The Effect of Melatonin on Endometrial Histology in Patients with Endometrial Proliferative Disorders: A Double-Blind Randomized Clinical Trial

Endometrial hyperplasia represents a spectrum of morphological and biological changes in the endometrial glands and stroma, ranging from an exaggerated physiological state to carcinoma. In recent years, numerous laboratory studies have evaluated the role of melatonin in regulating endometrial cell proliferation. Emerging evidence indicates an inhibitory role of melatonin administration in various gynecological cancers. Therefore, the present study aims to investigate melatonin's effect on the endometrium's histology in patients with endometrial proliferative disorders. This double-blind, randomized clinical trial was conducted at the Al-Zahra Hospital in Tabriz university of medicail scinsses. The patients with complaints of abnormal vaginal bleeding and with diagnosis of endometrial proliferative disorders or non-atypical hyperplasia were included .The patients were randomly assigned to control and intervention group. The control group received 80 mg Megestrol acetate daily, the intervention group received 80 mg Megestrol acetate daily plus 5 mg of melatonin before bedtime for three months. Both groups were homogenized regarding demographic information, including age, gravidity, parity, and body mass index. The patients were followed up for three months, and after completing of treatment, an endometrial biopsy was performed. The endometrial histology was compared between two groups after three months. Out of the 40 enrolled patients in the study, 37 were included in the final analysis. 18 out of 19 patients (94.7%) in the intervention group and 12 out of 18 patients (66.6%) in the control group had normal biopsy results after treatment . This difference was statistically significant (P<0.05). Adding melatonin to progestin for treatment of endometrial hyperplasia can enhance the treatment response in women with this condition and lead to a higher rate of treatment. Similar content being viewed by others Data availability The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Author information Authors and Affiliations Corresponding author Ethics declarations Declarations Ethical Considerations All ethical considerations for observational studies, including the ethical use of documents and scientific evidence in executing this thesis, were adhered to. No disclosures that could jeopardize the intellectual property rights of the participants were present in this study. All patients were fully informed about the study by reviewing and approving the informed consent form, and the patients incurred no additional costs. All aspects of the Helsinki Declaration regarding the findings' conduct, collection, interpretation, and publication were considered. Additionally, the proposal for this study was approved by the Regional Ethics Committee with the code IR.TBZMED.REC.1402.060 registered with the Clinical Trials Center of Iran under the code IRCT20120922010901N10. Conflict of Interests The authors declare no conflict of interest. Trial Registration The study protocol was registered and confirmed in the Iranian Registry of Clinical Trials under the number (IRCT20120922010901N10). Registration date:1402/02/18 , 2023-05-08 URL to registration on the trial registry website: https://irct.behdasht.gov.ir/user/trial/68200/view Date of enrollment of the first subject: 1402/02/18, 2023-05-08 Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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 Salehi, D., Gharebaghi, P.M., Jafari, M. et al. The Effect of Melatonin on Endometrial Histology in Patients with Endometrial Proliferative Disorders: A Double-Blind Randomized Clinical Trial. Indian J Surg Oncol 17, 41–48 (2026). https://doi.org/10.1007/s13193-025-02288-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s13193-025-02288-7