Self-Reported Use and Effectiveness of Marijuana for Pelvic Pain among Women with Endometriosis

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Methods A descriptive cross-sectional survey was undertaken using an anonymous online questionnaire to survey women with endometriosis about their experience with marijuana for management of pelvic pain: exploring symptom benefit, characteristics of use, and factors contributing to use and discontinuation. Participants were recruited from an outpatient gynecology clinic using endometriosis ICD-10 diagnostic codes - and from the Endometriosis Association mailing list. Results Marijuana use for symptom relief was reported by 78 (32.2%) Endometriosis Association participants, and 58 (46.8%) clinic participants. Within both populations, marijuana was considered very or moderately effective by most users (68.0–75.9%). Legality of recreational and medicinal marijuana in the state of residence was strongly associated with use (OR 7.13 [95%CI:2.57–19.8]). Among users specifying current or past use, discontinuation was reported by 45% (54 of 121), and most frequently attributed to non-clinical factors of legal/employment risk and obstacles to marijuana access; 64.8% of former users attributed discontinuation to non-clinical factors only. Lack of symptom relief from other clinical management was the most cited motivation for initiation (55.1% clinic, 39.7% EA users). Conclusion Marijuana use is common among women with endometriosis and chronic, refractory pelvic pain. Legality and access appear to impact use and discontinuation. While legal access to marijuana is associated with increased use, marijuana obtained outside of legal routes is also commonly being used for symptom relief. analgesia cannabis THC endometriosis pelvic pain Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Endometriosis is a common cause of chronic pelvic pain in women, for which there is no cure and high rates of pain recurrence despite treatment with surgery or hormone-related medication 1 . Dissatisfaction with current treatment is common, exhibited by 36% of Australian women in a recent study 2 , and use of alternative or self-care therapies for symptom management is common 2 , 3 . Basic science research shows that the pathophysiology of endometriosis may involve deficiency in the endocannabinoid system within female reproductive organs, with cannabinoid receptor 1 (CB1) mediating the anti-inflammatory effects of progesterone, but with reduced expression in patients with endometriosis 4 . Both Tetrahydrocannabinol (THC) (which activates CB1 and CB2 receptors) and CB1/CB2 cannabinoid receptor agonist WIN 55,212-2 have demonstrated anti-proliferative effects on stromal endometriotic cells, in vitro 5 and in a mouse model 56 . CB1 agonists have been shown to decrease endometriosis-associated pain in a rat model 7 . Taken together, these findings lend plausibility to the idea that cannabinoids could specifically benefit women with chronic pain related to endometriosis, a conclusion supported by several recent literature reviews 8 ,910 . The changing legal status of marijuana in many polities has led to increased availability, and evidence shows that endometriosis patients are exploring the use of endometriosis for management of pelvic pain. In Australia, where only medical marijuana is legal, 13% of 484 survey participants reported self-management with marijuana within the previous 6 months; average reported pain relief was 7.6 on a 0–10 scale 3 , 11 . An analysis of marijuana use for endometriosis symptom control among 252 Canadian users of a smart phone app for monitoring medical marijuana indicated treatment of pelvic pain as the most common reason for use (42.4% of sessions) 12 . A 2019 survey of 113 patients of a Florida specialty gynecologic clinic with pelvic and perineal pain, dyspareunia, or endometriosis reported marijuana use among 23% of respondents, with 96% of users reporting symptom improvement 13 . Recent literature reviews of marijuana-based medicine for endometriosis have concluded that data is limited and that more comprehensive research was required before use of cannabinoid compounds could be recommended or prescribed 14 - but all cross-sectional surveys on the topic have demonstrated that most marijuana users report pain relief with minimal side effects; so cannabinoids may be effective in relieving pain from numerous gynecologic conditions including endometriosis 15 . Despite broad availability of marijuana, clinical research on this topic is difficult to conduct due to legal restrictions, ethical concerns, and social stigma impacting participation. We therefore undertook an anonymized survey of women with endometriosis. We queried their experience with marijuana for management of endometriosis and pelvic pain symptoms, addressing perceived effectiveness; effects and side effects of use; and demographic, social and legal factors that may influence use. Methods A descriptive cross-sectional survey was conducted using an online anonymous questionnaire, in April and May 2019. This research was conducted at an academic-affiliated private gynecologic clinic in Arizona that is a referral center for evaluation and treatment of chronic pelvic pain. Invitations to participate were distributed to two populations: 1) clinic patients seen over a two year period (from 1/1/2017 to 12/31/2018) with an endometriosis ICD-10 diagnostic code (N80.0 through N80.9) in their electronic medical record and an email address listed in the electronic medical record, and 2) members of the Endometriosis Association (EA) support group mailing list. Participants were asked to attest to being a woman 18 years of age or older with a diagnosis of endometriosis. Postmenopausal patients were not excluded from participation as survey inquired about historic use of marijuana for endometriosis symptoms. The anonymous survey entailed an original structured questionnaire with 55 to 75 questions with adaptive questioning, distributed over 9 to 11 pages. The instrument queried pelvic pain symptoms, treatment history, marijuana use, demographic factors, and comorbidities. The survey was developed and revised with testing of the electronic questionnaire functionality and face validity of the content by physician researchers and pilot patients drawn from the leadership of the Endometriosis Association. Recruitment was initiated by sending an email solicitation that described the study purpose, participation criteria, anticipated 10–30 minute survey length, and assurance of the anonymous nature of this survey. The email solicitation included a hyperlink to the REDCap open survey; the email solicitation was resent one week later. The survey remained open for one month. No incentive was offered for study participation, as this would have been difficult to administer anonymously. IP address of the client computer was not collected to preserve the anonymity of study participants. An online introduction page provided information on the investigator identity and study purpose, and a statement of informed consent describing risks and benefits to participants. The institutional IRB granted a waiver of consent to avoid any risk to privacy from linking de-identified data with identifiers that would be required to document consent. Study data were collected and managed using REDCap electronic data capture tools hosted at Barrows/Dignity Health 16 , 17 . Email invitations to participate were sent to 701 clinic patients, with 19.5% (137) initiating the survey and 17.7% (124) completing the survey. Email invitations to participate were sent to 24,259 email addresses through the EA support group mailing list, with 1.5% (352) initiating and 1.0% (249) completing the survey, including two international participants. Participants who completed > 75% of data items were included in survey analysis. Missing data resulted from questions to which no multiple-choice answer was selected, or from free-text answers that were missing or incomprehensible (e.g. years of pain duration indicated > 100). For each statistical analysis, respondents missing data for the examined variable were excluded. The multivariate analysis excluded any participants with missing data for the variables included in the analysis. In descriptive analyses we tabulated demographic factors; comorbidities; use of alcohol, tobacco, and recreational drugs; and legality of marijuana in the state where each woman resided. We summarized counts and proportions for participants in the clinic and EA groups and for the total sample. We used independent sample t-tests and Pearson’s chi-squared tests to compare characteristics of marijuana users vs non-users in each group (clinic, EA, total), and reported age at time of the survey and duration of pelvic pain using means and standard deviations. A binary variable was created to indicate lifetime use of marijuana for the relief of pain. Participants who answered “Yes, in the past”, or “Yes, currently” to the question “Have you used marijuana for medicinal purposes, such as relief from chronic pain?” were coded as “Yes” to ever having used marijuana. To account for missing data, if a participant declined to reply to the aforementioned question but indicated that she had used marijuana for relief of chronic pelvic pain through her response to a separate effectiveness question “What treatments have you attempted with the specific goal of helping relieve your endometriosis / chronic pelvic pain, and how well have they worked?”, participants who rated the effectiveness of “marijuana/cannabis/THC”, instead of indicating “Have Never Tried” as a response were also coded “Yes” for lifetime marijuana use (15 survey participants). Throughout this manuscript, unless otherwise specified, “use” refers to use of marijuana for symptom relief. Participants were asked to rate treatments, including “Marijuana/Cannabis/THC” and “Cannabidiol (CBD) (without THC) products” as “Not effective”, “Slightly effective”, “Moderately effective”, “Very effective”, or “Have Never Tried” for relief of endometriosis/chronic pelvic pain. Among those who reported using marijuana we also examined frequency and duration of use, legality in state of use, possession of a medical marijuana card, use in pregnancy, symptoms treated, side effects, methods of obtaining marijuana, and reasons for initiation and cessation of use. We used logistic regression to estimate univariate associations between ever using marijuana for relief of pain (yes, no) and each aforementioned demographic and legality variable, and variables such as sexuality, use of substances other than marijuana, and co-morbidities. We estimated univariate associations separately for clinic and EA groups; finding results to be similar we estimated these associations for the total sample by introducing an indicator for group (clinic, EA). To construct the final models, we used a purposeful selection method 18 in which variables with a bivariate p-value of < 0.25 were included for further multivariate analysis. This process identified age (years), lifetime recreational drug use, lifetime tobacco use, sleep problems, participant-perceived legality of marijuana in her state, education, and employment as variables retained in the multivariate model. Likelihood ratio tests and p-values were used to assess deletion of variables and model fit. The final multivariable models were checked for goodness of fit and explained variance. We used SPSS Version 25 to implement all analyses. A p-value of 0.05% or less was used to define statistical significance. Results Participants who completed the survey ranged from 18 to 70 years of age. Menopausal status was not interrogated, but using age as a proxy, 80.1% of respondents indicated age 50 (likely post-menopausal). Those in the clinic group tended to be younger than those in the EA group (mean ages 33.1 versus 46.9 years); in both groups women who reported using marijuana were younger than those who did not. Participants in both groups reported long histories of pain, but average duration was shorter in the clinic group (12.5 versus 23.3 years). Additional demographic features of participants are reported in Table 1. Use of marijuana for symptom relief was reported by 45.1% of clinic participants, 23.8% reporting current and 21.3% past use. Such use was reported by 28.3% of EA participants, 16.3% reporting current and 12.0% past use. In both groups those who reported current or past marijuana use were more likely to report possessing a marijuana card; residing where medical use of marijuana was legal; and using CBD (without THC), other recreational drugs, and tobacco. Reported substance use is described in Table 2. Multivariate analysis identified factors most strongly associated with using marijuana for symptom relief. Use was much more common in young women and estimated to be 7–9% lower for each year of participants’ age at the time of participation. In addition, use was nearly 6-fold greater in women with a history of recreational drug use than in those without (adjusted OR 5.77 (95% CI 2.90, 11.49). Compared to those who reported living where all marijuana use was illegal, use was 3-fold greater in those living in states where medical marijuana use was legal (adjusted OR 3.04 (95% CI 1.29, 7.17) and 7-fold greater for those in states where recreational use was legal (adjusted OR 7.13 (95% CI 2.57, 19.81). Use was also 2- to 3-fold greater in those who did not finish college, those with a disability preventing work, and those who reported sleep difficulties. Detailed results of multi-variate analysis are provided in Table 4. Characteristics of women who reported marijuana use are provided in Table 5. The majority of participants in the clinical group lived in Arizona, where only medical marijuana was legal at the time of the survey; all users in this group correctly identified the legal status of marijuana in their state. Within the EA group legal status of marijuana in the participant’s state varied: 17.6% reported living where marijuana use was not legal for any purpose, 37.8% where legal only for medical use, and 34.6% where legal for recreational use. Accordingly, source for marijuana differed between the two survey populations (Fig. 1). Figure 1. Cannabis Source Those in the clinic population most often obtained it directly through a dispensary (63.3%), while those in the EA group were more likely to obtain it from a friend or family member (51.7%, versus 41.4% from a dispensary directly). Large proportions in both groups (46.4% clinic, 74.0% EA) had never obtained a physician-issued medical marijuana card. Among users residing in a state where only medical marijuana was legal, 52.3% (n = 23) of current users reported having a medical marijuana card. Frequency of marijuana use had a bimodal distribution (Table 5): most common responses were several times per day (22.4% clinic, 14.1% EA users) and less than once per month (20.7% clinic, 16.7% EA users). Regarding interaction with fertility-related factors, use throughout pregnancy was uncommon, reported by only 1 clinic user (1.7%) and 3 EA users (3.8%). Among marijuana users, 34.6% (n = 47) reported having undergone hysterectomy to address their endometriosis pain. Although participants reported using marijuana to treat a variety of symptoms, they most often reported use for treatment of constant pelvic pain (86.3% clinic, 75.4% EA users) (Fig. 2 ). Numerous respondents identified multiple reasons for use, and anxiety or depression (64.7% clinic, 55.7% EA users) and difficulty sleeping (76.5% clinic, 54.1% EA users) were frequently noted. Reasons for initiating use varied between the populations (Fig. 3). Figure 3. Reason for trying cannabis Lack of symptom relief from other clinical management was the single most cited motivation for initiation (55.1% clinic, 39.7% EA users). The recommendation to try marijuana was reported to come predominantly from social contacts -- friends, family, or other patients (89.8% clinic, 82.8% EA users). Recommendation of a physician was infrequently reported (12.2% clinic, 20.7% EA users). The majority of users reported marijuana to be very or moderately effective for relief of endometriosis/chronic pelvic pain (75.9% clinic, 68.0% EA users). Notably, marijuana was most often considered very effective (53.4% clinic, 39.7% EA users). Routes of administration reported to be most effective were smoked/inhaled (29.2% clinic, 43.1% EA users) and edibles (31.3% clinic, 36.2% EA users). Use by more than one route was reported by 75.7% of users. Among all women who reported using marijuana, those who obtained it directly from a dispensary tended to report greater effectiveness (moderately effective or very effective vs not effective or slightly effective; total sample, p = 0.009; clinic, p = 0.006; EA, p = 0.374 ) However, within the EA group, those who obtained it from friends or family tended to report greater effectiveness (moderately effective or very effective vs not effective or slightly effective; total sample, p = 0.097, clinic, p = 0.403, EA, p = 0.005). The most frequently reported side effects of marijuana were comparatively mild. Most users reported experiencing dry mouth (65.9% clinic, 63.5% EA users) and increased appetite (61.0% clinic, 71.2% EA users) (Fig. 4 ). Among the 54 women who stopped using marijuana, discontinuation was attributed to several reasons (Fig. 5). Figure 5: Reasons for discontinuing cannabis Collectively, non-clinical factors such as employment or legal risk, social stigma, or obstacles to access were most commonly cited. Lack of effectiveness for symptom control was cited by 42.9% of clinic past users and 30.4% of EA past users. Unpleasant side effects were cited by 23.8% of clinic past users and 26.1% of EA past users. The majority of past users 64.8%) attributed discontinuation to only non-clinical factors, with neither lack of symptom control nor unpleasant side effects cited. Use of cannabidiol without THC was reported by 27.8% (67 of 240) EA participants, with half (50%, 34 of 67) reporting CBD to be very or moderately effective. Use was reported by 46.0% of clinic participants (57 of 124), with the majority (64.9%, 37 of 57) reporting CBD to be very or moderately effective. CBD was most likely to be reported as moderately effective (31.4% of EA participants, 36.8% of clinic participants). Of the 127 patients reporting cannabidiol use, 99 (78%) also reported marijuana use. Discussion Marijuana use for self-management of endometriosis pain was more common among younger survey participants and in states with less legal restrictions to access; this finding corroborates those of earlier surveys and suggests that prevalence of use may continue to increase with broader decriminalization of marijuana and as a result of generational differences in attitudes towards marijuana. Illegal use of marijuana is common, reported by 52.3% of current users within a state where only medicinal use is legal – but this is lower than 80% of users reported in a previous Florida-based survey 13 . Two predominant patterns of marijuana use were reported: as a rescue pain medication for use once per month, which may represent a strategy for dealing with pain associated with menses or other painful flares – alternatively as a continuous medication used daily and multiple times per day. Future interventional clinical studies may benefit from focusing on the first pattern of use, as risks from marijuana use would likely be anticipated to be less when used sparingly. Beyond management of pelvic pain, users indicated improved mood and sleep as addition symptoms treated with marijuana, so future interventional studies could include these as secondary outcomes. Dissatisfaction with symptom relief from other therapies was the most cited reason for initiating marijuana, highlighting patients’ experience of inadequacy of current therapies for management of endometriosis and chronic pelvic pain: for these patients, marijuana was being used to treat chronic refractory pelvic pain. Initiation of marijuana is predominantly due to advisement by lay person social networks outside of the medical establishment. Discontinuation of marijuana use was reported by approximately half of users, despite most reporting effective relief of their pelvic pain symptoms with marijuana. While a minority of past users discontinued marijuana due to clinical factors of poor symptom relief or unpleasant side effects, the majority of past users exclusively cited non-clinical reasons for discontinuation: loss of access, social taboo, legal/employment risk. This result mirrors findings from our multivariate analysis that legal access to marijuana is the factor most associated with increased marijuana use. Together, these results identify social and legal factors as likely determinants of use by women with endometriosis and pelvic pain. Our findings reflect those of an international survey of 1,179 endometriosis patients, which identified legality, access, and employment concerns as reasons for discontinuation of marijuana, with a higher proportion of survey respondents reporting marijuana use from countries with legal access. A similar trend was noted elsewhere as a result of legalization of recreational marijuana in Canada (through retrospective chart review, a change from 13.3% users prior to legalization, to 21.5% users after legalization) 19 . Low participation is a limitation of our survey, making the data vulnerable to response bias if those who did or did not use marijuana were less likely to participate; estimates of prevalence of marijuana use should be interpreted considering this caution. However, it seems less likely that participation would be influenced by both use and reasons for use, or use and consequences of use. The factors found by this study to be associated with use are therefore unlikely to be spurious consequences of response bias. Because the total number of marijuana users was large, results are unlikely to represent random error. Concern about legal risk and social taboo likely contributed to low participation and to missing data, especially among the EA group; the clinic group may have had somewhat higher participation due to familiarity with and trust in the researchers and sponsoring institution. Additional limitations are that the survey questionnaire was not validated, and that the diagnosis of endometriosis was not based on pathology confirmation. In the EA group the endometriosis diagnosis was self-reported, and in the clinic group the diagnosis may have been made clinically, without surgical confirmation. Although it seems unlikely that significant numbers of women without endometriosis would have been included, a small proportion of participants may have reported on their experience with a less specific cause of pelvic pain. Conclusions Endometriosis is a common, incurable cause of chronic pelvic pain in women and many patients report dissatisfaction with available treatment options. Marijuana represents a unique and reportedly effective option for symptom management, but access is variable and limited by social and legal factors. Prevalence of marijuana use among endometriosis patients appears to be most determined by legal and social rather than clinical factors, with discontinuation common despite reported effectiveness. Within the changing legal climate across the United States, our data suggest that the number of women who will try marijuana for management of endometriosis and pelvic pain is likely to increase in the future. Variability in legal access to this potentially beneficial treatment option contributes to inequities in chronic pain symptom relief among the diverse population of individuals affected by endometriosis. In choosing to study the use of cannabis within a population containing young women and individuals with reproductive capacity, we recognize and do not seek to obscure the potential harms of cannabis use, including the unique morbidity associated with prenatal use of cannabis. We also recognize the vulnerability of this population and the significant lifelong morbidity resulting from chronic, largely refractory pain that develops in the second or third decade of life. For a population whose care may be colored by bias related to fertility capacity and goals, we sought to objectively evaluate and present data on use of cannabis. Our data indicate a history of a sterilizing procedure among one third of cannabis users, and use within pregnancy was rare. Results of this observational study may inform future interventional studies in which use of marijuana products to alleviate chronic pelvic pain symptoms in women with endometriosis could be assessed in a far more controlled fashion. Future research including interventional trials could seek to minimize variability in marijuana strain, route, dose, and frequency of use, to better ascertain the relationship of these factors to effectiveness of symptom relief and adverse side effects. Abbreviations EA - Endometriosis Association Declarations Acknowledgements Acknowledgements: Endometriosis Association, Dignity Health St. Joseph's Minimally Invasive Gynecologic Surgery Fellowship - Ethical Approval and Consent to participate IRB approval obtained 12/17/2018, #PHX-18-500-169-73-21, St Joseph’s Hospital and Medical Center, Institutional Review Board Panel A, 350 W Thomas Rd, Phoenix, AZ 85013 - Funding Financial support for survey dissemination by Dignity Health Medical Group, Department of OB/GYN, Advanced Gynecologic Surgery Division - Conflicts of interest/Competing interests The authors report no conflicts of interest. Data Availability The data that support the findings of this study are available from the corresponding author, upon reasonable request. - Code availability N/A Authors' contributions AR contributed to conception and design of study, data collection/patient recruitment. 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Ann Transl Med . 2016;4(6). doi:10.21037/atm.2016.02.15 Geoffrion R, Yang EC, Koenig NA, et al. Recreational Cannabis Use Before and After Legalization in Women With Pelvic Pain. Obstetrics and gynecology . 2021;137(1):91-99. doi:10.1097/AOG.0000000000004207 Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.png Table 1 Table2.png Table 2 Table3.png Table 3 Table4.png Table 4 Table5.png Table 5 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4536326","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321757404,"identity":"edae5862-d004-4711-8862-fbd75e6bb694","order_by":0,"name":"Anna Reinert","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYBADHjD5gYGBsQEiwEyUFsbGGaRoAQHGZh5itPDP7j34gXGPjYw5e+/zx7Y5NrINEukPPzBUWCc24NAicedcsgTDszQey57jhs2529KMGyRyjCUYzqTj1MJwI8dAguHAYR6DG2mMQC2HE4Fa2BgY2w7j1CJ/I8f4B8OB/zwG958xNltu+w/Ukv6MgfEfbi0GN3LMgLYcANrCxtjMuO0AUEuCGTAQcGsxBGqxSDiQzGNwJo1xZu+2ZOM2njfGEgnH0o1xaZEDOuzGhwN29gbHjzF8+LnNTrafHRhiH2qsZXF6HwQSkDlsGCKjYBSMglEwCkgGAL2HV+Fl9ZIcAAAAAElFTkSuQmCC","orcid":"","institution":"University of Southern California","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Reinert","suffix":""},{"id":321757405,"identity":"63a43b7a-93fe-4335-88fe-666beb5678be","order_by":1,"name":"Maria Bolshakova","email":"","orcid":"","institution":"University of Southern California","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Bolshakova","suffix":""},{"id":321757406,"identity":"d5b73ad1-a4a3-40b3-ac5f-b494ada42219","order_by":2,"name":"Victoria Cortessis","email":"","orcid":"","institution":"University of Southern California","correspondingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"","lastName":"Cortessis","suffix":""},{"id":321757407,"identity":"78723e94-4aaf-4ae2-8b22-2418b0334b34","order_by":3,"name":"Alexander Wong","email":"","orcid":"","institution":"RAND Corporation","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Wong","suffix":""}],"badges":[],"createdAt":"2024-06-05 22:10:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4536326/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4536326/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60436335,"identity":"50a3a50e-a1cc-4709-b730-ded06b15b772","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51746,"visible":true,"origin":"","legend":"\u003cp\u003eCannabis Source\u003c/p\u003e","description":"","filename":"Figure1Revised.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/fecfd59171176f79a8654341.png"},{"id":60436336,"identity":"2cb83412-421b-4052-a130-a2e38e7b094a","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53111,"visible":true,"origin":"","legend":"\u003cp\u003eSymptoms treated with cannabis\u003c/p\u003e","description":"","filename":"Figure2Revised.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/80281285637fba8072e77112.png"},{"id":60436337,"identity":"85e7f015-f2f2-4c4c-aba9-da5ce9e97f62","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51836,"visible":true,"origin":"","legend":"\u003cp\u003eReason for trying cannabis\u003c/p\u003e","description":"","filename":"Figure3Revised.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/d2f8461353c5c16e650ef15b.png"},{"id":60436339,"identity":"88406f92-b385-4a56-bdc5-76c86a07f22e","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":51779,"visible":true,"origin":"","legend":"\u003cp\u003eSide effects of cannabis use\u003c/p\u003e","description":"","filename":"Figure4Revised.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/c73516af3467f27bc4d3ef62.png"},{"id":60436338,"identity":"2707ed89-0669-4e13-a460-2766515eb3c2","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":62558,"visible":true,"origin":"","legend":"\u003cp\u003eReasons for discontinuing cannabis\u003c/p\u003e","description":"","filename":"Figure5Revised.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/1e76b5706f16661212bfb586.png"},{"id":65142489,"identity":"634db9cf-a150-4ef6-af1b-b9ccedea0a8d","added_by":"auto","created_at":"2024-09-24 05:39:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":551510,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/a7243c5f-2784-4a2b-90b6-fe855c5c2bc2.pdf"},{"id":60437301,"identity":"de9482a7-e45c-4a94-aa64-07ae0998900d","added_by":"auto","created_at":"2024-07-16 17:40:57","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":369114,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1\u003c/p\u003e","description":"","filename":"Table1.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/166e5b186f6bee83249e42ba.png"},{"id":60436341,"identity":"e2d664b6-1699-4a51-957e-96ead49778a2","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":268852,"visible":true,"origin":"","legend":"\u003cp\u003eTable 2\u003c/p\u003e","description":"","filename":"Table2.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/9ab7783f47302d5f475fd176.png"},{"id":60436344,"identity":"d3fba52a-473b-4766-a7fa-9e95410b34f5","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":297357,"visible":true,"origin":"","legend":"\u003cp\u003eTable 3\u003c/p\u003e","description":"","filename":"Table3.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/e5956468016843eec6f4816f.png"},{"id":60437302,"identity":"350def27-a715-4cad-ae0f-afc00d9a4c1b","added_by":"auto","created_at":"2024-07-16 17:40:57","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":278715,"visible":true,"origin":"","legend":"\u003cp\u003eTable 4\u003c/p\u003e","description":"","filename":"Table4.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/3fabfdbf2b35bb4ba950c93d.png"},{"id":60436342,"identity":"0dbf96ea-e6c3-476d-961a-ae535df4362d","added_by":"auto","created_at":"2024-07-16 17:32:57","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":338691,"visible":true,"origin":"","legend":"\u003cp\u003eTable 5\u003c/p\u003e","description":"","filename":"Table5.png","url":"https://assets-eu.researchsquare.com/files/rs-4536326/v1/20ae9422402e14d03a62c919.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Self-Reported Use and Effectiveness of Marijuana for Pelvic Pain among Women with Endometriosis","fulltext":[{"header":"Background","content":"\u003cp\u003eEndometriosis is a common cause of chronic pelvic pain in women, for which there is no cure and high rates of pain recurrence despite treatment with surgery or hormone-related medication \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Dissatisfaction with current treatment is common, exhibited by 36% of Australian women in a recent study \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, and use of alternative or self-care therapies for symptom management is common\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Basic science research shows that the pathophysiology of endometriosis may involve deficiency in the endocannabinoid system within female reproductive organs, with cannabinoid receptor 1 (CB1) mediating the anti-inflammatory effects of progesterone, but with reduced expression in patients with endometriosis \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Both Tetrahydrocannabinol (THC) (which activates CB1 and CB2 receptors) and CB1/CB2 cannabinoid receptor agonist WIN 55,212-2 have demonstrated anti-proliferative effects on stromal endometriotic cells, in vitro \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e and in a mouse model\u003csup\u003e56\u003c/sup\u003e. CB1 agonists have been shown to decrease endometriosis-associated pain in a rat model \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Taken together, these findings lend plausibility to the idea that cannabinoids could specifically benefit women with chronic pain related to endometriosis, a conclusion supported by several recent literature reviews \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,910\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe changing legal status of marijuana in many polities has led to increased availability, and evidence shows that endometriosis patients are exploring the use of endometriosis for management of pelvic pain. In Australia, where only medical marijuana is legal, 13% of 484 survey participants reported self-management with marijuana within the previous 6 months; average reported pain relief was 7.6 on a 0–10 scale \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. An analysis of marijuana use for endometriosis symptom control among 252 Canadian users of a smart phone app for monitoring medical marijuana indicated treatment of pelvic pain as the most common reason for use (42.4% of sessions)\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. A 2019 survey of 113 patients of a Florida specialty gynecologic clinic with pelvic and perineal pain, dyspareunia, or endometriosis reported marijuana use among 23% of respondents, with 96% of users reporting symptom improvement\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Recent literature reviews of marijuana-based medicine for endometriosis have concluded that data is limited and that more comprehensive research was required before use of cannabinoid compounds could be recommended or prescribed\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e - but all cross-sectional surveys on the topic have demonstrated that most marijuana users report pain relief with minimal side effects; so cannabinoids may be effective in relieving pain from numerous gynecologic conditions including endometriosis\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite broad availability of marijuana, clinical research on this topic is difficult to conduct due to legal restrictions, ethical concerns, and social stigma impacting participation. We therefore undertook an anonymized survey of women with endometriosis. We queried their experience with marijuana for management of endometriosis and pelvic pain symptoms, addressing perceived effectiveness; effects and side effects of use; and demographic, social and legal factors that may influence use.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eA descriptive cross-sectional survey was conducted using an online anonymous questionnaire, in April and May 2019. This research was conducted at an academic-affiliated private gynecologic clinic in Arizona that is a referral center for evaluation and treatment of chronic pelvic pain. Invitations to participate were distributed to two populations: 1) clinic patients seen over a two year period (from 1/1/2017 to 12/31/2018) with an endometriosis ICD-10 diagnostic code (N80.0 through N80.9) in their electronic medical record and an email address listed in the electronic medical record, and 2) members of the Endometriosis Association (EA) support group mailing list. Participants were asked to attest to being a woman 18 years of age or older with a diagnosis of endometriosis. Postmenopausal patients were not excluded from participation as survey inquired about historic use of marijuana for endometriosis symptoms. The anonymous survey entailed an original structured questionnaire with 55 to 75 questions with adaptive questioning, distributed over 9 to 11 pages. The instrument queried pelvic pain symptoms, treatment history, marijuana use, demographic factors, and comorbidities. The survey was developed and revised with testing of the electronic questionnaire functionality and face validity of the content by physician researchers and pilot patients drawn from the leadership of the Endometriosis Association. Recruitment was initiated by sending an email solicitation that described the study purpose, participation criteria, anticipated 10–30 minute survey length, and assurance of the anonymous nature of this survey. The email solicitation included a hyperlink to the REDCap open survey; the email solicitation was resent one week later. The survey remained open for one month. No incentive was offered for study participation, as this would have been difficult to administer anonymously. IP address of the client computer was not collected to preserve the anonymity of study participants. An online introduction page provided information on the investigator identity and study purpose, and a statement of informed consent describing risks and benefits to participants. The institutional IRB granted a waiver of consent to avoid any risk to privacy from linking de-identified data with identifiers that would be required to document consent. Study data were collected and managed using REDCap electronic data capture tools hosted at Barrows/Dignity Health\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eEmail invitations to participate were sent to 701 clinic patients, with 19.5% (137) initiating the survey and 17.7% (124) completing the survey. Email invitations to participate were sent to 24,259 email addresses through the EA support group mailing list, with 1.5% (352) initiating and 1.0% (249) completing the survey, including two international participants. Participants who completed \u0026gt; 75% of data items were included in survey analysis. Missing data resulted from questions to which no multiple-choice answer was selected, or from free-text answers that were missing or incomprehensible (e.g. years of pain duration indicated \u0026gt; 100). For each statistical analysis, respondents missing data for the examined variable were excluded. The multivariate analysis excluded any participants with missing data for the variables included in the analysis.\u003c/p\u003e\u003cp\u003eIn descriptive analyses we tabulated demographic factors; comorbidities; use of alcohol, tobacco, and recreational drugs; and legality of marijuana in the state where each woman resided. We summarized counts and proportions for participants in the clinic and EA groups and for the total sample. We used independent sample t-tests and Pearson’s chi-squared tests to compare characteristics of marijuana users vs non-users in each group (clinic, EA, total), and reported age at time of the survey and duration of pelvic pain using means and standard deviations.\u003c/p\u003e\u003cp\u003eA binary variable was created to indicate lifetime use of marijuana for the relief of pain. Participants who answered “Yes, in the past”, or “Yes, currently” to the question “Have you used marijuana for medicinal purposes, such as relief from chronic pain?” were coded as “Yes” to ever having used marijuana. To account for missing data, if a participant declined to reply to the aforementioned question but indicated that she had used marijuana for relief of chronic pelvic pain through her response to a separate effectiveness question “What treatments have you attempted with the specific goal of helping relieve your endometriosis / chronic pelvic pain, and how well have they worked?”, participants who rated the effectiveness of “marijuana/cannabis/THC”, instead of indicating “Have Never Tried” as a response were also coded “Yes” for lifetime marijuana use (15 survey participants). Throughout this manuscript, unless otherwise specified, “use” refers to use of marijuana for symptom relief.\u003c/p\u003e\u003cp\u003eParticipants were asked to rate treatments, including “Marijuana/Cannabis/THC” and “Cannabidiol (CBD) (without THC) products” as “Not effective”, “Slightly effective”, “Moderately effective”, “Very effective”, or “Have Never Tried” for relief of endometriosis/chronic pelvic pain. Among those who reported using marijuana we also examined frequency and duration of use, legality in state of use, possession of a medical marijuana card, use in pregnancy, symptoms treated, side effects, methods of obtaining marijuana, and reasons for initiation and cessation of use.\u003c/p\u003e\u003cp\u003eWe used logistic regression to estimate univariate associations between ever using marijuana for relief of pain (yes, no) and each aforementioned demographic and legality variable, and variables such as sexuality, use of substances other than marijuana, and co-morbidities. We estimated univariate associations separately for clinic and EA groups; finding results to be similar we estimated these associations for the total sample by introducing an indicator for group (clinic, EA). To construct the final models, we used a purposeful selection method\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e in which variables with a bivariate p-value of \u0026lt; 0.25 were included for further multivariate analysis. This process identified age (years), lifetime recreational drug use, lifetime tobacco use, sleep problems, participant-perceived legality of marijuana in her state, education, and employment as variables retained in the multivariate model. Likelihood ratio tests and p-values were used to assess deletion of variables and model fit. The final multivariable models were checked for goodness of fit and explained variance. We used SPSS Version 25 to implement all analyses. A p-value of 0.05% or less was used to define statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eParticipants who completed the survey ranged from 18 to 70 years of age. Menopausal status was not interrogated, but using age as a proxy, 80.1% of respondents indicated age\u0026thinsp;\u0026lt;\u0026thinsp;50 (likely premenopausal), and 11.0% indicated age\u0026thinsp;\u0026gt;\u0026thinsp;50 (likely post-menopausal). Those in the clinic group tended to be younger than those in the EA group (mean ages 33.1 versus 46.9 years); in both groups women who reported using marijuana were younger than those who did not. Participants in both groups reported long histories of pain, but average duration was shorter in the clinic group (12.5 versus 23.3 years). Additional demographic features of participants are reported in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eUse of marijuana for symptom relief was reported by 45.1% of clinic participants, 23.8% reporting current and 21.3% past use. Such use was reported by 28.3% of EA participants, 16.3% reporting current and 12.0% past use. In both groups those who reported current or past marijuana use were more likely to report possessing a marijuana card; residing where medical use of marijuana was legal; and using CBD (without THC), other recreational drugs, and tobacco. Reported substance use is described in Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMultivariate analysis identified factors most strongly associated with using marijuana for symptom relief. Use was much more common in young women and estimated to be 7\u0026ndash;9% lower for each year of participants\u0026rsquo; age at the time of participation. In addition, use was nearly 6-fold greater in women with a history of recreational drug use than in those without (adjusted OR 5.77 (95% CI 2.90, 11.49). Compared to those who reported living where all marijuana use was illegal, use was 3-fold greater in those living in states where medical marijuana use was legal (adjusted OR 3.04 (95% CI 1.29, 7.17) and 7-fold greater for those in states where recreational use was legal (adjusted OR 7.13 (95% CI 2.57, 19.81). Use was also 2- to 3-fold greater in those who did not finish college, those with a disability preventing work, and those who reported sleep difficulties. Detailed results of multi-variate analysis are provided in Table\u0026nbsp;4. Characteristics of women who reported marijuana use are provided in Table\u0026nbsp;5. \u003c/p\u003e \u003cp\u003eThe majority of participants in the clinical group lived in Arizona, where only medical marijuana was legal at the time of the survey; all users in this group correctly identified the legal status of marijuana in their state. Within the EA group legal status of marijuana in the participant\u0026rsquo;s state varied: 17.6% reported living where marijuana use was not legal for any purpose, 37.8% where legal only for medical use, and 34.6% where legal for recreational use. Accordingly, source for marijuana differed between the two survey populations (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eFigure 1. Cannabis Source\u003c/p\u003e \u003cp\u003e Those in the clinic population most often obtained it directly through a dispensary (63.3%), while those in the EA group were more likely to obtain it from a friend or family member (51.7%, versus 41.4% from a dispensary directly). Large proportions in both groups (46.4% clinic, 74.0% EA) had never obtained a physician-issued medical marijuana card. Among users residing in a state where only medical marijuana was legal, 52.3% (n\u0026thinsp;=\u0026thinsp;23) of current users reported having a medical marijuana card.\u003c/p\u003e \u003cp\u003eFrequency of marijuana use had a bimodal distribution (Table\u0026nbsp;5): most common responses were several times per day (22.4% clinic, 14.1% EA users) and less than once per month (20.7% clinic, 16.7% EA users). Regarding interaction with fertility-related factors, use throughout pregnancy was uncommon, reported by only 1 clinic user (1.7%) and 3 EA users (3.8%). Among marijuana users, 34.6% (n\u0026thinsp;=\u0026thinsp;47) reported having undergone hysterectomy to address their endometriosis pain.\u003c/p\u003e \u003cp\u003eAlthough participants reported using marijuana to treat a variety of symptoms, they most often reported use for treatment of constant pelvic pain (86.3% clinic, 75.4% EA users) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNumerous respondents identified multiple reasons for use, and anxiety or depression (64.7% clinic, 55.7% EA users) and difficulty sleeping (76.5% clinic, 54.1% EA users) were frequently noted. Reasons for initiating use varied between the populations (Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eFigure 3. Reason for trying cannabis\u003c/p\u003e \u003cp\u003e Lack of symptom relief from other clinical management was the single most cited motivation for initiation (55.1% clinic, 39.7% EA users). The recommendation to try marijuana was reported to come predominantly from social contacts -- friends, family, or other patients (89.8% clinic, 82.8% EA users). Recommendation of a physician was infrequently reported (12.2% clinic, 20.7% EA users).\u003c/p\u003e \u003cp\u003eThe majority of users reported marijuana to be very or moderately effective for relief of endometriosis/chronic pelvic pain (75.9% clinic, 68.0% EA users). Notably, marijuana was most often considered very effective (53.4% clinic, 39.7% EA users). Routes of administration reported to be most effective were smoked/inhaled (29.2% clinic, 43.1% EA users) and edibles (31.3% clinic, 36.2% EA users). Use by more than one route was reported by 75.7% of users. Among all women who reported using marijuana, those who obtained it directly from a dispensary tended to report greater effectiveness (moderately effective or very effective vs not effective or slightly effective; total sample, p\u0026thinsp;=\u0026thinsp;0.009; clinic, p\u0026thinsp;=\u0026thinsp;0.006; EA, p\u0026thinsp;=\u0026thinsp;0.374 ) However, within the EA group, those who obtained it from friends or family tended to report greater effectiveness (moderately effective or very effective vs not effective or slightly effective; total sample, p\u0026thinsp;=\u0026thinsp;0.097, clinic, p\u0026thinsp;=\u0026thinsp;0.403, EA, p\u0026thinsp;=\u0026thinsp;0.005).\u003c/p\u003e \u003cp\u003eThe most frequently reported side effects of marijuana were comparatively mild. Most users reported experiencing dry mouth (65.9% clinic, 63.5% EA users) and increased appetite (61.0% clinic, 71.2% EA users) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the 54 women who stopped using marijuana, discontinuation was attributed to several reasons (Fig.\u0026nbsp;5).\u003c/p\u003e \u003cp\u003eFigure 5: Reasons for discontinuing cannabis\u003c/p\u003e \u003cp\u003e Collectively, non-clinical factors such as employment or legal risk, social stigma, or obstacles to access were most commonly cited. Lack of effectiveness for symptom control was cited by 42.9% of clinic past users and 30.4% of EA past users. Unpleasant side effects were cited by 23.8% of clinic past users and 26.1% of EA past users. The majority of past users 64.8%) attributed discontinuation to only non-clinical factors, with neither lack of symptom control nor unpleasant side effects cited.\u003c/p\u003e \u003cp\u003eUse of cannabidiol without THC was reported by 27.8% (67 of 240) EA participants, with half (50%, 34 of 67) reporting CBD to be very or moderately effective. Use was reported by 46.0% of clinic participants (57 of 124), with the majority (64.9%, 37 of 57) reporting CBD to be very or moderately effective. CBD was most likely to be reported as moderately effective (31.4% of EA participants, 36.8% of clinic participants). Of the 127 patients reporting cannabidiol use, 99 (78%) also reported marijuana use.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMarijuana use for self-management of endometriosis pain was more common among younger survey participants and in states with less legal restrictions to access; this finding corroborates those of earlier surveys and suggests that prevalence of use may continue to increase with broader decriminalization of marijuana and as a result of generational differences in attitudes towards marijuana. Illegal use of marijuana is common, reported by 52.3% of current users within a state where only medicinal use is legal \u0026ndash; but this is lower than 80% of users reported in a previous Florida-based survey \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTwo predominant patterns of marijuana use were reported: as a rescue pain medication for use once per month, which may represent a strategy for dealing with pain associated with menses or other painful flares \u0026ndash; alternatively as a continuous medication used daily and multiple times per day. Future interventional clinical studies may benefit from focusing on the first pattern of use, as risks from marijuana use would likely be anticipated to be less when used sparingly. Beyond management of pelvic pain, users indicated improved mood and sleep as addition symptoms treated with marijuana, so future interventional studies could include these as secondary outcomes.\u003c/p\u003e \u003cp\u003eDissatisfaction with symptom relief from other therapies was the most cited reason for initiating marijuana, highlighting patients\u0026rsquo; experience of inadequacy of current therapies for management of endometriosis and chronic pelvic pain: for these patients, marijuana was being used to treat chronic refractory pelvic pain. Initiation of marijuana is predominantly due to advisement by lay person social networks outside of the medical establishment.\u003c/p\u003e \u003cp\u003eDiscontinuation of marijuana use was reported by approximately half of users, despite most reporting effective relief of their pelvic pain symptoms with marijuana. While a minority of past users discontinued marijuana due to clinical factors of poor symptom relief or unpleasant side effects, the majority of past users exclusively cited non-clinical reasons for discontinuation: loss of access, social taboo, legal/employment risk. This result mirrors findings from our multivariate analysis that legal access to marijuana is the factor most associated with increased marijuana use. Together, these results identify social and legal factors as likely determinants of use by women with endometriosis and pelvic pain. Our findings reflect those of an international survey of 1,179 endometriosis patients, which identified legality, access, and employment concerns as reasons for discontinuation of marijuana, with a higher proportion of survey respondents reporting marijuana use from countries with legal access. A similar trend was noted elsewhere as a result of legalization of recreational marijuana in Canada (through retrospective chart review, a change from 13.3% users prior to legalization, to 21.5% users after legalization)\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eLow participation is a limitation of our survey, making the data vulnerable to response bias if those who did or did not use marijuana were less likely to participate; estimates of prevalence of marijuana use should be interpreted considering this caution. However, it seems less likely that participation would be influenced by both use and reasons for use, or use and consequences of use. The factors found by this study to be associated with use are therefore unlikely to be spurious consequences of response bias. Because the total number of marijuana users was large, results are unlikely to represent random error.\u003c/p\u003e \u003cp\u003eConcern about legal risk and social taboo likely contributed to low participation and to missing data, especially among the EA group; the clinic group may have had somewhat higher participation due to familiarity with and trust in the researchers and sponsoring institution.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAdditional limitations are that the survey questionnaire was not validated, and that the diagnosis of endometriosis was not based on pathology confirmation. In the EA group the endometriosis diagnosis was self-reported, and in the clinic group the diagnosis may have been made clinically, without surgical confirmation. Although it seems unlikely that significant numbers of women without endometriosis would have been included, a small proportion of participants may have reported on their experience with a less specific cause of pelvic pain.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEndometriosis is a common, incurable cause of chronic pelvic pain in women and many patients report dissatisfaction with available treatment options. Marijuana represents a unique and reportedly effective option for symptom management, but access is variable and limited by social and legal factors. Prevalence of marijuana use among endometriosis patients appears to be most determined by legal and social rather than clinical factors, with discontinuation common despite reported effectiveness.\u003c/p\u003e \u003cp\u003eWithin the changing legal climate across the United States, our data suggest that the number of women who will try marijuana for management of endometriosis and pelvic pain is likely to increase in the future. Variability in legal access to this potentially beneficial treatment option contributes to inequities in chronic pain symptom relief among the diverse population of individuals affected by endometriosis.\u003c/p\u003e \u003cp\u003eIn choosing to study the use of cannabis within a population containing young women and individuals with reproductive capacity, we recognize and do not seek to obscure the potential harms of cannabis use, including the unique morbidity associated with prenatal use of cannabis. We also recognize the vulnerability of this population and the significant lifelong morbidity resulting from chronic, largely refractory pain that develops in the second or third decade of life. For a population whose care may be colored by bias related to fertility capacity and goals, we sought to objectively evaluate and present data on use of cannabis. Our data indicate a history of a sterilizing procedure among one third of cannabis users, and use within pregnancy was rare.\u003c/p\u003e \u003cp\u003eResults of this observational study may inform future interventional studies in which use of marijuana products to alleviate chronic pelvic pain symptoms in women with endometriosis could be assessed in a far more controlled fashion. Future research including interventional trials could seek to minimize variability in marijuana strain, route, dose, and frequency of use, to better ascertain the relationship of these factors to effectiveness of symptom relief and adverse side effects.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEA - Endometriosis Association\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eAcknowledgements: Endometriosis Association, Dignity Health St. Joseph\u0026apos;s Minimally Invasive Gynecologic Surgery Fellowship\u003c/p\u003e\n\u003cp\u003e- Ethical Approval and Consent to participate\u003c/p\u003e\n\u003cp\u003eIRB approval obtained 12/17/2018, #PHX-18-500-169-73-21, St Joseph\u0026rsquo;s Hospital and Medical Center, Institutional Review Board Panel A, 350 W Thomas Rd, Phoenix, AZ 85013\u003c/p\u003e\n\u003cp\u003e- Funding\u003c/p\u003e\n\u003cp\u003eFinancial support for survey dissemination by Dignity Health Medical Group, Department of OB/GYN, Advanced Gynecologic Surgery Division\u003c/p\u003e\n\u003cp\u003e- Conflicts of interest/Competing interests\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eData Availability\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, upon reasonable request.\u003c/p\u003e\n\u003cp\u003e- Code availability\u003c/p\u003e\n\u003cp\u003e N/A\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eAuthors\u0026apos; contributions\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAR contributed to conception and design of study, data collection/patient recruitment. All authors contributed to data analysis and interpretation, statistical analysis, and manuscript preparation. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eASRM. Treatment of pelvic pain associated with endometriosis: A committee opinion. \u003cem\u003eFertil Steril\u003c/em\u003e. 2014;101(4):927-935. doi:10.1016/j.fertnstert.2014.02.012\u003c/li\u003e\n\u003cli\u003eEvans S, Villegas V, Dowding C, Druitt M, O\u0026rsquo;Hara R, Mikocka-Walus A. Treatment use and satisfaction in Australian women with endometriosis: a mixed-methods study. \u003cem\u003eIntern Med J\u003c/em\u003e. 2022;52(12):2096-2106. doi:10.1111/imj.15494\u003c/li\u003e\n\u003cli\u003eArmour M, Sinclair J, Chalmers KJ, Smith CA. Self-management strategies amongst Australian women with endometriosis: A national online survey. \u003cem\u003eBMC Complement Altern Med\u003c/em\u003e. 2019;19(1):1-8. doi:10.1186/s12906-019-2431-x\u003c/li\u003e\n\u003cli\u003eResuehr D, Glore DR, Taylor HS, Bruner-Tran KL, Osteen KG. Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). \u003cem\u003eFertil Steril\u003c/em\u003e. 2012;98(4):948-956.e1. doi:10.1016/j.fertnstert.2012.06.009\u003c/li\u003e\n\u003cli\u003eLeconte M, Nicco C, Ng\u0026ocirc; C, et al. Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis. \u003cem\u003eAmerican Journal of Pathology\u003c/em\u003e. 2010;177(6):2963-2970. doi:10.2353/ajpath.2010.100375\u003c/li\u003e\n\u003cli\u003eEscudero-Lara A, Argerich J, Caba\u0026ntilde;ero D, Maldonado R. Disease-modifying effects of natural \u0026Delta;9-tetrahydrocannabinol in endometriosis-associated pain. \u003cem\u003eElife\u003c/em\u003e. 2020;9:1-17. doi:10.7554/eLife.50356\u003c/li\u003e\n\u003cli\u003eDmitrieva N, Nagabukuro H, Resuehr D, et al. Endocannabinoid involvement in endometriosis. \u003cem\u003ePain\u003c/em\u003e. 2010;151(3):703-710. doi:10.1016/j.pain.2010.08.037\u003c/li\u003e\n\u003cli\u003eBouaziz J, Bar On A, Seidman DS, Soriano D. The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. \u003cem\u003eCannabis Cannabinoid Res\u003c/em\u003e. 2017;2(1):72-80. doi:10.1089/can.2016.0035\u003c/li\u003e\n\u003cli\u003eSanchez AM, Vigano P, Mugione A, Panina-bordignon P, Candiani M. The molecular connections between the cannabinoid system and endometriosis. \u003cem\u003eMol Hum Reprod\u003c/em\u003e. 2012;18(12):563-571. doi:10.1093/molehr/gas037\u003c/li\u003e\n\u003cli\u003eLingegowda H, Williams BJ, Spiess KG, et al. Role of the endocannabinoid system in the pathophysiology of endometriosis and therapeutic implications. \u003cem\u003eJ Cannabis Res\u003c/em\u003e. 2022;4(1). doi:10.1186/s42238-022-00163-8\u003c/li\u003e\n\u003cli\u003eSinclair J, Smith CA, Abbott J, Chalmers KJ, Pate DW, Armour M. Cannabis Use, a Self-Management Strategy Among Australian Women With Endometriosis: Results From a National Online Survey. \u003cem\u003eJournal of Obstetrics and Gynaecology Canada\u003c/em\u003e. 2020;42(3):256-261. doi:10.1016/j.jogc.2019.08.033\u003c/li\u003e\n\u003cli\u003eSinclair J, Collett L, Abbott J, Pate DW, Sarris J, Armour M. Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms. \u003cem\u003ePLoS One\u003c/em\u003e. 2021;16(10 October):1-12. doi:10.1371/journal.pone.0258940\u003c/li\u003e\n\u003cli\u003eCarrubba AR, Ebbert JO, Spaulding AC, Destephano D, Destephano CC. Use of Cannabis for Self-Management of Chronic Pelvic Pain. \u003cem\u003eJ Womens Health\u003c/em\u003e. 2021;30(9):1344-1351. doi:10.1089/jwh.2020.8737\u003c/li\u003e\n\u003cli\u003eMistry M, Simpson P, Morris E, et al. Cannabidiol for the Management of Endometriosis and Chronic Pelvic Pain. \u003cem\u003eJ Minim Invasive Gynecol\u003c/em\u003e. 2022;29(2):169-176. doi:10.1016/j.jmig.2021.11.017\u003c/li\u003e\n\u003cli\u003eLiang AL, Gingher EL, Coleman JS. Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review. \u003cem\u003eObstetrics and gynecology\u003c/em\u003e. 2022;139(2):287-296. doi:10.1097/AOG.0000000000004656\u003c/li\u003e\n\u003cli\u003eHarris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support. \u003cem\u003eJ Biomed Inform\u003c/em\u003e. 2009;42(2). doi:10.1016/j.jbi.2008.08.010\u003c/li\u003e\n\u003cli\u003eHarris PA, Taylor R, Minor BL, et al. The REDCap consortium: Building an international community of software platform partners. \u003cem\u003eJ Biomed Inform\u003c/em\u003e. 2019;95. doi:10.1016/j.jbi.2019.103208\u003c/li\u003e\n\u003cli\u003eZhang Z. Model building strategy for logistic regression: Purposeful selection. \u003cem\u003eAnn Transl Med\u003c/em\u003e. 2016;4(6). doi:10.21037/atm.2016.02.15\u003c/li\u003e\n\u003cli\u003eGeoffrion R, Yang EC, Koenig NA, et al. Recreational Cannabis Use Before and After Legalization in Women With Pelvic Pain. \u003cem\u003eObstetrics and gynecology\u003c/em\u003e. 2021;137(1):91-99. doi:10.1097/AOG.0000000000004207\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"analgesia, cannabis, THC, endometriosis, pelvic pain","lastPublishedDoi":"10.21203/rs.3.rs-4536326/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4536326/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLegal access to cannabinoids is increasing, and patients with chronic pelvic pain from endometriosis may explore use of marijuana for symptom management.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA descriptive cross-sectional survey was undertaken using an anonymous online questionnaire to survey women with endometriosis about their experience with marijuana for management of pelvic pain: exploring symptom benefit, characteristics of use, and factors contributing to use and discontinuation. Participants were recruited from an outpatient gynecology clinic using endometriosis ICD-10 diagnostic codes - and from the Endometriosis Association mailing list.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMarijuana use for symptom relief was reported by 78 (32.2%) Endometriosis Association participants, and 58 (46.8%) clinic participants. Within both populations, marijuana was considered very or moderately effective by most users (68.0\u0026ndash;75.9%). Legality of recreational and medicinal marijuana in the state of residence was strongly associated with use (OR 7.13 [95%CI:2.57\u0026ndash;19.8]). Among users specifying current or past use, discontinuation was reported by 45% (54 of 121), and most frequently attributed to non-clinical factors of legal/employment risk and obstacles to marijuana access; 64.8% of former users attributed discontinuation to non-clinical factors only. Lack of symptom relief from other clinical management was the most cited motivation for initiation (55.1% clinic, 39.7% EA users).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMarijuana use is common among women with endometriosis and chronic, refractory pelvic pain. Legality and access appear to impact use and discontinuation. While legal access to marijuana is associated with increased use, marijuana obtained outside of legal routes is also commonly being used for symptom relief.\u003c/p\u003e","manuscriptTitle":"Self-Reported Use and Effectiveness of Marijuana for Pelvic Pain among Women with Endometriosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 17:32:52","doi":"10.21203/rs.3.rs-4536326/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b3d8deda-4e5f-41c3-932d-90b3e9d83e48","owner":[],"postedDate":"July 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-24T05:38:49+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-16 17:32:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4536326","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4536326","identity":"rs-4536326","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}