{"paper_id":"f7af5f1e-7a2d-4667-8ee6-cd635cd1c22d","body_text":"Whole-exome sequencing and single-cell technologies are providing unprecedented insights into adenomyosis, uncovering a complex phylogenetic relationship between eutopic and ectopic endometria and identifying prolactin signalling as a possible pathogenic factor. However, these advances contrast with the failure of a clinical trial for a DRD2 agonist, which underscores the formidable translational challenges.\nKey advances\n-\nWhole-exome sequencing unveiled a complex phylogenetic relationship between eutopic and ectopic endometria3.\n-\nSingle-cell RNA sequencing led to the identification of prolactin signalling as a possible pathogenic factor7.\n-\nSuppression of the prolactin signalling pathway is demonstrated to have therapeutic efficacy in a mouse model of adenomyosis7.\n-\nA clinical trial on the use of a vaginal ring containing a dopamine receptor D2 agonist found no evidence for its efficacy, highlighting the challenges in therapeutic translation9.\nThis is a preview of subscription content, access via your institution\nAccess options\nAccess Nature and 54 other Nature Portfolio journals\nGet Nature+, our best-value online-access subscription\n27,99 € / 30 days\ncancel any time\nSubscribe to this journal\nReceive 12 print issues and online access\n176,64 € per year\nonly 14,72 € per issue\nBuy this article\n- Purchase on SpringerLink\n- Instant access to the full article PDF.\n39,95 €\nPrices may be subject to local taxes which are calculated during checkout\nReferences\nGuo, S. W. Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology. Reproduction 164, R101–R121 (2022).\nGuo, S. W. Drug development for adenomyosis based on pathophysiology. J. Obstet. Gynaecol. Res. 51, e16322 (2025).\nSuda, K. et al. Mutation profile and chromosomal abnormality in adenomyosis. Reproduction 170, e250132 (2025).\nYamaguchi, M. et al. Three-dimensional understanding of the morphological complexity of the human uterine endometrium. iScience 24, 102258 (2021).\nKishi, Y. et al. Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification. Am. J. Obstet. Gynecol. 207, 114.e1–114.e7 (2012).\nLi, L. et al. Mutation and methylation profiles of ectopic and eutopic endometrial tissues. J. Pathol. 255, 387–398 (2021).\nWang, R. et al. Single-cell RNA sequencing identifies the prolactin receptor as a therapeutic target in adenomyosis. Signal Transduct. Target Ther. 10, 258 (2025).\nMori, T., Nagasawa, H. & Takahashi, S. The induction of adenomyosis in mice by intrauterine pituitary isografts. Life Sci. 29, 1277–1282 (1981).\nPellicer, A. et al. Quinagolide vaginal ring for reduction of endometriotic lesions: results from the QLARITY trial. Eur. J. Obstet. Gynecol. Reprod. Biol. 310, 113946 (2025).\nAndersson, J. K. et al. Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: a pilot study. Acta Obstet. Gynecol. Scand. 98, 1341–1350 (2019).\nAcknowledgements\nThe author would like to thank G. Benagiano (University of Rome) and K. Khan (Kyoto Prefectural University of Medicine) for their comments on an earlier version of this manuscript.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nCompeting interests\nS.-W.G. has served as a consultant or speaker within the past 12 months to E3A HealthCare, FimmCyte A.G., Maipl, ReproNova and Ziwig. Neither S.-W.G. nor his family members hold issued stock directly or indirectly in any of these companies. S.-W.G. holds non-exercised options in Heranova.\nRights and permissions\nAbout this article\nCite this article\nGuo, SW. Cracking the enigma of adenomyosis: prospects and challenges. Nat Rev Endocrinol 22, 74–75 (2026). https://doi.org/10.1038/s41574-025-01214-9\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1038/s41574-025-01214-9","source_license":"CC0","license_restricted":false}