{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:44:22Z","timestamp":1793663062115,"version":"4.5.1"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005716","name":"Babol University of Medical Sciences","doi-asserted-by":"publisher","award":["724134790"],"award-info":[{"award-number":["724134790"]}],"id":[{"id":"10.13039\/501100005716","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec027\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>To evaluate the effect of melatonin supplementation on sleep quality and pelvic pain in infertile women with endometriosis and sleep disturbances.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec028\">\n<jats:title>Materials and analysis<\/jats:title>\n<jats:p>A randomized, triple-blind, placebo-controlled trial was conducted among 80 infertile women with endometriosis and sleep disturbances. Participants were randomly assigned to receive either 5\u2009mg melatonin or placebo for 2 months. The primary outcome was change in overall sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes included changes in specific PSQI domains and chronic pelvic pain.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec029\">\n<jats:title>Result<\/jats:title>\n<jats:p>Among 80 infertile women with endometriosis and sleep disturbances, melatonin significantly improved overall sleep quality compared to placebo, with a large effect size (p &lt; 0.001, \u03b7\u00b2 = 0.20, Cohen\u2019s d=1). The mean difference in sleep quality was a reduction of -1.7 on the PSQI, although it did not reach the clinically meaningful threshold of 3 points. Melatonin also led to considerable improvements in specific PSQI domains including: a substantial increase in sleep duration and a marked reduction in sleep disturbances. Furthermore, melatonin significantly decreased sleep latency, exhibiting a large effect size, and contributed to a medium reduction in the use of sleep medications. However, no significant improvements were noted in sleep efficiency, daytime dysfunction, or subjective sleep quality. Additionally, melatonin significantly reduced chronic pelvic pain, with a large effect size (p &lt; 0.001, \u03b7\u00b2 = 0.18, Cohen\u2019s d = 0.93).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec030\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>While melatonin may improve sleep quality and reduce pelvic pain, further investigation is needed to assess its clinical relevance in this population.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec031\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>ClinicalTrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/IRCT20171209037794N4\" xlink:type=\"simple\">IRCT20171209037794N4<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0321635","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T17:31:21Z","timestamp":1744824681000},"page":"e0321635","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Melatonin and sleep parameters in infertile women with endometriosis: first results from the triple-blind randomized controlled trial of administration of melatonin in chronic pelvic pain and sleep disturbance"],"prefix":"10.1371","volume":"20","author":[{"given":"Sedighe","family":"Esmaeilzadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Habibolahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Moher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Basirat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemat","family":"Gholinia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Golsorkhtabaramiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8077-3569","authenticated-orcid":true,"given":"Parvaneh","family":"Mirabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"issue":"9","key":"pone.0321635.ref001","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1089\/jwh.2019.8008","article-title":"A Quantitative Analysis of Sleep Quality in Women with Endometriosis","volume":"29","author":"K Arion","year":"2020","journal-title":"J Womens Health (Larchmt)"},{"key":"pone.0321635.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12905-020-01036-z","article-title":"Effects of endometriosis on sleep quality of women: does life style factor make a difference","volume":"20","author":"S Youseflu","year":"2020","journal-title":"BMC women\u2019s health"},{"issue":"1","key":"pone.0321635.ref003","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/ejp.514","article-title":"Pain threshold and sleep quality in women with endometriosis","volume":"19","author":"FR Nunes","year":"2015","journal-title":"Eur J Pain"},{"issue":"7","key":"pone.0321635.ref004","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/humrep\/dez082","article-title":"Melatonin activity and receptor expression in endometrial tissue and endometriosis","volume":"34","author":"AA Mosher","year":"2019","journal-title":"Hum Reprod"},{"key":"pone.0321635.ref005","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejogrb.2015.11.026","article-title":"Symptomatic endometriosis of the posterior cul-de-sac is associated with impaired sleep quality, excessive daytime sleepiness and insomnia: a case-control study","volume":"209","author":"U Leone Roberti Maggiore","year":"2017","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"8","key":"pone.0321635.ref006","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1093\/humrep\/dey115","article-title":"Fatigue - a symptom in endometriosis","volume":"33","author":"A Ramin-Wright","year":"2018","journal-title":"Hum Reprod"},{"key":"pone.0321635.ref007","article-title":"The relationship between sleep disturbances and endometriosis: A systematic review","author":"C Sumbodo","year":"2023","journal-title":"European Journal of Obstetrics & Gynecology and Reproductive Biology"},{"issue":"1","key":"pone.0321635.ref008","doi-asserted-by":"crossref","first-page":"e12842","DOI":"10.1111\/jpi.12842","article-title":"Melatonin inhibits endometriosis development by disrupting mitochondrial function and regulating tiRNAs","volume":"74","author":"S Park","year":"2023","journal-title":"J Pineal Res"},{"issue":"1","key":"pone.0321635.ref009","doi-asserted-by":"crossref","first-page":"119-28.e1-5","DOI":"10.1016\/j.fertnstert.2015.09.003","article-title":"Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis","volume":"105","author":"JM Wessels","year":"2016","journal-title":"Fertil Steril"},{"key":"pone.0321635.ref010","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2147\/JPR.S228577","article-title":"Role of Melatonin in the Regulation of Pain","volume":"13","author":"S Xie","year":"2020","journal-title":"J Pain Res"},{"issue":"6","key":"pone.0321635.ref011","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.pain.2013.02.025","article-title":"Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial","volume":"154","author":"A Schwertner","year":"2013","journal-title":"Pain"},{"issue":"59","key":"pone.0321635.ref012","doi-asserted-by":"crossref","first-page":"100582","DOI":"10.18632\/oncotarget.21504","article-title":"Exogenous melatonin in the treatment of pain: a systematic review and meta-analysis","volume":"8","author":"C Zhu","year":"2017","journal-title":"Oncotarget"},{"issue":"18","key":"pone.0321635.ref013","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.3390\/jcm10184040","article-title":"Insomnia Symptoms and Chronic Pain among Patients Participating in a Pain Rehabilitation Program-A Registry Study","volume":"10","author":"J Lind","year":"2021","journal-title":"J Clin Med"},{"issue":"8","key":"pone.0321635.ref014","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.5664\/jcsm.8464","article-title":"The relationship between insomnia and endometriosis","volume":"16","author":"IA Ishikura","year":"2020","journal-title":"J Clin Sleep Med"},{"issue":"1","key":"pone.0321635.ref015","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41386-019-0439-z","article-title":"Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications","volume":"45","author":"M Haack","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"pone.0321635.ref016","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.sleep.2020.10.018","article-title":"Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial","volume":"76","author":"H Xu","year":"2020","journal-title":"Sleep Med"},{"issue":"1","key":"pone.0321635.ref017","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12957-023-02895-0","article-title":"Improvement of sleep quality in isolated metastatic patients with spinal cord compression after surgery","volume":"21","author":"S Cao","year":"2023","journal-title":"World J Surg Oncol"},{"issue":"1","key":"pone.0321635.ref018","article-title":"Health-related quality of life (Nottingham Health Profile) in patients with endometriomas: correlation with clinical variables and self-reported limitations","volume":"15","author":"K Chmaj-Wierzchowska","year":"2020","journal-title":"Archives of Medical Science"},{"issue":"2","key":"pone.0321635.ref019","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3390\/ijerph18020460","article-title":"Sleep Quality, Mental and Physical Health: A Differential Relationship","volume":"18","author":"V Clement-Carbonell","year":"2021","journal-title":"Int J Environ Res Public Health"},{"issue":"2","key":"pone.0321635.ref020","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ogc.2022.02.006","article-title":"Approach to Diagnosis and Management of Chronic Pelvic Pain in Women: Incorporating Chronic Overlapping Pain Conditions in Assessment and Management","volume":"49","author":"SR Till","year":"2022","journal-title":"Obstet Gynecol Clin North Am"},{"issue":"7","key":"pone.0321635.ref021","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1016\/j.jmig.2019.09.750","article-title":"Assessing Pain and Sleep Patterns in Endometriosis: A Pilot Study Using Passive Radio Sensors","volume":"26","author":"M Loring","year":"2019","journal-title":"Journal of Minimally Invasive Gynecology"},{"key":"pone.0321635.ref022","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.smrv.2017.08.001","article-title":"Effects of sleep changes on pain-related health outcomes in the general population: A systematic review of longitudinal studies with exploratory meta-analysis","volume":"39","author":"EF Afolalu","year":"2018","journal-title":"Sleep Med Rev"},{"issue":"10","key":"pone.0321635.ref023","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1007\/s00192-023-05560-y","article-title":"Impact of chronic pelvic pain and painful bladder syndrome on the Pittsburgh Sleep Quality Index on women with deep endometriosis: a cross-sectional study","volume":"34","author":"RJ de Souza","year":"2023","journal-title":"Int Urogynecol J"},{"issue":"3","key":"pone.0321635.ref024","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jpainsymman.2012.08.019","article-title":"Analgesic and sedative effects of melatonin in temporomandibular disorders: a double-blind, randomized, parallel-group, placebo-controlled study","volume":"46","author":"LP Vidor","year":"2013","journal-title":"J Pain Symptom Manage"},{"issue":"19","key":"pone.0321635.ref025","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.3390\/nu14194087","article-title":"Melatonin in Endometriosis: Mechanistic Understanding and Clinical Insight","volume":"14","author":"Y Li","year":"2022","journal-title":"Nutrients"},{"issue":"6","key":"pone.0321635.ref026","doi-asserted-by":"crossref","first-page":"e0286182","DOI":"10.1371\/journal.pone.0286182","article-title":"Adjuvant use of melatonin for pain management in endometriosis-associated pelvic pain-A randomized double-blinded, placebo-controlled trial","volume":"18","author":"L S\u00f6derman","year":"2023","journal-title":"PLoS One"},{"issue":"1","key":"pone.0321635.ref027","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jpain.2008.08.007","article-title":"Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study","volume":"10","author":"W Caumo","year":"2009","journal-title":"J Pain"},{"issue":"4","key":"pone.0321635.ref028","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.bja.2024.01.012","article-title":"Melatonin treatment has consistent but transient beneficial effects on sleep measures and pain in patients with severe chronic pain: the DREAM-CP randomised controlled trial","volume":"132","author":"UM Onyeakazi","year":"2024","journal-title":"Br J Anaesth"},{"issue":"3","key":"pone.0321635.ref029","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jfma.2022.10.001","article-title":"The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials","volume":"122","author":"K-H Chen","year":"2023","journal-title":"J Formos Med Assoc"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T17:31:29Z","timestamp":1744824689000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321635"}},"subtitle":[],"editor":[{"given":"Marcello","family":"Iriti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0321635","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,16]]}}}