Effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Endometriosis Symptoms Management and Quality of Life: An International Survey Study

Effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Endometriosis Symptoms Management and Quality of Life: An International Survey Study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 24 February 2026 V1 Latest version Share on Effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Endometriosis Symptoms Management and Quality of Life: An International Survey Study Authors : Mahsa Gholiof 0009-0003-6732-857X [email protected] , Narges Kalani , and Mathew Leonardi Authors Info & Affiliations https://doi.org/10.22541/au.177194722.27223197/v1 2313 views 546 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objective To characterize patterns of glucagon-like peptide-1 receptor agonist (GLP-1RA) use and their perceived effects on endometriosis-related symptoms, quality of life, treatment burden, and symptom recurrence following discontinuation. Design International, anonymous, cross-sectional survey study. Setting Online survey distributed through endometriosis advocacy platforms, social media, and clinical networks. Population or Sample Individuals aged 18–55 years, assigned female at birth, with confirmed or suspected endometriosis and current or prior GLP-1RA use. Methods Participants completed a structured questionnaire capturing demographic and clinical characteristics, GLP-1RA type and duration, side effects, and perceived symptom changes using a 7-point Global Rating of Change scale (−3 = significant worsening to +3 = significant improvement). Within-subject changes in symptoms, body weight, and treatment utilization were analyzed using paired and one-sample t tests. Associations between percentage weight change and symptom improvement were explored using Spearman correlation. Open-ended responses were analyzed using structured content analysis. Main Outcome Measures Self-reported changes in endometriosis-related pain, gastrointestinal and menstrual symptoms, quality of life, treatment burden, and symptom recurrence after discontinuation. Results Of 186 respondents, 161 met inclusion criteria (mean age 35.8 ± 6.8 years). Most used semaglutide (75.2%) or tirzepatide (19.9%). Significant weight reduction was observed (mean difference 12.07 kg; p < 0.001). Overall, 64.6% reported improvement in at least one endometriosis-related symptom, and 33.7% reported complete resolution of at least one symptom. Significant improvements were observed in pelvic pain, bloating, lower back pain, and multiple quality-of-life domains (all p < 0.001). Greater weight loss correlated with greater improvement in overall quality of life (ρ = 0.443, p < 0.001). Medication and alternative therapy use decreased significantly (both p < 0.001). Among those who discontinued therapy, 60.3% reported symptom recurrence. Conclusions GLP-1RA use was associated with self-reported improvements in symptom burden and quality of life, with recurrence after discontinuation suggesting sustained benefit may require ongoing therapy. Prospective studies are warranted to evaluate GLP-1RAs as adjunctive treatments in endometriosis. Effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Endometriosis Symptoms Management and Quality of Life: An International Survey Study Authors: Mahsa Gholiof 1 , Narges Kalani 1 , Mathew Leonardi 1 Affiliations: 1. Department of Obstetrics & Gynecology, McMaster University, Hamilton, Ontario, Canada Corresponding Author: Mahsa Gholiof (1200 Main Street West, 2F clinic, Hamilton, ON L8N 3Z5, [email protected] , (647)767-5606) Short Title: Patient-Reported Impact of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Endometriosis Symptoms and Quality of Life Objective To characterize patterns of glucagon-like peptide-1 receptor agonist (GLP-1RA) use and their perceived effects on endometriosis-related symptoms, quality of life, treatment burden, and symptom recurrence following discontinuation. Design International, anonymous, cross-sectional survey study. Setting Online survey distributed through endometriosis advocacy platforms, social media, and clinical networks. Population or Sample Individuals aged 18–55 years, assigned female at birth, with confirmed or suspected endometriosis and current or prior GLP-1RA use. Methods Participants completed a structured questionnaire capturing demographic and clinical characteristics, GLP-1RA type and duration, side effects, and perceived symptom changes using a 7-point Global Rating of Change scale (−3 = significant worsening to +3 = significant improvement). Within-subject changes in symptoms, body weight, and treatment utilization were analyzed using paired and one-sample t tests. Associations between percentage weight change and symptom improvement were explored using Spearman correlation. Open-ended responses were analyzed using structured content analysis. Main Outcome Measures Self-reported changes in endometriosis-related pain, gastrointestinal and menstrual symptoms, quality of life, treatment burden, and symptom recurrence after discontinuation. Results Of 186 respondents, 161 met inclusion criteria (mean age 35.8 ± 6.8 years). Most used semaglutide (75.2%) or tirzepatide (19.9%). Significant weight reduction was observed (mean difference 12.07 kg; p < 0.001). Overall, 64.6% reported improvement in at least one endometriosis-related symptom, and 33.7% reported complete resolution of at least one symptom. Significant improvements were observed in pelvic pain, bloating, lower back pain, and multiple quality-of-life domains (all p < 0.001). Greater weight loss correlated with greater improvement in overall quality of life (ρ = 0.443, p < 0.001). Medication and alternative therapy use decreased significantly (both p < 0.001). Among those who discontinued therapy, 60.3% reported symptom recurrence. Conclusions GLP-1RA use was associated with self-reported improvements in symptom burden and quality of life, with recurrence after discontinuation suggesting sustained benefit may require ongoing therapy. Prospective studies are warranted to evaluate GLP-1RAs as adjunctive treatments in endometriosis. Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The study was conducted without external financial support, and therefore no external peer review for scientific quality or priority assessment by a funding body was undertaken. The design, conduct, analysis, and reporting of this research were entirely the responsibility of the authors. Keywords Endometriosis; GLP-1 receptor agonists; Semaglutide; Tirzepatide; Pelvic pain; Bloating; Quality of life; Patient-reported outcomes; Discontinuation effects 1. Introduction Endometriosis is a chronic, estrogen-dependent inflammatory condition affecting approximately 10% of women and individuals assigned female at birth, characterized by endometrial-like tissue outside the uterus. Common symptoms include pelvic pain, dysmenorrhea, gastrointestinal symptoms, and infertility [1][2], contributing to reduced quality of life, substantial healthcare, and socioeconomic burdens [3]. Existing treatments, hormonal suppression, analgesics, and surgery are often partially effective and are limited by side effects and high recurrence rates [4][5]. This underscores a growing need for adjunctive therapies that address both pathophysiology and the diverse symptom burden of endometriosis. Emerging evidence links endometriosis to systemic metabolic dysfunction, chronic inflammation, and disrupted immune–endocrine signaling [6]. Obesity, insulin resistance, and altered adipokine profiles have been associated with heightened inflammation and pain severity [7][8], prompting interest in agents with dual metabolic and anti-inflammatory properties. GLP-1 receptor agonists (GLP-1RAs), including semaglutide, liraglutide, and tirzepatide are incretin-based therapies approved for type 2 diabetes and obesity [9]. Beyond weight loss, GLP-1RAs suppress pro-inflammatory cytokines (e.g., TNF-α, IL-6) [10][11], improve mitochondrial function [12], reduce oxidative stress [10][13], enhance insulin sensitivity, and modulate hypothalamic–pituitary–gonadal axis activity and adipokine signaling [14][15]. GLP-1RAs receptors are also expressed in tissues involved in pain processing, and animal studies suggest GLP-1RAs exert central anti-nociceptive effects through microglial modulation and neuro-immune pathways [16]. Given these mechanistic overlaps, GLP-1RAs represent a potential adjunctive therapy for endometriosis. However, no studies have evaluated their use in this population. This study aimed to characterize individuals with endometriosis who used GLP-1RAs, assess usage patterns and perceived effects on symptoms and quality of life, and explore outcomes following discontinuation. 2. Methods 2.1 Study Population and Survey Design Eligible participants were individuals aged 18–55, assigned female at birth, with a confirmed or suspected endometriosis diagnosis, and current or prior use of a GLP-1RA. The survey was hosted on the Research Electronic Data Capture (REDCap) platform and distributed via online endometriosis communities, social media, and clinical networks. The survey was designed to capture comprehensive, patient-reported information on endometriosis history, management strategies, and experiences with GLP-1RA therapy. It included the following domains: (1) demographic characteristics; (2) endometriosis diagnosis and symptom history; (3) current and past management methods; (4) GLP-1RA use (e.g., type, duration, side effects); (5) changes in endometriosis-related symptoms during GLP-1RA use; and (6) effects of discontinuing GLP-1RA therapy. Two open-ended questions were included at the end of the survey to explore patients’ experiences with GLP-1RAs use in the context of endometriosis (Appendix S1). Perceived symptom changes were assessed using a 7-point Global Rating of Change scale ranging from −3 (“significant worsening”) to +3 (“significant improvement”), with intermediate categories (−2 to +2) and 0 indicating “no change.” This bidirectional format captures both magnitude and direction of perceived change and is consistent with global change scales widely used in clinical and patient-reported outcomes research to assess subjective improvement or deterioration over time [17][18]. 2.2 Outcome Measures This study assessed the perceived effects of GLP-1RAs on endometriosis-associated symptoms, as well as participant characteristics and treatment experiences. The primary outcome was self-reported change in endometriosis symptoms during GLP-1RA use, measured across multiple domains: pelvic pain (menstrual and non-menstrual), lower back and leg/hip/thigh pain, gastrointestinal symptoms (bloating, bowel habit changes, rectal pain/bleeding, nausea/vomiting), genitourinary symptoms (urinary urgency/frequency, pain during urination), menstrual symptoms (heavy/prolonged bleeding, irregular periods), fatigue, pain during sexual activity, neurological symptoms (headaches, cognitive difficulties), psychosocial symptoms (mood, anxiety, sleep), and health-related quality of life domains (mental, physical, and social health). Secondary outcomes included participant demographic and clinical characteristics, patterns of GLP-1RA use (type, duration, side effects), changes in medication and alternative therapy use, full resolution of individual symptoms, experiences following treatment discontinuation, and qualitative feedback from open-ended responses. 2.3 Ethics and Data Collection The study received ethics approval from the Hamilton Health Sciences Research Ethics Board (Project ID: 18197). Prior to participation, individuals were presented with a Letter of Information describing the study purpose, risks, and voluntary nature of participation. Informed consent was implied by clicking “Submit” to proceed to the survey. All responses were anonymous. 2.4 Statistical Analysis Data were analyzed using IBM SPSS Statistics version 30 (IBM Corp., Armonk, NY, USA). Descriptive statistics are reported as frequencies, percentages, or mean ± standard deviation (SD). Paired-sample t tests were used to assess within-subject changes before and during GLP-1RA therapy. Symptom changes were evaluated using a 7-point Global Rating of Change scale (−3 = major worsening to +3 = complete improvement), with one-sample t tests and Cohen’s d used to assess statistical significance and effect sizes. Associations between percentage weight change and symptom change scores were explored using Spearman’s rank correlation coefficient (ρ). All tests were two-tailed with significance set at p < 0.05. Open-ended responses were analyzed using structured content analysis. Two reviewers (MG and NK) independently coded responses and grouped recurring concepts into themes. Discrepancies were resolved through discussion. Themes were summarized narratively and described in relation to how frequently they were reported. 3. Results 3.1 Participant Demographic Characteristics In total, 186 individuals initiated the survey. After eligibility screening and survey completion checks, 161 participants met inclusion criteria and were included in the final analysis. The average age was 35.8 ± 6.8 years. Most participants were based in Canada (55.9%) or the United States (23.6%), with others from Australia (10.6%), the UK (5%), and additional countries (Table 1). The majority identified as Caucasian (79.5%), followed by smaller proportions identifying as Mixed/Multicultural, West Asian, South Asian, and Indigenous backgrounds. Most participants had completed an undergraduate (37.9%) or postgraduate degree (30.4%). The majority were employed full time (68.3%), with others working part time (10.6%) or self-employed (7.5%) (Table 1). 3.2 Endometriosis History and Diagnostic Characteristics The majority of the participants (86.3%, n = 139) reported a confirmed diagnosis of endometriosis, and 13.7% (n = 22) reported suspected disease. Among suspected cases, common symptoms included menstrual pelvic pain (90.9%), gastrointestinal symptoms (86.4%), fatigue (86.4%), pain with bowel movements (81.8%), and dyspareunia (72.7%). Of those with confirmed diagnoses, 71.9% (n = 100) had surgical confirmation, 46.8% (n = 65) imaging-based, and 31.7% (n = 44) clinical diagnosis. Reported lesion types included deep endometriosis (54.0%), superficial endometriosis (39.6%), and ovarian endometriomas (37.4%). At survey completion, the most frequent symptoms were fatigue (83.9%), bloating (79.5%), lower back pain (76.4%), menstrual pain (71.4%), non-menstrual pelvic pain (69.6%), leg/hip/thigh pain (65.8%), and anxiety/stress (64.6%). Dyspareunia (63.4%) and infertility (29.2%) were also common, along with various gastrointestinal, urinary, neurological, and mood-related symptoms. Participants reported an average of 3.2 ± 2.0 comorbidities. The most common were anxiety/depression (44.1%), obesity (39.1%), adenomyosis (31.7%), Polycystic Ovary Syndrome (PCOS) (28.6%), infertility (24.2%), and IBS (22.4%) (Table S1). 3.3 Management Methods 65.8% (n=106) used medications to manage endometriosis symptoms and 60.2% (n=97) used alternative therapies. Patients used 1.4 ± 1.3 medications and 5.5 ± 3.6 alternative therapies on average. The most common medications were NSAIDs (78.3%), progestins (22.6%), and antidepressants or anti-anxiety medications (29.2%). The most common alternative therapies were heat therapy (74.2%), dietary changes (59.8%), and exercise (57.7%). The majority of participants (64%, n=103) reported having undergone at least one surgery for endometriosis. Among these, the average number of surgeries was 2.8 ± 1.3, with nearly half of the participants (48.5%, n = 50) reporting multiple surgeries. The most commonly reported surgical approach was laparoscopy (90.3%, n = 93) with excision of endometriosis lesions (67.0%, n = 69), and ablation (35.0%, n = 36) noted as the primary procedures performed (Table S2). 3.4 Patterns of GLP-1RAs Use and Treatment Impact Participants most commonly reported using semaglutide (75.2%, n=121), followed by tirzepatide (19.9%, n=32), liraglutide (8.7%, n=14), dulaglutide (1.9%, n=3), and albiglutide (0.6%, n=1). Reasons for GLP-1RAs use were predominantly weight loss (86.3%, n=139), with fewer citing type 2 diabetes (6.8%, n=11) and other indications, including prediabetic insulin resistance, PCOS, fertility concerns, inflammation, and suspected benefits for endometriosis-related symptoms (26.1%, n=42). The average duration of GLP-1RAs use was 10.7 ± 12.0 months, and the mean reported dose was 5.5 ± 21.5 mg/week. Overall, 67.1% (n=108) reported at least one side effect; the most frequent were decreased appetite (49.7%, n=80), nausea (47.2%, n=76), constipation (31.7%, n=51), acid reflux/heartburn (24.8%, n=40), and diarrhea (22.4%, n=36) (Table 2). Additionally, among participants who reported changes in their medication regimen following GLP-1RA use (28.2%, n=29/103) significant reduction was observed in the number of medications (2.59 ± 1.76 to 1.24 ± 0.74, d=0.85, p < 0.001) and alternative therapies used to manage endometriosis symptoms (5.09 ± 3.34 to 2.97 ± 2.66, d=0.59, p < 0.001). 3.5 Symptom Changes After GLP-1 Use Overall, 64.6% (n = 104) of respondents reported changes in at least one endometriosis-related symptom after starting GLP-1RAs therapy, alongside weight loss reported by 88.2% (n = 142). Consistent with these reports, participants experienced a significant reduction in body weight following GLP-1RA initiation, decreasing from 92.08 ± 22.39 kg to 80.01 ± 20.51 kg (mean difference 12.07 ± 14.56 kg; 95% CI 9.80–14.34, p < 0.001; Cohen’s d = 0.83). The most commonly improved symptoms were bloating or abdominal distention (endo belly) (59.6%, n = 62), lower back pain (37.5%, n = 39), non-menstrual pelvic pain (35.6%, n = 37), and pain during menstruation (34.6%, n = 36). Other frequently reported improvements included heavy or prolonged menstrual bleeding and/or irregular periods (29.8%, n = 31), leg/hip/thigh pain (26.0%, n = 27), and fatigue/low energy (18.3%, n = 19), with less common changes noted for bowel, urinary, sexual, and mood-related symptoms (Table S3). Statistically significant improvements were reported for bloating or abdominal distention (1.94 ± 1.42, p < 0.001, d = 1.42), heavy or prolonged menstrual bleeding and/or irregular periods (1.84 ± 1.49, p < 0.001, d = 1.49), non-menstrual pelvic pain (0.78 ± 1.33, p < 0.001, d = 0.78), menstrual pelvic pain (1.67 ± 1.24, p < 0.001, d = 1.67), lower back pain (1.54 ± 1.52, p < 0.001, d = 1.01), hip/leg/thigh pain (1.37 ± 1.45, p < 0.001, d = 0.95), and most troublesome symptom (1.34 ± 1.44, p < 0.001, d = 0.93) (Figure 1). Participants reported changes in health-related quality of life domains as well. Statistically significant improvements were observed in mental health (n=160, 1.21 ± 1.32, p < 0.001, d = 0.91), physical health (n=160, 1.34 ± 1.44, p < 0.001, d = 0.93), overall pain experience (n=158, 0.91 ± 1.35, p < 0.001, d = 0.67), social health (n=158, 1.24 ± 1.25, p < 0.001, d = 0.99), role functioning (n=158, 1.13 ± 1.22, p < 0.001, d = 0.93), general health perception (n=159, 1.52 ± 1.27, p < 0.001, d = 1.20), and overall quality of life (n=158, 1.46 ± 1.27, p < 0.001, d = 1.15) (Figure 2). Moreover, 33.7% (n=35) of those who reported symptom changes experienced complete resolution of at least one symptom following GLP-1RA therapy. The most frequently resolved symptoms were bloating or abdominal distention (42.9%, n = 15), lower back pain (28.6%, n = 10), and heavy or prolonged menstrual bleeding and/or irregular periods (28.6%, n = 10) (Table S4). Correlation analyses were conducted between percentage weight change and symptom domains that demonstrated statistically significant improvement following GLP-1RA use. Greater percentage weight reduction was significantly associated with greater improvement in non-menstrual pelvic pain (ρ = 0.262, p = 0.014), overall pain experience (ρ = 0.270, p < 0.001), and overall quality of life (ρ = 0.443, p < 0.001). No significant association was observed between percentage weight change and improvement in bloating or abdominal distention (ρ = −0.012, p = 0.924). 3.6 Discontinuation of GLP-1RAs A total of 36% (n = 58/161) of respondents reported discontinuing GLP-1RA therapy for an average of 6.57±10.46 months. The most frequently cited reasons for stopping treatment were difficulty adhering to the treatment (32.8%, n = 19), cost or insurance issues (27.6%, n = 16), and side effects (22.4%, n = 13). Less common reasons included a doctor’s recommendation (13.8%, n = 8), improvement in symptoms (1.7%, n = 1), and lack of improvement in symptoms (1.7%, n = 1). Among those who discontinued, 60.3% (n = 35) reported a recurrence of one or more endometriosis-related symptoms that had improved while using GLP-1RAs. The most commonly recurring symptoms were bloating or abdominal distention (62.9%, n = 22), lower back pain (57.1%, n = 20), and pain during menstruation (42.9%, n = 15). Other frequently recurring symptoms included non-menstrual pelvic pain (40.0%, n = 14), leg/hip/thigh pain (37.1%, n = 13), alternating bowel habits (34.3%, n = 12), and rectal pain and/or bleeding (34.3%, n = 12). Fatigue or low energy and anxiety/stress were each reported by 31.4% (n = 11) (Table S5). Lastly, participants who had discontinued GLP-1RA therapy reported deterioration in bloating or abdominal distention (−0.82 ± 2.06, p = 0.044, d = 0.34) and lower back pain (−1.47 ± 1.74, p = 0.002, d = 0.61). 3.7 Patient-Reported Experiences with GLP-1RA Use in Endometriosis A total of 59 participants provided open-text responses describing their experiences with GLP-1RAs for endometriosis. Thematic analysis identified six commonly reported categories (each mentioned by ≥10% of respondents): 1. Weight Loss and Body Image Improvements (45.8%, n = 27) 2. Pain and Menstrual Symptom Relief (16.9%, n = 10) 3. Hope, Empowerment, and Quality of Life (28.8%, n = 17) 4. Reflections on Treatment Adjustments and Tolerability (15.3%, n = 9) 5. Bloating and Gastrointestinal Symptom Relief (15.2%, n = 9) 6. Perceived Reduction in Inflammation (16.9%, n = 10) Additional themes included gastrointestinal side effects (3.4%, n = 2), fertility or cycle changes (8.5%, n = 5), uncertainty early in treatment (9.8%, n = 6), and health insurance and access barriers (8.5%, n = 5) (Table S6). 4. Discussion 4.1 Main findings This study explored the perceived effects of GLP-1RAs on endometriosis-related symptoms, treatment burden, and patient experiences. The majority of respondents reported meaningful symptom improvements after using GLP-1 receptor agonists (GLP-1RAs), with statistically significant changes observed in multiple pelvic and gastrointestinal symptoms, including bloating, menstrual and non-menstrual pelvic pain, lower back pain, and leg or hip pain. Improvements extended beyond symptom relief to include enhanced physical and mental health, reduced reliance on medications and alternative therapies, and increased overall quality of life. GLP-1RA use was also associated with significant weight reduction in this cohort, and greater percentage weight loss correlated with greater improvement in non-menstrual pelvic pain, overall pain experience, and overall quality of life. Many participants also described positive shifts in weight, body image, and personal empowerment, suggesting that the benefits of GLP-1RAs may extend beyond metabolic effects to encompass psychosocial dimensions of health. Importantly, over one-third of those who discontinued therapy experienced symptom recurrence, particularly bloating and lower back pain, underscoring the potential value of continued treatment. Together, these findings point to a possible adjunctive role for GLP-1RAs in managing endometriosis, especially among individuals with overlapping metabolic or inflammatory profiles. 4.2 Interpretation GLP-1RAs exert pleiotropic effects through several interconnected mechanisms, including modulation of inflammatory pathways, endocrine regulation, and neuro-immune signalling [10][19][16]. Their anti-inflammatory actions involve suppression of NF-κB signalling and reduced secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and C-reactive protein (CRP) [11][20]. In endometriosis, where peritoneal inflammation and macrophage activation are central to lesion persistence and pain, these effects could plausibly attenuate both lesion activity and nociceptive signalling, potentially contributing to the improvements observed across various pain, gastrointestinal, and menstrual symptoms in our cohort. Preclinical studies have also demonstrated that GLP-1 signalling enhances mitochondrial function and reduces reactive oxygen species [12], mechanisms increasingly implicated in endometriosis pathophysiology, including lesion persistence, fatigue, and neuronal sensitization [21]. By mitigating oxidative stress–driven neuronal sensitization, GLP-1RAs may help explain the improvements reported in fatigue, mental health, and overall quality of life in our cohort. Endocrine modulation is another plausible mechanism. In PCOS, GLP-1RAs have been associated with improved ovulatory function, lower serum androgens, and menstrual regularity [22][23]. While the hormonal milieu in endometriosis differs, alterations in gonadotropin secretion and progesterone resistance are common, and GLP-1-mediated improvements in insulin sensitivity and adipokine profiles could indirectly support more favourable steroidogenesis. The observed reduction in heavy or prolonged menstrual bleeding and reported improvements in cycle regularity may reflect hormonal stabilization via improved insulin sensitivity and adipokine profiles. GLP-1RA use was also associated with significant weight reduction, and greater percentage weight loss correlated with greater improvements in non-menstrual pelvic pain, overall pain experience, and overall quality of life. Adipose tissue functions as an active endocrine and inflammatory organ; therefore, reductions in adiposity may modulate systemic inflammation, insulin signaling, and adipokine balance in ways that influence pain perception and overall symptom burden [24][25]. Although several epidemiologic studies have reported an inverse association between BMI and surgically confirmed endometriosis [26], findings across populations and study designs have not been uniform [27][28]. BMI does not appear to significantly influence anatomical disease distribution and may instead shape aspects of clinical phenotype and symptom intensity [29]. This distinction underscores that epidemiologic patterns of disease prevalence are conceptually separate from metabolic influences on symptom expression once endometriosis is established. Collectively, these findings support a model in which GLP-1RAs may exert overlapping metabolic, endocrine, inflammatory, and neuro-immune effects, rather than acting solely through weight reduction. Neuro-immune modulation may also underlie the symptom relief we documented in pelvic and lower back pain, hip/leg/thigh pain, and overall pain experience. GLP-1RAs cross the blood–brain barrier, reduce microglial activation, and have demonstrated antinociceptive effects in animal models of chronic pain [16][30]. This is particularly relevant given the central sensitization and neuropathic pain features often present in endometriosis [31]. The recurrence of symptoms after discontinuation in our study parallels findings from obesity and diabetes trials, where cessation of GLP-1 therapy often leads to weight regain, deterioration in metabolic parameters, and increased inflammatory markers [32]. This suggests that ongoing therapy may be required for sustained benefits, though the optimal duration, dosing, and patient selection criteria in endometriosis remain unknown. Clinically, this study raises the possibility that GLP-1RAs could serve as a useful adjunct to conventional endometriosis therapies particularly for individuals with overlapping metabolic and endocrine conditions such as obesity or polycystic ovary syndrome [33][34][9]. Given their established benefits on weight reduction, insulin sensitivity, and hormonal regulation in these populations, their potential utility in endometriosis is biologically plausible. The observed reduction in both medications and alternative therapies suggests that GLP-1RA use may help alleviate broader treatment burden, including polypharmacy and associated healthcare system strain among individuals with endometriosis [35][36]. These downstream effects could translate into improvements in patient safety, adherence, and long-term care efficiency. However, widespread implementation faces challenges, including accessibility, affordability, and the current lack of long-term reproductive safety data [37]. These findings highlight the need to explore how GLP-1RAs might fit into broader endometriosis care models. Further investigation into their clinical role, safety profile, and potential mechanisms may inform future treatment strategies and support shared decision-making for patients with persistent or refractory symptoms. 4.3 Strengths and Limitations To our knowledge, this is the first study to systematically assess patient-reported use of GLP-1 receptor agonists in endometriosis, including treatment patterns, perceived symptom changes, and reasons for discontinuation. The survey combined structured multi-domain symptom rating scales, binary-response items, and open-ended questions. This multi-format approach enabled comprehensive capture of patient experiences, quantifying changes across diverse clinical domains while also eliciting nuanced perceptions and benefits not captured by predefined measures. While the cross-sectional, self-reported design provides valuable patient-centered insights, it is subject to recall bias and self-report limitations. Recruitment through online and clinical networks may have favored participation by individuals who are more engaged in their care or who experienced more noticeable changes. Additionally, the sample was predominantly Caucasian and from high-income countries, which may limit applicability to more diverse populations. 5. Conclusion This study provides patient-reported evidence that GLP-1RAs may improve key endometriosis-related symptoms, particularly pelvic pain, gastrointestinal discomfort, and overall quality of life, while reducing reliance on medications and alternative therapies. Benefits appeared to diminish after discontinuation, suggesting that ongoing treatment may be needed for sustained effect. These findings support continued investigation of GLP-1RAs as a potential adjunctive therapy for endometriosis. Prospective and mechanistic studies are warranted to clarify therapeutic mechanisms, identify subgroups most likely to benefit, and determine strategies for sustaining benefit after treatment cessation. Author Contributions M.G.: conceptualization, methodology, investigation, formal analysis, data curation, project administration, visualization, writing - original draft, writing - review and editing. N.K.: conceptualization, methodology, formal analysis, writing - review and editing. M.L.: supervision, methodology, writing - review and editing. Conflict of Interest ML reports grants from Australian MRFF, AbbVie, CanSAGE, Hamilton Health Sciences, Hyivy Health; honoraria for lectures/writing from AIUM, GE Healthcare, Bayer, AbbVie, TerSera, consultancy work with Hologic, Chugai, affiliations with Imagendo, outside the submitted work. MG and NK report no conflict of interest. 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Bars represent the mean change scores for symptoms with statistically significant improvement, and error bars indicate the standard error of the mean (SEM). Figure 2. Mean change in health-related quality of life domains following GLP-1RAs use. Participants rated change using a 7-point Global Rating of Change scale ranging from −3 (“major worsening”) to +3 (“complete improvement”). Bars represent the mean change score; error bars indicate standard error of the mean (SEM). Supplementary Material File (figure 1_glp-1_bjog.docx) Download 97.12 KB File (figure 2_glp-1_bjog.docx) Download 89.89 KB File (table 1_glp-1_bjog.docx) Download 16.13 KB File (table 2_glp-1_bjog.docx) Download 15.74 KB Information & Authors Information Version history V1 Version 1 24 February 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords endometriosis: drug treatment general gynaecology Authors Affiliations Mahsa Gholiof 0009-0003-6732-857X [email protected] McMaster University View all articles by this author Narges Kalani McMaster University View all articles by this author Mathew Leonardi McMaster University View all articles by this author Metrics & Citations Metrics Article Usage 2313 views 546 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Mahsa Gholiof, Narges Kalani, Mathew Leonardi. Effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Endometriosis Symptoms Management and Quality of Life: An International Survey Study. Authorea . 24 February 2026. DOI: https://doi.org/10.22541/au.177194722.27223197/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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