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Introduction: Prior studies have investigated the diagnostic potential of microRNA (miRNA) expression profiles for endometriosis. However, the vast majority of previous studies have only included adult women. Therefore, we sought to investigate differential expression of miRNAs among adolescents and young adults with endometriosis., Methods: The Women's Health Study: from Adolescence to Adulthood (A2A) is an ongoing WERF EPHect compliant longitudinal cohort. Our analysis included 64 patients with surgically-confirmed endometriosis (96% rASRM stage I/II) and 118 females never diagnosed with endometriosis frequency matched on age (median = 21 years) and hormone use at blood draw. MicroRNA measurement was separated into discovery (10 cases and 10 controls) and internal replication (54 cases and 108 controls) phases. The levels of 754 plasma miRNAs were assayed in the discovery phase using PCR with rigorous internal control measures, with the relative expression of miRNA among cases vs. controls calculated using the 2 -ΔΔCt method. miRNAs that were significant in univariate analyses stratified by hormone use were included in the internal replication phase. The internal replication phase was split 2:1 into a training and testing set and utilized FirePlex miRNA assay to assess 63 miRNAs in neural network analyses. The testing set of the validation phase was utilized to calculate the area under the curve (AUC) of the best fit models from the training set including hormone use as a covariate., Results: In the discovery phase, 49 miRNAs were differentially expressed between endometriosis cases and controls. The associations of the 49 miRNAs differed by hormone use at the time of blood draw. Neural network analysis in the testing set of the internal replication phase determined a final model comprising 5 miRNAs (miR-542-3p, let-7b-3p, miR-548i, miR-769-5p, miR-30c-1-3p), yielding AUC = 0.77 (95% CI: 0.67-0.87, p  < 0.001). Sensitivity in the testing dataset improved (83.3% vs. 72.2%) while the specificity decreased (58.3% vs. 72.2%) compared to the training set., Conclusion: The results suggest that miR-542-3p, let-7b-3p, miR-548i, miR-769-5p, miR-30c-1-3p may be dysregulated among adolescent and young adults with endometriosis. Hormone use was a significant modifier of miRNA dysregulation and should be considered rigorously in miRNA diagnostic studies., Competing Interests: KT, NS and KE receive grant funding from Aspira Women's Health, which is not related to this study. MH is a medical advisory board member for WIN Fertility, Intelon Optics, and contributing author for UpToDate. SM receives research support from National Institutes of Health, Department of Defense, AbbVie, and Marriot Family Foundations. She is Field Chief Editor for Frontiers in Reproductive Health and has served on advisory boards for AbbVie, Abbot, and Organon. AS is involved in a systematic review with Bayer Pharmaceuticals about endometriosis-associated pain and quality of life, which is unrelated to the this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Brady, Yousif, Sasamoto, Vitonis, Fendler, Stawiski, Hornstein, Terry, Elias, Missmer and Shafrir.)

Introduction: 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., Methods: 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., Results: 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)., Discussion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mongiovi, Wallace, Goodwin, Vitonis, Karevicius, Shafrir, Sasamoto, DiVasta, Sieberg, Terry and Missmer.)

Background: Peritoneal fluid is a medium for endometriosis-associated biomarker discovery from which the local peritoneal environment and pathophysiologic pathways are often inferred. Therefore, we evaluated the associations between peritoneal fluid color and volume at time of endometriosis-related laparoscopic surgery with patient characteristics, endometriosis type and lesion location in adolescents and young adults with endometriosis., Methods: We conducted a cross-sectional analysis among 545 patients undergoing surgery for endometriosis who enrolled in the Women's Health Study: from Adolescence to Adulthood cohort study. Patient characteristics, surgically visualized endometriosis phenotypes, and gross characteristics of peritoneal fluid were collected in compliance with World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. Chi-square or Fisher's exact tests were applied to test for differences across categories., Results: Most of the patients were adolescents or young adults (86% age <25 years) of white race (89%), with only superficial peritoneal lesions and rASRM stage = I/II observed at surgery (both 95%). We observed variation in peritoneal fluid color across different menstrual cycle phases at time of surgery ( p  = 0.006). Among those who were cycling at time of surgery, endometriosis patients with red peritoneal fluid were most likely to be in the proliferative phase (49%) compared to the secretory phase (27%), while those with yellow or orange peritoneal fluid were most likely to be in the secretory phase (57% and 86% respectively). Yellow color was significantly less common in those taking combined oral contraceptives but much more common with progesterone only formulation exposure ( p  = 0.002). Peritoneal fluid volume did not differ by cycle phase but was more likely to be low (≤6 ml) for those exposed to hormones at time of surgery ( p  = 0.01). Those with acyclic pelvic pain were less likely to have red peritoneal fluid ( p  = 0.001) but had greater volume ( p  = 0.02) compared to those without., Conclusion: Our findings highlight the importance of accounting for menstrual cycle phase and hormonal exposures when designing research using peritoneal fluid samples and inferring from biomarker results intended to advance our understanding of endometriosis and associated symptom pathophysiology., Competing Interests: KT and NS receive grant funding from Aspira Women's Health, which is not related to this study. SM reports consultancy for and grant funding from AbbVie for population-based research unrelated to this project and from Frontiers in Reproductive Health as Field Chief Editor. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yousif, DePari, Vitonis, Harris, Shafrir, Terry, Missmer and Sasamoto.)