{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:30:00Z","timestamp":1787135400642,"version":"build-2736575974"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Glob. Women\u2019s Health"],"abstract":"<jats:p>Endometriosis is frequently managed with hormonal suppression that can induce hypoestrogenism during a period when many patients are still accruing peak bone mass. This narrative review summarizes current clinical and mechanistic evidence on bone health in endometriosis and its treatments and discusses a preliminary conceptual framework for risk stratification and monitoring. This review discusses two hypothetical converging pathways: (1) an intrinsic pathway in which chronic systemic inflammation may shift bone remodeling toward resorption (via cytokine-mediated effects on osteoclastogenic and Wnt signaling pathways and oxidative stress), and (2) an iatrogenic pathway in which ovarian suppression, most notably with gonadotropin-releasing hormone agonists\/antagonists and some progestin-based regimens, reduces estrogen exposure and can lead to measurable short-term bone mineral density loss. Available observational data generally do not show clinically meaningful bone mineral density deficits or excess fracture incidence in untreated endometriosis, but treatment-associated bone mineral density loss is well documented; long-term fracture outcomes and bone-quality measures remain insufficiently studied. We compare the skeletal safety signals across commonly used therapies, discuss the role and limitations of add-back therapy, and highlight when baseline evaluation and follow-up assessment (including consideration of trabecular bone score) may be warranted in higher-risk patients.<\/jats:p>","DOI":"10.3389\/fgwh.2026.1895443","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:10:26Z","timestamp":1787134226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endometriosis-associated bone loss: re-evaluating the potential role of systemic inflammation and hypoestrogenic therapies"],"prefix":"10.3389","volume":"7","author":[{"given":"Farzaneh","family":"Motafeghi","sequence":"first","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences","place":["Tehran, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzieh","family":"Saei Ghare Naz","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences","place":["Tehran, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahimeh","family":"Ramezani Tehrani","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences","place":["Tehran, Iran"]},{"name":"Foundation for Research & Education Excellence","place":["Vestavia Hills, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Behboudi-Gandevani","sequence":"additional","affiliation":[{"name":"Faculty of Nursing and Health Sciences, Nord University","place":["Bod\u00f8, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e66128","DOI":"10.7759\/cureus.66128","article-title":"Endometriosis: a comprehensive exploration of inflammatory mechanisms and fertility implications","volume":"16","author":"Rathod","year":"2024","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1016\/j.cell.2021.04.041","article-title":"Endometriosis: etiology, pathobiology, and therapeutic prospects","volume":"184","author":"Saunders","year":"2021","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1613468","DOI":"10.3389\/fgwh.2025.1613468","article-title":"Global burden of endometriosis from 1990 to 2021 and projections to 2050: a comprehensive analysis based on the global burden of disease study 2021","volume":"6","author":"Yu","year":"2025","journal-title":"Front Glob Womens Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis is a chronic systemic disease: clinical challenges and novel innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.3390\/ijms23031376","article-title":"Osteoporosis due to hormone imbalance: an overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover","volume":"23","author":"Cheng","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"902371","DOI":"10.3389\/fgwh.2022.902371","article-title":"Endometriosis is undervalued: a call to action","volume":"3","author":"Ellis","year":"2022","journal-title":"Front Glob Womens Health"},{"key":"B7","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.cytogfr.2003.10.005","article-title":"IL-6, RANKL, TNF-alpha\/IL-1: interrelations in bone resorption pathophysiology","volume":"15","author":"Steeve","year":"2004","journal-title":"Cytokine Growth Factor Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1056\/NEJM199412153312404","article-title":"Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency","volume":"331","author":"Finkelstein","year":"1994","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s00467-004-1465-5","article-title":"The peak bone mass concept: is it still relevant?","volume":"19","author":"Sch\u00f6nau","year":"2004","journal-title":"Pediatr Nephrol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1210\/jcem-72-2-510","article-title":"Bone mineral density of the lumbar spine in endometriosis subjects compared to an age-similar control population","volume":"72","author":"Lane","year":"1991","journal-title":"J Clin Endocrinol Metab"},{"key":"B11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0015-0282(16)56473-5","article-title":"Bone density and endometriosis","volume":"61","author":"Dochi","year":"1994","journal-title":"Fertil Steril"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1016\/j.fertnstert.2006.05.036","article-title":"Long-term fracture risk among women with proven endometriosis","volume":"86","author":"Melton","year":"2006","journal-title":"Fertil Steril"},{"key":"B13","doi-asserted-by":"publisher","first-page":"dgaa306","DOI":"10.1210\/clinem\/dgaa306","article-title":"Osteoporosis in premenopausal women: a clinical narrative review by the ECTS and the IOF","volume":"105","author":"Pepe","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1222129","DOI":"10.3389\/fimmu.2023.1222129","article-title":"The effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis: a review","volume":"14","author":"Xu","year":"2023","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4370","DOI":"10.3390\/ijms22094370","article-title":"The inflammatory role of pro-resolving mediators in endometriosis: an integrative review","volume":"22","author":"De F\u00e1veri","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"479","DOI":"10.5483\/BMBRep.2013.46.10.141","article-title":"The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases","volume":"46","author":"Lee","year":"2013","journal-title":"BMB Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"778078","DOI":"10.3389\/fimmu.2021.778078","article-title":"Macrophage-Osteoclast associations: origin, polarization, and subgroups","volume":"12","author":"Sun","year":"2021","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.3390\/medicina59101752","article-title":"The RANK-RANKL-OPG system: a multifaceted regulator of homeostasis, immunity, and cancer","volume":"59","author":"De Leon-Oliva","year":"2023","journal-title":"Medicina (Kaunas)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1177\/1759720X12466608","article-title":"Wnt signaling in bone formation and its therapeutic potential for bone diseases","volume":"5","author":"Kim","year":"2013","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"B20","doi-asserted-by":"publisher","first-page":"312","DOI":"10.3390\/diagnostics14030312","article-title":"Endometriosis and the role of pro-inflammatory and anti-inflammatory cytokines in pathophysiology: a narrative review of the literature","volume":"14","author":"Oal\u0103","year":"2024","journal-title":"Diagnostics (Basel)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1038\/s41598-017-02705-0","article-title":"An appropriate wnt\/\u03b2-catenin expression level during the remodeling phase is required for improved bone fracture healing in mice","volume":"7","author":"Bao","year":"2017","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s11914-025-00917-2","article-title":"Bridging genomic research disparities in osteoporosis GWAS: insights for diverse populations","volume":"23","author":"Wu","year":"2025","journal-title":"Curr Osteoporos Rep"},{"key":"B23","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s42003-023-04869-0","article-title":"Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis","volume":"6","author":"Medina-Gomez","year":"2023","journal-title":"Commun Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"9863","DOI":"10.1073\/pnas.1018493108","article-title":"A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2","volume":"108","author":"Zhang","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1007\/s00198-011-1728-5","article-title":"Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells","volume":"23","author":"Baniwal","year":"2012","journal-title":"Osteoporos Int"},{"key":"B26","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/nm1538","article-title":"Dickkopf-1 is a master regulator of joint remodeling","volume":"13","author":"Diarra","year":"2007","journal-title":"Nat Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.3892\/mmr.2020.11152","article-title":"TNF-\u03b1 treatment increases DKK1 protein levels in primary osteoblasts via upregulation of DKK1 mRNA levels and downregulation of miR-335-5p","volume":"22","author":"Li","year":"2020","journal-title":"Mol Med Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1383113","DOI":"10.3389\/fimmu.2024.1383113","article-title":"Toll-like receptor-2 induced inflammation causes local bone formation and activates canonical wnt signaling","volume":"15","author":"Henning","year":"2024","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1742-4933-2-14","article-title":"Osteoporosis, inflammation and ageing","volume":"2","author":"Ginaldi","year":"2005","journal-title":"Immun Ageing"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1093\/humrep\/deaf062","article-title":"The phenotypic and genetic association between endometriosis and immunological diseases","volume":"40","author":"Shigesi","year":"2025","journal-title":"Hum Reprod"},{"key":"B31","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41588-023-01323-z","article-title":"The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions","volume":"55","author":"Rahmioglu","year":"2023","journal-title":"Nat Genet"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N Engl J Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/S0015-0282(98)00540-8","article-title":"Genetic influences on endometriosis in an Australian twin sample","volume":"71","author":"Treloar","year":"1999","journal-title":"Fertil Steril"},{"key":"B34","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jmig.2019.10.020","article-title":"Should genetics now be considered the Pre-eminent etiologic factor in endometriosis?","volume":"27","author":"Montgomery","year":"2020","journal-title":"J Minim Invasive Gynecol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ajhg.2017.12.005","article-title":"Life-course genome-wide association study meta-analysis of total body BMD and assessment of age-specific effects","volume":"102","author":"Medina-Gomez","year":"2018","journal-title":"Am J Hum Genet"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1093\/jbmr\/zjae133","article-title":"Genomic structural variations link multiple genes to bone mineral density in a multi-ethnic cohort study: louisiana osteoporosis study","volume":"39","author":"Su","year":"2024","journal-title":"J Bone Miner Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"728563","DOI":"10.3389\/fgene.2021.728563","article-title":"Identification of new genes and loci associated with bone mineral density based on Mendelian randomization","volume":"12","author":"Liu","year":"2021","journal-title":"Front Genet"},{"key":"B38","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ajhg.2017.06.005","article-title":"10 years of GWAS discovery: biology, function, and translation","volume":"101","author":"Visscher","year":"2017","journal-title":"Am J Hum Genet"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1160397","DOI":"10.3389\/fimmu.2023.1160397","article-title":"Identifying shared genetic loci and common risk genes of rheumatoid arthritis associated with three autoimmune diseases based on large-scale cross-trait genome-wide association studies","volume":"14","author":"Wen","year":"2023","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"268","DOI":"10.3390\/genes11030268","article-title":"Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity","volume":"11","author":"Adewuyi","year":"2020","journal-title":"Genes (Basel)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3389\/fendo.2019.00236","article-title":"Updates on osteoimmunology: what\u2019s new on the cross-talk between bone and immune system","volume":"10","author":"Ponzetti","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/s41574-019-0245-z","article-title":"Rethinking mechanisms, diagnosis and management of endometriosis","volume":"15","author":"Chapron","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"hoac009","DOI":"10.1093\/hropen\/hoac009","article-title":"ESHRE Guideline: endometriosis","volume":"2022","author":"Becker","year":"2022","journal-title":"Hum Reprod Open"},{"key":"B44","article-title":"Endometriosis","volume-title":"Endotext","author":"Carpinello","year":"2000"},{"key":"B45","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrendo.2013.179","article-title":"The role of estrogen and androgen receptors in bone health and disease","volume":"9","author":"Manolagas","year":"2013","journal-title":"Nat Rev Endocrinol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.tem.2012.03.008","article-title":"Estrogen and the skeleton","volume":"23","author":"Khosla","year":"2012","journal-title":"Trends Endocrinol Metab"},{"key":"B47","doi-asserted-by":"publisher","first-page":"cd001297","DOI":"10.1002\/14651858.CD001297","article-title":"Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density","volume":"2003","author":"Farmer","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"B48","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13048-015-0131-9","article-title":"Use of aromatase inhibitors in practice of gynecology","volume":"8","author":"Usluogullari","year":"2015","journal-title":"J Ovarian Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"43","DOI":"10.5114\/pm.2016.58773","article-title":"Aromatase inhibitors in the treatment of endometriosis","volume":"15","author":"S\u0142opie\u0144","year":"2016","journal-title":"Prz Menopauzalny"},{"key":"B50","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/1477-7827-9-89","article-title":"Use of aromatase inhibitors to treat endometriosis-related pain symptoms: a systematic review","volume":"9","author":"Ferrero","year":"2011","journal-title":"Reprod Biol Endocrinol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1186\/s40001-025-03800-z","article-title":"The iron\u2013ferroptosis axis in bone homeostasis: a potential complementary pathway for osteoporosis in endometriosis","volume":"31","author":"Motafeghi","year":"2026","journal-title":"Eur J Med Res"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2307388","DOI":"10.1002\/advs.202307388","article-title":"Ferroptosis in osteocytes as a target for protection against postmenopausal osteoporosis","volume":"11","author":"Jiang","year":"2024","journal-title":"Adv Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3892\/br.2023.1715","article-title":"Fructus ligustri lucidi inhibits ferroptosis in ovariectomy-induced osteoporosis in rats via the Nrf2\/HO-1 signaling pathway","volume":"20","author":"Li","year":"2023","journal-title":"Biomed Rep"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1007\/s00198-019-05103-6","article-title":"Bone health in estrogen-free contraception","volume":"30","author":"Hadji","year":"2019","journal-title":"Osteoporos Int"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1097\/01.AOG.0000450758.95422.c8","article-title":"Committee opinion No. 602: depot medroxyprogesterone acetate and bone effects","volume":"123","year":"2014","journal-title":"Obstet Gynecol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.contraception.2009.11.003","article-title":"Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections","volume":"81","author":"Harel","year":"2010","journal-title":"Contraception"},{"key":"B57","doi-asserted-by":"publisher","first-page":"100509","DOI":"10.1016\/j.xagr.2025.100509","article-title":"Bone mineral density changes during use of progestin-only contraceptives: a rapid review of recent evidence","volume":"5","author":"Erhardt-Ohren","year":"2025","journal-title":"AJOG Glob Rep"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1016\/j.fertnstert.2006.05.024","article-title":"Bone mineral density loss and recovery during 48 months in first-time users of depot medroxyprogesterone acetate","volume":"86","author":"Clark","year":"2006","journal-title":"Fertil Steril"},{"key":"B59","first-page":"381","article-title":"Pharmacokinetics of depot medroxyprogesterone acetate contraception","volume":"41","author":"Mishell","year":"1996","journal-title":"J Reprod Med"},{"key":"B60","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1001\/archpedi.159.2.139","article-title":"Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception","volume":"159","author":"Scholes","year":"2005","journal-title":"Arch Pediatr Adolesc Med"},{"key":"B61","author":"Dennerstein","year":"2018"},{"key":"B62","author":"Witczak","year":""},{"key":"B63","doi-asserted-by":"publisher","first-page":"63","DOI":"10.14740\/jcgo519","article-title":"Depot medroxyprogesterone acetate and bone mineral density","volume":"7","author":"Dennerstein","year":"2018","journal-title":"J Clin Gynecol Obstet"},{"key":"B64","doi-asserted-by":"publisher","first-page":"355","DOI":"10.4183\/aeb.2022.355","article-title":"Effect of oral contraceptives on bone mineral density","volume":"18","author":"Ampatzis","year":"2022","journal-title":"Acta Endocrinol (Bucharest)"},{"key":"B65","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ejogrb.2017.03.011","article-title":"Effects of long-term postoperative dienogest use for treatment of endometriosis on bone mineral density","volume":"212","author":"Seo","year":"2017","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/AOG.0000000000006241","article-title":"Effect of medical therapies for endometriosis on bone health: a systematic review and meta-analysis","volume":"148","author":"Desilets","year":"2026","journal-title":"Obstet Gynecol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.jpag.2017.01.014","article-title":"Dienogest 2\u2005mg daily in the treatment of adolescents with clinically suspected endometriosis: the VISanne study to assess safety in ADOlescents","volume":"30","author":"Ebert","year":"2017","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jpag.2007.04.008","article-title":"Bone density in adolescents treated with a GnRH agonist and add-back therapy for endometriosis","volume":"20","author":"Divasta","year":"2007","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1080\/03007995.2020.1744120","article-title":"Use of dienogest in endometriosis: a narrative literature review and expert commentary","volume":"36","author":"Murji","year":"2020","journal-title":"Curr Med Res Opin"},{"key":"B70","doi-asserted-by":"publisher","first-page":"dead093.678","DOI":"10.1093\/humrep\/dead093.678","article-title":"P-320 change of bone mineral density after long-term use of dienogest with calcium and vitamin D supplementation after surgical treatment of endometrioma","volume":"38","author":"Park","year":"2023","journal-title":"Hum Reprod"},{"key":"B71","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/13697130500148875","article-title":"Pharmacology of estrogens and progestogens: influence of different routes of administration","volume":"8","author":"Kuhl","year":"2005","journal-title":"Climacteric"},{"key":"B72","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1210\/er.2012-1008","article-title":"Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects","volume":"34","author":"Stanczyk","year":"2013","journal-title":"Endocr Rev"},{"key":"B73","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1097\/AOG.0000000000000964","article-title":"Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial","volume":"126","author":"DiVasta","year":"2015","journal-title":"Obstet Gynecol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1007\/s00404-016-4184-9","article-title":"Gonadotropin-releasing hormone agonist with add-back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis","volume":"294","author":"Lee","year":"2016","journal-title":"Arch Gynecol Obstet"},{"key":"B75","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/humupd\/dmaa009","article-title":"Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure","volume":"26","author":"Reis","year":"2020","journal-title":"Hum Reprod Update"},{"key":"B76","doi-asserted-by":"publisher","first-page":"935","DOI":"10.3389\/fendo.2019.00935","article-title":"Regulation of inflammation pathways and inflammasome by sex steroid hormones in endometriosis","volume":"10","author":"Garc\u00eda-G\u00f3mez","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1111\/aji.12552","article-title":"Progestin suppressed inflammation and cell viability of tumor necrosis factor-\u03b1-stimulated endometriotic stromal cells","volume":"76","author":"Grandi","year":"2016","journal-title":"Am J Reprod Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00011-015-0909-7","article-title":"Does dienogest influence the inflammatory response of endometriotic cells? A systematic review","volume":"65","author":"Grandi","year":"2016","journal-title":"Inflammation Res"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3390\/biom12091299","article-title":"Progesterone as an anti-inflammatory drug and immunomodulator: new aspects in hormonal regulation of the inflammation","volume":"12","author":"Fedotcheva","year":"2022","journal-title":"Biomolecules"},{"key":"B80","doi-asserted-by":"publisher","first-page":"101452","DOI":"10.1016\/j.jocd.2023.101452","article-title":"Clinical use of trabecular bone score: the 2023 ISCD official positions","volume":"27","author":"Goel","year":"2024","journal-title":"J Clin Densitom"},{"key":"B81","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s00404-016-4085-y","article-title":"Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis","volume":"294","author":"Zheng","year":"2016","journal-title":"Arch Gynecol Obstet"},{"key":"B82","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/0002-9378(92)91706-G","article-title":"Hormone treatment of endometriosis: the estrogenthreshold hypothesis","volume":"166","author":"Barbieri","year":"1992","journal-title":"Am J Obstet Gynecol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"11342","DOI":"10.3390\/ijms222111342","article-title":"GnRH antagonists with or without add-back therapy: a new alternative in the management of endometriosis?","volume":"22","author":"Donnez","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B84","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3109\/13697137.2015.1129166","article-title":"2016 IMS recommendations on women\u2019s midlife health and menopause hormone therapy","volume":"19","author":"Baber","year":"2016","journal-title":"Climacteric"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1210\/jcem.80.6.7775623","article-title":"A comparison of the effects of oral and transdermal estrogen replacement on insulin sensitivity in postmenopausal women","volume":"80","author":"O\u2019Sullivan","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"B86","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1161\/CIRCULATIONAHA.106.642280","article-title":"Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study","volume":"115","author":"Canonico","year":"2007","journal-title":"Circulation"},{"key":"B87","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/s0029-7844(02)01945-2","article-title":"Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up","volume":"99","author":"Surrey","year":"2002","journal-title":"Obstet Gynecol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"2633494120964517","DOI":"10.1177\/2633494120964517","article-title":"Elagolix in the treatment of endometriosis: impact beyond pain symptoms","volume":"14","author":"Archer","year":"2020","journal-title":"Ther Adv Reprod Health"},{"key":"B89","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s40271-019-00394-7","article-title":"Impact of elagolix on workplace and household productivity among women with moderate to severe pain associated with endometriosis: a pooled analysis of two phase III trials","volume":"12","author":"Surrey","year":"2019","journal-title":"Patient-Patient-Centered Outcomes Res"},{"key":"B90","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1097\/AOG.0000000000002675","article-title":"Long-term outcomes of elagolix in women with endometriosis: results from two extension studies","volume":"132","author":"Surrey","year":"2018","journal-title":"Obstet Gynecol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s00404-014-3230-8","article-title":"Clinical efficacy of add-back therapy in treatment of endometriosis: a meta-analysis","volume":"290","author":"Wu","year":"2014","journal-title":"Arch Gynecol Obstet"},{"key":"B92","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1093\/humupd\/dmx011","article-title":"The management of menopause in women with a history of endometriosis: a systematic review","volume":"23","author":"Gemmell","year":"2017","journal-title":"Hum Reprod Update"},{"key":"B93","doi-asserted-by":"publisher","first-page":"100584","DOI":"10.1016\/j.xagr.2025.100584","article-title":"Safety of 48 months of elagolix with add-back therapy for endometriosis-associated pain","volume":"6","author":"Kim","year":"2025","journal-title":"AJOG Glob Rep"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.3389\/fphys.2018.01834","article-title":"Effect of estrogen on musculoskeletal performance and injury risk","volume":"9","author":"Chidi-Ogbolu","year":"2018","journal-title":"Front Physiol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"21","DOI":"10.21037\/gpm-20-31","article-title":"Use of GnRH analogue in the endometriosis recurrence after surgery","volume":"3","author":"D\u2019Alessandro","year":"2020","journal-title":"Gynecol Pelvic Med"},{"key":"B96","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/S0015-0282(00)01537-5","article-title":"Long-term use of gonadotropin-releasing hormone analogs and hormone replacement therapy in the management of endometriosis: a randomized trial with a 6-year follow-up","volume":"74","author":"Pierce","year":"2000","journal-title":"Fertil Steril"},{"key":"B97","first-page":"145","article-title":"Evidence that the loss of bone mass induced by GnRH agonists is not totally recovered","volume-title":"Maturitas","author":"Revilla","year":"1995"},{"key":"B98","article-title":"Assessment and management of traumatic injuries in older adults","volume-title":"StatPearls","author":"Southern","year":"2024"},{"key":"B99","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1097\/AOG.0b013e318283d1a1","article-title":"Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture","volume":"121","author":"Lanza","year":"2013","journal-title":"Obstet Gynecol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1007\/s00198-015-3440-3","article-title":"The national osteoporosis foundation\u2019s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations","volume":"27","author":"Weaver","year":"2016","journal-title":"Osteoporos Int"},{"key":"B101","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1056\/NEJMcp1513724","article-title":"Postmenopausal osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N Engl J Med"},{"key":"B102","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s11914-013-0161-4","article-title":"Evaluation and management of the premenopausal woman with low BMD","volume":"11","author":"Cohen","year":"2013","journal-title":"Curr Osteoporos Rep"},{"key":"B103","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S2213-8587(18)30308-5","article-title":"Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study","volume":"7","author":"Samelson","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/jbmr.3105","article-title":"Bone microarchitecture assessed by HR-pQCT as predictor of fracture risk in postmenopausal women: the OFELY study","volume":"32","author":"Sornay-Rendu","year":"2017","journal-title":"J Bone Miner Res"},{"key":"B105","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/jbmr.2176","article-title":"Trabecular bone score: a noninvasive analytical method based upon the DXA image","volume":"29","author":"Silva","year":"2014","journal-title":"J Bone Miner Res"},{"key":"B106","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.bone.2015.05.016","article-title":"Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice","volume":"78","author":"Harvey","year":"2015","journal-title":"Bone"},{"key":"B107","volume-title":"Osteoporosis: Assessing the Risk of Fragility Fracture","year":"2012"},{"key":"B108","year":"2023"},{"key":"B109","doi-asserted-by":"publisher","first-page":"191967","DOI":"10.1155\/2014\/191967","article-title":"Medical treatments for endometriosis-associated pelvic pain","volume":"2014","author":"Zito","year":"2014","journal-title":"BioMed Res Int"},{"key":"B110","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s11154-021-09666-w","article-title":"Hormonal treatments for endometriosis: the endocrine background","volume":"23","author":"Vannuccini","year":"2022","journal-title":"Rev Endocr Metab Disord"},{"key":"B111","doi-asserted-by":"publisher","first-page":"113940","DOI":"10.1016\/j.ejogrb.2025.113940","article-title":"Norethindrone acetate versus dienogest for pain relief in endometriosis related pain: a randomized controlled trial","volume":"310","author":"Gurbuz","year":"2025","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B112","doi-asserted-by":"publisher","first-page":"8","DOI":"10.21037\/gpm-2020-mtet-03","article-title":"A narrative review of using GnRH analogues to reduce endometriosis recurrence after surgery: a double-edged sword","volume":"4","author":"New","year":"2021","journal-title":"Gynecol Pelvic Med"},{"key":"B113","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00198-010-1501-1","article-title":"Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards","volume":"22","author":"Vasikaran","year":"2011","journal-title":"Osteoporos Int"},{"key":"B114","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/j.1742-1241.1998.tb11620.x","article-title":"Biochemical markers of bone turnover","volume":"52","author":"Rosalki","year":"1998","journal-title":"Int J Clin Pract"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/j.fertnstert.2012.08.053","article-title":"Aromatase inhibitors for the treatment of endometriosis","volume":"98","author":"Pavone","year":"2012","journal-title":"Fertil Steril"},{"key":"B116","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.fertnstert.2014.02.012","volume":"101","year":"2014","journal-title":"Fertil Steril"},{"key":"B117","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1111\/j.1471-0528.2009.02319.x","article-title":"Immediate and delayed add-back hormonal replacement therapy during ultra long GnRH agonist treatment of chronic cyclical pelvic pain","volume":"116","author":"Al-Azemi","year":"2009","journal-title":"Bjog"},{"key":"B118","first-page":"87","volume-title":"Bone Health and Osteoporosis: A Report of the Surgeon General","year":"2004"},{"key":"B119","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1111\/j.0001-6349.2005.00558.x","article-title":"The effect of physical training on bone mineral density in women with endometriosis treated with GnRH analogs: a pilot study","volume":"84","author":"Bergstr\u00f6m","year":"2005","journal-title":"Acta Obstet Gynecol Scand"}],"container-title":["Frontiers in Global Women's Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgwh.2026.1895443\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:10:28Z","timestamp":1787134228000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgwh.2026.1895443\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":119,"alternative-id":["10.3389\/fgwh.2026.1895443"],"URL":"https:\/\/doi.org\/10.3389\/fgwh.2026.1895443","relation":{},"ISSN":["2673-5059"],"issn-type":[{"value":"2673-5059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"article-number":"1895443"}}