Endometriosis-associated Pain Research Articles

Optimizing Hormone Treatment Choices in Patients with Endometriosis-Associated Chronic Pelvic Pain: A Tertiary Centre Perspective

Optimizing Hormone Treatment Choices in Patients with Endometriosis-Associated Chronic Pelvic Pain: A Tertiary Centre Perspective

Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3).

Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3).

Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability

Background Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients’ quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment. Objective To evaluate DNG as a long-term treatment of endometriosis, focusing on patients’ compliance and side effects, also correlating with different phenotypes of endometriosis. Methods This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items. Results At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability. Conclusions DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

Relugolix/Estradiol/Norethisterone Acetate: A Review in Endometriosis-Associated Pain.

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate [Myfembree® (USA); Ryeqo® (EU)] (hereafter referred to as relugolix combination therapy) has been approved in the USA for the management of moderate to severe pain associated with endometriosis in premenopausal women and in the EU for the symptomatic treatment of endometriosis in adult women of reproductive age with a history of previous medical or surgical treatment for their endometriosis. The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix decreases estradiol and progesterone levels, while the addition of estradiol/norethisterone acetate mitigates hypoestrogenic effects including bone mineral density (BMD) loss and vasomotor symptoms. In two pivotal phaseIII trials, relugolix combination therapy significantly improved dysmenorrhoea and non-menstrual pelvic pain in premenopausal women with moderate to severe endometriosis. The combination also reduced overall pelvic pain and dyspareunia, reduced analgesic and opioid use, and improved health-related quality of life. The efficacy of relugolix combination therapy was sustained over the longer term (up to 2years). Relugolix combination therapy was generally well tolerated and BMD loss over time was minimal. With the convenience of a once daily oral dosing regimen, relugolix combination therapy is a valuable addition to the options currently available for the management of endometriosis-associated pain.

Superficial Peritoneal Endometriosis Vaporization Using a CO2 Laser: A Long-Term Single-Center Experience.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometriosis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with superficial peritoneal endometriosis (SPE) who underwent laparoscopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirmation of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among patients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were observed postoperatively (p-value < 0.01), indicating enhanced quality of life. Among infertile patients with an active desire for pregnancy, surgical treatment showed an overall pregnancy rate after surgery of 93.7% (p-value < 0.01), including 75.7% natural pregnancies and 24.3% IVF. Laser vaporization enabled precise lesion removal with minimal tissue damage, short operative time, and minimal blood loss. Conclusions: Laparoscopic laser vaporization is an effective treatment for SPE, offering pain relief, improved quality of life, and favorable fertility outcomes. Further research is needed to validate these results in terms of pain control and fertility.

Vilaprisan for the treatment of symptomatic endometriosis: results from a terminated phase 2b randomized controlled trial

ObjectiveEvaluate efficacy and safety of two doses of vilaprisan versus placebo in participants with symptomatic endometriosis. DesignMulticenter, randomized, double-blind, placebo-controlled, parallel-group phase 2b trial (NCT03573336). The initially planned sample size was 315 patients. Recruitment was paused to assess long-term toxicity findings in rodents; although findings were assessed as likely to be of limited clinical relevance in humans, the study was closed by the sponsor. During the pause, enrolled patients completed 3 or 6 months of treatment per their assigned regimen. ParticipantsPre-menopausal adults with confirmed endometriosis and moderate-to-severe pelvic pain (≥4/10 on a numerical rating scale) were enrolled. Inclusion required protocol adherence, including ≥24 diary entries, and an average pain score of ≥3.5. InterventionParticipants were randomly assigned 1:1:1 to receive vilaprisan 2 mg, vilaprisan 4 mg, or placebo. Main Outcome MeasuresPrimary outcome was change in 7-day mean “worst pain” (per the Endometriosis Symptom Diary item 1) from baseline to Month 3. All analyses were descriptive only. ResultsEight participants were randomly assigned to treatment before the study pause: six received vilaprisan (4 mg, n=4; 2 mg, n=2) and two received placebo. The six vilaprisan recipients experienced an improvement in endometriosis-associated pelvic pain, whereas the two placebo recipients experienced no change or increased pain; all eight participants had decreased use of pain medication. Bleeding intensity decreased from baseline in the vilaprisan group. ConclusionThe study findings suggest that vilaprisan may improve outcomes in patients with endometriosis. Further studies in larger populations would be needed to accurately assess treatment effects.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: V. Physical examination standards in endometriosis research

The World Endometriosis Research Foundation established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, 4 data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards underwent multiple rounds of iterations and revisions. N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of back and pelvic girdle; abdomen including allodynia and trigger points; vulva including provoked vestibulodynia; pelvic floor muscle tone and tenderness; tenderness on unidigital pelvic examination; presence of pelvic nodularity; uterine size and mobility; presence of adnexal masses; presence of incisional masses; speculum examination; tenderness and allodynia at an extra-pelvic site (e.g., forearm); and recording of anthropometrics. The EPHect-PE standards will facilitate the standardized documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.

Plasma proteins and persistent post-surgical pelvic pain among adolescents and young adults with endometriosis

Non-invasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biological pathways underlying endometriosis-associated pain and symptom progression. Thus, we evaluated plasma proteins in relation to persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. We conducted a prospective analysis including 142 participants with laparoscopically- confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood (A2A) observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1,305 plasma protein levels including markers for immunity, angiogenesis and inflammation using SomaScan. Worsening or persistent post-surgical pelvic pain was defined as having newly developed, persistent (i.e., stable), or worsening severity, frequency, or persistent life-interference of dysmenorrhea or acyclic pelvic pain at one-year post-surgery compared to pre-surgery. We calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression adjusted for age, body mass index, and fasting status and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. Median age at blood draw was 17 years (interquartile range 15-19), and most participants were white race (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year post-surgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, while pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain one-year post-surgery (nominal p<0.05). Compared to those with improved pelvic pain one year post-surgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (OR=2.98, 95% CI:1.44-6.19) and CD47 (OR=2.68, 95%CI=1.28-5.61), but lower levels of Sonic Hedgehog protein (SHH; OR=0.55, 95%CI=0.36-0.84) in pre-surgical blood. Pathways related to cell migration were upregulated and pathways related to angiogenesis were downregulated in those with worsening/persistent post-surgical pelvic pain compared to those with improved pain. When we examined change in proteins levels from pre- to post-surgery and its subsequent risk of worsening/persistent post-surgical pain at one-year follow-up, we observed increasing levels of SHH from pre- to post-surgery was associated with four-fold increase in risk of post-surgical pain (OR quartile 4 vs. 1=3.86, 1.04-14.33). Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain post-surgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

Quality of life and symptoms of pain in patients with endometriomas compared to those with other endometriosis lesions: a cross-sectional study

BackgroundEndometriomas are genetically distinct from other endometriosis lesions and could be associated with a predisposition to excessive inflammation. However, differences in clinical presentation between types of endometriosis lesions have not been fully elucidated. This study aimed to investigate the quality of life and pain scores of patients with endometriomas compared to those with other types of endometriosis lesions.MethodsA cross-sectional observational study was conducted between January 2020 and August 2023. Patients diagnosed with endometriosis completed the Endometriosis Health Profile 30 pain subscale questionnaire for their quality of life score and rated their endometriosis-associated pain symptoms using an 11-point numerical rating scale. The data were analyzed for comparison through multivariate linear regression models.ResultsA total of 248 patients were included and divided into endometrioma (81, 33%) and nonendometrioma (167, 67%) groups. The mean age of the patients was 37.1 ± 7.5 years. Most participants were Canadian or North American (84%). One-third of the patients reported experiencing up to four concurrent pain symptoms. The most reported pain included deep dyspareunia (90%), chronic pelvic pain (84%) and lower back pain (81%). The mean quality of life score was 45.9 ± 25.9. We observed no difference in quality of life scores between patients with and without endometriomas. Patients with endometriomas had lower mean scores for deep dyspareunia (0.8; 95% CI [0 to 1.5]; p = 0.049) and higher mean scores for superficial dyspareunia (1.4; 95% CI [0.2 to 2.6]; p = 0.028). Comorbid infertility (p = 0.049) was a factor that modified superficial dyspareunia intensity in patients with endometriomas.ConclusionIn patients with endometriosis, evidence was insufficient to conclude that the presence of endometriomas was not associated with a greater or lesser quality of life, but differences in specific symptoms of dyspareunia were identified.

Differences in characteristics and use of complementary and alternative methods for coping with endometriosis-associated acyclic pelvic pain across adolescence and adulthood.

Over four million women in the US alone have been diagnosed with endometriosis. For those living with this disease, surgery and hormonal treatment reduce associated pelvic pain in some, while others continue to experience life impacting pain. Therefore, identification of accessible and cost-effective methods of pain reduction to compliment current treatment is urgently needed. Our objective was to quantify the prevalence of complementary and alternative methods used to manage acyclic pelvic pain and their reported benefit among women of different age groups living with endometriosis. We used baseline questionnaire data from laparoscopically-confirmed endometriosis cases who completed a WERF EPHect compliant questionnaire in the longitudinal cohort of The Women's Health Study: From Adolescence to Adulthood (A2A). Participants with acyclic pelvic pain were asked to indicate specific methods or activities that either helped or worsened their pelvic/lower abdominal pain. Differences among age groups [adolescent (<18 years), young adult (18-25 years), and adult (>25 years)] were assessed using Fisher's exact test. Of the 357 participants included in analysis, sleep for coping was reported more frequently among adolescents (n = 59, 57.3%) compared to young adults (n = 40, 44.0%) and adults (n = 19, 31.1%; p = 0.004). Adolescents also reported more frequent use of music (n = 29, 21.2%) than young adults (n = 10, 7.0%) and adults (n = 7, 9.1%; p = 0.001). Exercise worsened pain most commonly among adolescents (n = 82, 59.9%), followed by younger adults (n = 67, 46.9%), and adults (n = 27, 35.1%; p = 0.002). Our analysis of participants in the A2A cohort showed that the prevalence of complementary and alternative methods used for coping with endometriosis-associated acyclic pelvic pain varied by age group. Future studies should aim to provide information that will further inform decisions in making care plans for managing endometriosis-associated pain that is effective, accessible, and tailored to the preferences of the patient.

Mental Health Outcomes of Endometriosis Patients during the COVID-19 Pandemic: Impact of Pre-pandemic Central Nervous System Sensitization

To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0–100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. PerspectiveThis article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors.

Evaluation of Efficacy and Safety of 2 mg vs 4 mg Dienogest in Endometriosis: A Randomised Single-blind Dose-ranging Trial

Introduction: Endometriosis is a recurring chronic inflammatory condition that affects females of reproductive age. Endometriosis-associated Pelvic Pain (EAPP) adversely impacts physical, mental, and social well-being. Currently, there is no ideal treatment option. Dienogest, a selective progestin, shows a pronounced effect on endometriosis. Aim: To compare the efficacy and safety of Dienogest at doses of 2 mg and 4 mg/day orally in the treatment of endometriosis. Materials and Methods: An observer-blind, parallel-group, randomised clinical trial was conducted in the Department of Obstetrics and Gynaecology at IPGME&amp;R, SSKM Hospital, Kolkata, West Bengal, India, from April 2016 to December 2017. A total of 190 women aged 20-45 years suffering from endometriosis were recruited and divided into two treatment groups, A and B, receiving daily doses of 2 mg and 4 mg, respectively, for 24 weeks. Relief of EAPP was assessed using the Visual Analogue Scale (VAS) score, and improvement in Quality of Life (QoL) was measured. Treatment-related adverse events were also recorded. Numerical variables were compared using Student’s t-test or the Mann-Whitney U Test, and categorical variables were compared using the Chi-square test or Fisher’sexact test. Results: The absolute reduction in pelvic pain VAS score was 39.71±8.60 at 24 weeks from the initial score of 70.88 (Mean VAS score before treatment with Dienogest) in Group A, compared to 34.80±6.45 from 69.34 (Mean VAS score before treatment with Dienogest) in Group B (p=0.0001). The difference in mean VAS at 24 weeks between the two groups was statistically significant (p=0.0002). At 24 weeks, 18 (24.66%) patients in Group A experienced an irregular bleeding pattern compared to 27 (40.30%) in Group B, with spotting being the most common issue. Adverse effects such as weight gain, acne, alopecia, depression, and decreased libido were observed in both groups, but they were more pronounced in the 4 mg group. Conclusion: The efficacy and safety results from this doseranging study of Dienogest indicate that 2 mg/day is the effective dose for treating endometriosis and offers better tolerability compared to the 4 mg dose.

Resolution of the First Ukrainian endometriosis forum “Drug treatment for endometriosis-associated pelvic pain. The quality of a woman’s life”

Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis.The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.

Gut Microbiota and Endometriosis: Exploring the Relationship and Therapeutic Implications.

Endometriosis is a common inflammatory disease affecting women of reproductive age, characterized by the growth of endometrial tissue beyond the uterus. In addition to gynecological manifestations, many endometriosis patients experience gastrointestinal symptoms, indicating a potential association between gut health and the disease. Recent studies have revealed alterations in the gut microbiota of individuals with endometriosis, including reduced diversity, microbial composition imbalances, and pathogenic bacteria. These changes can disrupt immune function, increase inflammation, and contribute to the chronic inflammatory state observed in endometriosis. Moreover, dysregulation of intestinal permeability may further exacerbate gastrointestinal symptoms in affected individuals. Understanding the role of the gut microbiota and intestinal permeability in endometriosis can provide valuable insights into disease pathogenesis, aid in non-invasive diagnostic approaches, and open new avenues for therapeutic interventions. Probiotics, in particular, have shown promise in improving endometriosis-associated pain symptoms and reducing endometriotic lesions in animal models. This review suggests that additional research and well-designed clinical trials are necessary to validate the potential diagnostic and therapeutic benefits of manipulating the gut microbiota in managing endometriosis and its gastrointestinal symptoms, thereby improving the quality of life for those affected.

#75 : Mechanisms and Active Ingredients of Chinese Herbal Medicine on Ameliorating Endometriosis-Associated Pain

Background and Aims: Chinese herbal medicines (CHMs) have been effectively used to treat the endometriosis-associated pain (EAP), but its pharmacological and molecular mechanism remains unclear. In this study, we aim to use a network pharmacology-based approach to identify the potential therapeutic targets and active ingredients of CHM for EAP, and to verify their pharmaceutical actions on an experimental mouse model. Method: Pharmacological networks of 3 common CHM formulae for endometriosis (HXXYF, SFZYT and GXZYT) were built by targets collated from public databases, and the enrichment molecular pathway analysis was applied to select the potential pharmacological targets and CHM active ingredients. Pain assessments on the experimental mouse model were performed to evaluate efficacy of the CHM formulae and potential active ingredients. RT-PCR and immunostaining in endometriotic lesions were used to confirm the expression of the potential targets after treatment. Results: ‘Inflammatory mediator regulation of TRP channels’ was a major molecular pathway with highest significance in pharmacological network and enrichment analysis. In mouse, 2 CHM formulae, HXXYF and SFZYT, significantly reduced pain responses, while pain-related inflammatory mediators, IL1[Formula: see text] and PGE2, were significantly decreased after treatment. Meanwhile, densities of nerve fibers in lesions were significantly lower as well, with significantly lower expressions of TRPA1 and TRPV1. 3 CHM ingredients (baicalein, paeoniflorin and quercetin) with highest degree in pharmacological network were then selected for in-depth investigation. However, only paeoniflorin significantly reduced stimuli-evoked and non-stimuli-evoked pain in mice, along with effective reduction in all above parameters. Conclusion: Our study demonstrated multi-targets effects of CHM on EAP relief through inflammatory and neuropathic pathways, which supports CHM as alternative or complementary therapy for EAP. The active ingredients from CHM may provide a novel drug development and approach for EAP treatment.

Expression of Concern: “Laparoscopic Excision Versus Ablation for Endometriosis-Associated Pain: An Updated Systematic Review and Meta-analysis”

Expression of Concern: “Laparoscopic Excision Versus Ablation for Endometriosis-Associated Pain: An Updated Systematic Review and Meta-analysis”

10332 Association of Norethindrone Treatment Duration and Patient Characteristics with Improvement of Endometriosis-Associated Pain

10332 Association of Norethindrone Treatment Duration and Patient Characteristics with Improvement of Endometriosis-Associated Pain

10173 Long-Term Therapy of Elagolix + Add-Back Therapy in Women with Endometriosis-Associated Pain for 48 Months: Update on Bone Mineral Density

10173 Long-Term Therapy of Elagolix + Add-Back Therapy in Women with Endometriosis-Associated Pain for 48 Months: Update on Bone Mineral Density

Dienogest in endometriosis treatment: A narrative literature review.

Endometriosis is characterized by the implantation of endometrial cells outside the uterus. This hormone-dependent disease is highly prevalent among women of reproductive age. Clinical symptoms of endometriosis include dysmenorrhea, pelvic pain, and infertility, which can negatively impact the overall quality of life of those affected. The medical treatment of endometriosis serves as an important therapeutic option, aimed at alleviating pain associated with the condition and suppressing the growth of endometriotic lesions. As such, it is employed as an adjuvant therapy following surgery or an empirical treatment after the clinical diagnosis of endometriosis. Dienogest, a fourth-generation progestin, has received approval for the treatment of endometriosis in many countries. A growing body of evidence has demonstrated its efficacy in managing endometriosis-associated pain, preventing symptoms, and reducing lesion recurrence. In this review, we examine the clinical efficacy, safety, and tolerability of dienogest in treating endometriosis. We also provide updated findings, drawing from clinical studies that focus on the long-term use of this medication in patients with endometriosis.

Update on the management of endometriosis-associated pain in France

The French National College of Obstetricians and Gynecologists (CNGOF) published guidelines for managing endometriosis-associated pain in 2018. Given the development of new pharmacological therapies and a review that was published in 2021, most national and international guidelines now suggest a new therapeutic approach.In addition, a novel validated screening method based on patient questionnaires and analysis of 109-miRNA saliva signatures, which combines biomarkers and artificial intelligence, opens up new avenues for overcoming diagnostic challenges in patients with pelvic pain and for avoiding laparoscopic surgery when sonography and MRI are not conclusive.Dienogest (DNG) 2 mg has been a reimbursable healthcare expense in France since 2020, and, according to recent studies, it is at least as effective as combined hormonal contraception (CHC) and can be used as an alternative to CHC for first-line treatment of endometriosis-associated pain. Since 2018, the literature concerning the use of DNG has grown considerably, and the French guidelines should be modified accordingly.The levonorgestrel intrauterine system (LNG IUS) and other available progestins per os, including DNG, or the subcutaneous implant, can be offered as first-line therapy, gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (ABT) as second-line therapy.Oral GnRH antagonists are promising new medical treatments for women with endometriosis-associated pain. They competitively bind to GnRH receptors in the anterior pituitary, preventing native GnRH from binding to GnRH receptors and from stimulating the secretion of luteinizing hormone and follicle-stimulating hormone. Consequently, estradiol and progesterone production is reduced. Oral GnRH antagonists will soon be on the market in France. Given their mode of action, their efficacy is comparable to that of GnRH agonists, with the advantage of oral administration and rapid action with no flare-up effect. Combination therapy with ABT is likely to allow long-term treatment with minimal impact on bone mass. GnRH antagonists with ABT may thus be offered as second-line treatment as an alternative to GnRH agonists with ABT.This article presents an update on the management of endometriosis-associated pain in women who do not have an immediate desire for pregnancy.