Cracking the enigma of adenomyosis: prospects and challenges

Sun‐Wei Guo
Nature reviews. Endocrinology · 2025 · vol. 22(2) , pp. 74–75 · doi:10.1038/s41574-025-01214-9 · PMID:41326652 · W4416946815
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-08 ⓘ

Whole-exome and single-cell sequencing reveal complex endometrial relationships and prolactin signaling in adenomyosis, yet clinical translation faces challenges as shown by a failed DRD2 agonist trial.

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This review discusses how whole-exome sequencing and single-cell transcriptomic approaches have advanced understanding of adenomyosis, including reports of a complex phylogenetic relationship between eutopic and ectopic endometrial tissues and the identification of prolactin signalling as a possible pathogenic factor. It further reports that suppressing the prolactin signalling pathway showed therapeutic efficacy in a mouse model of adenomyosis. As a limitation, it emphasizes translational challenges by contrasting these mechanistic and preclinical findings with a clinical trial of a DRD2 agonist vaginal ring that found no evidence for efficacy. This paper is centrally about adenomyosis — it reviews prospects and challenges in its pathogenesis-driven therapeutic development.

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References

Guo, S. W. Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology. Reproduction 164, R101–R121 (2022). Guo, S. W. Drug development for adenomyosis based on pathophysiology. J. Obstet. Gynaecol. Res. 51, e16322 (2025). Suda, K. et al. Mutation profile and chromosomal abnormality in adenomyosis. Reproduction 170, e250132 (2025). Yamaguchi, M. et al. Three-dimensional understanding of the morphological complexity of the human uterine endometrium. iScience 24, 102258 (2021). Kishi, 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). Li, L. et al. Mutation and methylation profiles of ectopic and eutopic endometrial tissues. J. Pathol. 255, 387–398 (2021). Wang, R. et al. Single-cell RNA sequencing identifies the prolactin receptor as a therapeutic target in adenomyosis. Signal Transduct. Target Ther. 10, 258 (2025). Mori, T., Nagasawa, H. & Takahashi, S. The induction of adenomyosis in mice by intrauterine pituitary isografts. Life Sci. 29, 1277–1282 (1981). Pellicer, 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). Andersson, 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).

Acknowledgements

The 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. Author information Authors and Affiliations Corresponding author Ethics declarations Competing interests S.-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. Rights and permissions About this article Cite this article Guo, 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 Published: Version of record: Issue date: DOI: https://doi.org/10.1038/s41574-025-01214-9

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