Pretreatment MRI parameters as predictive biomarkers for short-term clinical response to dienogest in adenomyosis: a retrospective cohort study

Objectives To evaluate whether pretreatment magnetic resonance imaging (MRI) parameters can predict short-term clinical response to dienogest (DNG) in patients with adenomyosis.

This retrospective study included 78 patients with MRI-diagnosed adenomyosis who underwent pelvic MRI before hormonal therapy between October 2018 and July 2025. Quantitative MRI parameters included T2 signal intensity ratios, diffusion-weighted imaging (DWI) signal intensity ratios, normalized apparent diffusion coefficient (ADC), and uterine morphological parameters. Adenomyosis subtypes were classified according to the modified Kishi criteria. Short-term clinical response was assessed primarily 3–6 months after treatment initiation as a composite clinical outcome encompassing symptom improvement (dysmenorrhea, menstrual blood loss, and/or hemoglobin levels) and treatment continuation; patients were classified as responders or non-responders. Predictive analyses were restricted to the DNG cohort because only one patient in the GnRH cohort was a non-responder.

Of the 78 patients, 32 received gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy and 46 received DNG. In the DNG cohort, 30 patients were responders and 16 were non-responders. MRI-based adenomyosis subtype, lesion distribution, and uterine morphological parameters were not significantly associated with response in DNG-treated patients. However, absolute ADC values were significantly higher in responders (1.03 vs. 0.89 × 10⁻3 mm2/s, P = 0.036), as was the ADC signal intensity ratio relative to the endometrium (ADC SIRendo: 0.92 vs. 0.85, P = 0.034). Receiver operating characteristic analysis demonstrated moderate discrimination for both parameters (area under the curve = 0.70). Optimal cut-off values were 0.951 × 10⁻3 mm2/s for ADC and 0.952 for ADC SIRendo.

Quantitative diffusion MRI parameters were associated with short-term clinical response to DNG, whereas conventional morphological features were not. Diffusion-weighted MRI may provide complementary imaging biomarkers for adenomyosis stratification in DNG-treated patients; prospective validation with longer follow-up is warranted. Graphical abstract Access this article We’re sorry, something doesn't seem to be working properly. Please try refreshing the page. If that doesn't work, please contact support so we can address the problem. Similar content being viewed by others Data availability No datasets were generated or analysed during the current study.

Harada T, Taniguchi F, Guo SW, Choi YM, Biberoglu KO, Tsai SS et al (2023) The Asian Society of Endometriosis and adenomyosis guidelines for managing adenomyosis. Reprod Med Biol 22:e12535. https://doi.org/10.1002/rmb2.12535 Lin CW, Ou HT, Wu MH, Yen CF, Taiwan Endometriosis Society Adenomyosis Consensus Group (2025) Expert consensus on the management of adenomyosis: a modified Delphi method approach by the Taiwan endometriosis society. Gynecol Minim Invasive Ther 14:24-32. https://doi.org/10.4103/gmit.GMIT-D-24-00055 Dason ES, Maxim M, Sanders A, Papillon-Smith J, Ng D, Chan C, Sobel M (2023) Guideline No. 437: diagnosis and management of adenomyosis. J Obstet Gynaecol Can 45:417-429.e1. https://doi.org/10.1016/j.jogc.2023.04.008 Matsubara S, Kawaguchi R, Akinishi M, Nagayasu M, Iwai K, Niiro E, Yamada Y, Tanase Y, Kobayashi H (2019) Subtype I (intrinsic) adenomyosis is an independent risk factor for dienogest-related serious unpredictable bleeding in patients with symptomatic adenomyosis. Sci Rep 9:17654. https://doi.org/10.1038/s41598-019-54096-z Han X, Gao X, Wang F, Shang C, Liu Z, Guo H (2023) Heterogeneity of clinical symptoms and therapeutic strategies for different subtypes of adenomyosis: an initial single-center study in China. Int J Gynaecol Obstet 161:775-783. https://doi.org/10.1002/ijgo.14650 Chung YJ, Rha SE, Kim MR, Shin YR (2023) Correlation between MRI features of adenomyosis and clinical presentation. Diagnostics (Basel) 13:2749. https://doi.org/10.3390/diagnostics13172749 Yajima R, Kido A, Kurata Y, Fujimoto K, Nakao KK, Kuwahara R et al (2021) Diffusion-weighted imaging of uterine adenomyosis: correlation with clinical backgrounds and comparison with malignant uterine tumors. J Obstet Gynaecol Res 47:949-960. https://doi.org/10.1111/jog.14621 Yang Q, Zhang LH, Su J, Liu J (2011) The utility of diffusion-weighted MR imaging in differentiation of uterine adenomyosis and leiomyoma. Eur J Radiol 79:e47-e51. https://doi.org/10.1016/j.ejrad.2011.03.026 Jung DC, Kim MD, Oh YT, Won JY, Lee DY (2012) Prediction of early response to uterine arterial embolisation of adenomyosis: value of T2 signal intensity ratio of adenomyosis. Eur Radiol 22:2044-2049. https://doi.org/10.1007/s00330-012-2436-z Kishi Y, Suginami H, Kuramori R, Yabuta M, Suginami R, Taniguchi F (2012) Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification. Am J Obstet Gynecol 207:114.e1-114.e7. https://doi.org/10.1016/j.ajog.2012.06.027 Moawad G, Fruscalzo A, Youssef Y, Kheil M, Tawil T, Nehme J et al (2023) Adenomyosis: an updated review on diagnosis and classification. J Clin Med 12:4828. https://doi.org/10.3390/jcm12144828 Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N (2008) Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril 90:1583-1588. https://doi.org/10.1016/j.fertnstert.2007.08.051 Munro MG, Critchley HOD, Fraser IS, FIGO Menstrual Disorders Committee (2018) The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet 143:393-408. https://doi.org/10.1002/ijgo.12666 Vora Z, Manchanda S, Sharma R, Das CJ, Hari S, Mathur S, Kumar S, Kachhawa G, Khan MA (2021) Normalized apparent diffusion coefficient: a novel paradigm for characterization of endometrial and subendometrial lesions. Br J Radiol 94:20201069. https://doi.org/10.1259/bjr.20201069 Kurban LAS, Metwally H, Abdullah M, Kerban A, Oulhaj A, Alkoteesh JA (2021) Uterine artery embolization of uterine leiomyomas: predictive MRI features of volumetric response. AJR Am J Roentgenol 216:967-974. https://doi.org/10.2214/AJR.20.22906 Valletta R, Corato V, Lombardo F, Avesani G, Negri G, Steinkasserer M, Tagliaferri T, Bonatti M (2024) Leiomyoma or sarcoma? MRI performance in the differential diagnosis of sonographically suspicious uterine masses. Eur J Radiol 170:111217. https://doi.org/10.1016/j.ejrad.2023.111217 Karakas O, Karakas E, Dogan F, Kilicaslan N, Camuzcuoglu A, Incebiyik A, Camuzcuoglu H (2015) Diffusion-weighted MRI in the differential diagnosis of uterine endometrial cavity tumors. Wien Klin Wochenschr 127:266-273. https://doi.org/10.1007/s00508-015-0709-7 Khan KN, Fujishita A, Kitajima M, Masuzaki H, Nakashima M, Kitawaki J (2016) Biological differences between functionalis and basalis endometria in women with and without adenomyosis. Eur J Obstet Gynecol Reprod Biol 203:49-55. https://doi.org/10.1016/j.ejogrb.2016.05.012 Khan KN, Fujishita A, Koshiba A, Kuroboshi H, Mori T, Ogi H, Itoh K, Nakashima M, Kitawaki J (2019) Biological differences between intrinsic and extrinsic adenomyosis with coexisting deep infiltrating endometriosis. Reprod Biomed Online 39:343-353. https://doi.org/10.1016/j.rbmo.2019.03.210 He YL, Ding N, Li Y, Li Z, Xiang Y, Jin ZY, Xue HD (2016) Cyclic changes of the junctional zone on 3 T MRI images in young and middle-aged females during the menstrual cycle. Clin Radiol 71:341-348. https://doi.org/10.1016/j.crad.2015.12.005 Kido A, Fujimoto K, Matsubara N, Kataoka M, Konishi I, Togashi K (2016) A layer of decreased apparent diffusion coefficient at the endometrial-myometrial junction in uterine adenomyosis. Magn Reson Med Sci 15:220-226. https://doi.org/10.2463/mrms.mp.2015-0084 Nakai Y, Maeda E, Kanda T, Ikemura M, Ushiku T, Sasajima Y, Isshiki S, Abe O (2020) Uterine adenomyosis with extensive glandular proliferation: case series of a rare imaging variant. Diagn Interv Radiol 26:153-159. https://doi.org/10.5152/dir.2019.19252 Hiratsuka D, Matsuo M, Ishizawa C, Fukui Y, Hiraoka T, Aikawa S, Izumi G, Harada M, Wada-Hiraike O, Osuga Y, Hirota Y (2025) Prognostic factors of progesterone resistance in symptomatic adenomyosis: impact of lesion localization on treatment outcome of levonorgestrel intrauterine system. BMC Womens Health 25:286. https://doi.org/10.1186/s12905-025-03817-w Yamanaka A, Kimura F, Kishi Y, Takahashi K, Suginami H, Shimizu Y, Murakami T (2014) Progesterone and synthetic progestin, dienogest, induce apoptosis of human primary cultures of adenomyotic stromal cells. Eur J Obstet Gynecol Reprod Biol 179:170-174. https://doi.org/10.1016/j.ejogrb.2014.05.031 Piriyev E, Schiermeier S, Römer T (2025) Hormonal treatment of endometriosis: a narrative review. Pharmaceuticals (Basel) 18:588. https://doi.org/10.3390/ph18040588

We thank Editage (www.editage.com) for English language editing. Author information Authors and Affiliations Contributions Kazuhiko Morikawa, Akira Baba, Shun Kusada, Satoshi Matsushima and Hiroya Ojiri contributed to conceptualization, manuscript writing, and editing. Yohei Ohki, Megumi Shiraishi, Yoshitake Miyamoto, Aya Igarashi, Yumari Kusano and Ayako Kawabata contributed to collecting and compiling patient data. Yuki Hayakawa conducted additional data analysis during manuscript revision. All authors reviewed the manuscript. Corresponding author Ethics declarations Conflict of interest The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Morikawa, K., Baba, A., Kusada, S. et al. Pretreatment MRI parameters as predictive biomarkers for short-term clinical response to dienogest in adenomyosis: a retrospective cohort study. Abdom Radiol (2026). https://doi.org/10.1007/s00261-026-05592-0 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00261-026-05592-0