 3-month course of combination therapy (dienogest 2 mg + Tivortin 4.2 g). Supplement of basic therapy by NO donator (L-аrginine) has shown a faster reaching the clinical effect on reducing endometriosis-associated symptoms and sustainable maintenance of the result achieved. The multifaceted pharmacological effects of L-arginine directly affect a number of essential factors for the adenomyosis development and progression, which allows using this drug in clinical practice.

Role of surgical treatment in endometriosis.

Endometriosis can take one of three forms depending on its clinical presentation and management: endometriotic ovarian cyst (ovarian endometrioma), superficial or peritoneal endometriosis and deep infiltrating endometriosis (DIE).1Among them, DIE is considered the most aggressive, and the patient is often affected by more than one type together. The therapeutic methodology should not be influenced by a combination of different types of endometriotic lesion. According to the clinical context and the patient's needs, the treatment of this pathology can be medical or surgical. Although medical therapy could improve endometriosis-associated symptoms, it never offers a definite treatment for symptomatic patients, who often require surgical treatment. The rationale behind endometriosis surgical treatment is to achieve the complete removal of all lesions through a one-step surgical procedure; to obtain promising long-term results for pelvic pain, recurrence rate, and fertility; and to protect the functionality of the involved organs. Achieving these results depends on the total removal of the pathology from the pelvis, in an attempt to preserve, as much as possible, the healthy tissues surrounding the site of the disease. The choice of a surgical approach rather than medical therapy is subject to the patient's expectations, such as pregnancy desire, the effectiveness of treatment compared to possible complications, the type of pain and its intensity, and the location and severity of the disease. In this context, surgical management using a multidisciplinary endometriosis team is an important factor for achieving good outcomes.

Microbiome &amp; Endometriosis

Endometriosis is a chronic disease of the female reproductive system, which is characterised by the presence of endometrial tissue outside the uterus especially in the pelvic cavity that includes ovaries, fallopian tubes and it may occur extra genitally in some rare cases. 176 million women all over the world including 26 million in India suffer from endometriosis and high frequency was observed between the age group of 26-30 years, resulting in increased primary infertility. Various studies surveying the female reproductive tract have confirmed the existence of microbiota starting in the vagina, cervix, uterus, fallopian tubes and ovaries. These microbes play a crucial role at different stages ofthe reproduction, in forming a physical barrier against pathogen and the stimulation of host defence mechanisms. Direct and indirect mechanisms are observed including the production of biochemically active compounds that directly kill or inhibit pathogens. Women suffering from endometriosis lead an impaired quality of life and continue to deal with endometriosis-associated symptoms even after diagnosis and treatment of the disease. In endometriosis condition, adhesions are observed in the fallopian tubes and ovaries that block tubal motility and damage the oocyte-pickup. Progesterone resistance is familiar in endometriosis which changes the implantation window period causing the loss of implantation markers and finally leading to infertility. Malignant tumours of ovaries have also been identified and known to arise from endometriosis. Microbiome can be used as a novel diagnostic tool for endometriosis as there is a variation observed in the composition and distribution along the female reproductive tract of healthy women and endometriosis patients. A non-invasive diagnosis is achieved through this, aiming at early diagnosis and alternative treatment for endometriosis.

Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study.

BackgroundEndometriosis and restless leg syndrome (RLS) are both chronic conditions that can negatively affect a woman’s quality of life. A higher prevalence of RLS is seen in women and particularly in those who are pregnant, suggesting a possible ovarian hormonal influence. Endometriosis is a common (affecting 1 in 10 women) estrogen driven gynecological condition, and the prevalence of RLS in women with symptoms or a diagnosis of endometriosis is unknown.MethodsA prospective, cross-sectional, observational self-completed questionnaire study was distributed to 650 pre-menopausal women attending the gynecological department at Liverpool Women`s Hospital over a period of 4 months. 584 questionnaires were returned and 465 completed questionnaires were included in the final dataset. Data on RLS-associated (The International Restless Leg Syndrome Study Group rating scale) and endometriosis-associated (modified-British Society of Gynaecological Endoscopists pelvic pain questionnaire) symptoms were collected.ResultsWomen who reported a prior surgical diagnosis of endometriosis had a greater risk of having a prior formal diagnosis of RLS (OR 4.82, 95% CI 1.66,14.02) and suffering RLS symptoms (OR 2.13, 95% CI 1.34-3.39) compared with those without a diagnosis. When women with either a formal surgical diagnosis or symptoms associated with endometriosis were grouped together, they also have a significantly increased risk of having either a formal diagnosis or symptoms suggestive of RLS (OR 2.49, 95% CI 1.30, 3.64). In women suffering with endometriosis-associated symptoms, the cumulative endometriosis-associated symptom scores demonstrated a modest positive correlation with RLS severity scores (r=0.42 95% CI 0.25 to 0.57).ConclusionsThis is the first study highlighting an association between the symptoms relevant to the two chronic conditions RLS and endometriosis, showing that women with a reported prior surgical diagnosis or symptoms suggestive of endometriosis have a significantly higher prevalence of a prior formal diagnosis or symptoms suggestive of RLS. This data will help in facilitating the discovery of novel therapeutic targets relevant to both conditions. The simultaneous treatment of these conditions could potentially lead to improvement in the overall quality of life for these women.

Somatic Genomic Events in Endometriosis: Review of the Literature and Approach to Phenotyping.

In this review, we provide a survey and appraisal of research into somatic genomic events in endometriosis. Methodologies have evolved from conventional cytogenetics to next-generation sequencing, with findings ranging from chromosome imbalances to recurrent somatic cancer driver mutations. Somatic cancer driver mutations have been described in a range of endometriosis lesions, dominated by recurrent mutations in KRAS and PIK3CA as well as loss of PTEN and BAF250a (ARID1A). These somatic events appear to be largely restricted to the endometriosis glandular epithelium. Somatic mutations, particularly PTEN loss, have also been observed in eutopic (uterine) endometrium, although at lower mutant allele frequencies compared with ectopic lesions. Systematic studies of the potential clinical phenotype of these somatic genomic events have yet to be performed. Thus, we propose a framework to investigate the potential clinical phenotype associated with somatic genomic events in endometriosis. Technical requirements include pathology review of histological endometriosis, microdissection for tissue enrichment, orthogonal validation of whole genome/exome sequencing, and a germline sample for confirmation of somatic origin. Clinical requirements include annotation of surgical findings; patient demographics; cross-sectional and prospective data on pain and fertility; consideration of sampling multiple lesions in each patient, mutant allele frequency, and somatic events in the eutopic endometrium; and confirmation of any associations with mechanistic studies. Given the multifactorial nature of endometriosis-associated symptoms, it is likely that somatic events have small (or at most, moderate) effect sizes, and thus careful consideration will have to be given to future study design.

Towards an understanding of the molecular mechanisms of endometriosis-associated symptoms (Review)

Towards an understanding of the molecular mechanisms of endometriosis-associated symptoms (Review)

The effects of nutrients on symptoms in women with endometriosis: a systematic review.

The success rate of medical and surgical treatment for endometriosis is limited. Empowering patients suffering from endometriosis by giving them opportunities to positively influence their symptoms could result in increased quality of life. Changing diet is one of these self-management activities, but current endometriosis diets are mostly based on limited evidence. In order to gain more insight into the role of nutrients on symptoms in women with endometriosis a systematic review was carried out in which the effect of a nutrient or diet on endometriosis-related symptoms was investigated. PubMed and the Cochrane Database of Systematic Reviews were searched for relevant articles up to 1 March 2019. Search terms included endometriosis, diet, and 26 possible nutrients were identified after assessing available endometriosis diets in the literature and on the internet. Twelve studies were included. Study quality, including risk of bias, was assessed using GRADE criteria and all were of low to very low quality. Intake of additional fatty acids, antioxidants and a combination of vitamins and minerals may have a positive effect on endometriosis-associated symptoms. Future studies are necessary to gain evidence about which food products are effective and in which amounts.