Effects of melatonin on disease improvement and serum levels of pro-inflammatory cytokines in patients with non-atypical endometrial hyperplasia

ABSTRACT

Background

Endometrial hyperplasia (EH), an abnormal proliferation of the endometrial cells, is considered as one of the most common causes of abnormal uterine bleeding. Previous studies have reported that melatonin plays a fundamental role in disease treatment. This study aimed the comparison of the effects of progesterone, as the most common therapeutic approach, and melatonin with progesterone alone in improvement of non-atypical endometrial hyperplasia (NEH) and changes in pro-inflammatory cytokine levels.

Methods

Study population consisted of 40 patients with NEH. Patients were divided into two groups, including 20 subjects treated with melatonin and progesterone and 20 individuals treated with progesterone alone. The blood and endometrial sampling was performed from participants before and after a three-month treatment. The histological examination was microscopically done. The serum levels of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured using ELISA.

Results

There was no significant difference in the diabetes status and mean age between patients treated with progesterone and melatonin and those treated with progesterone alone. The improvement rate in the EH was significantly higher in individuals treated with progesterone and melatonin than those treated with progesterone alone (p < 0.05). Additionally, the patients treated with progesterone and melatonin showed significant increases inIFN-γ and TNF-αlevels compared to the control group (p < 0.001-P < 0.05).

Conclusion

Melatonin supplementation has a beneficial effect in the treatment of EH due perhaps to enhance the level of IFN-γ and TNF-α.

KEYWORDS:

• Endometrial hyperplasia
• melatonin
• medroxyprogesterone
• tumor necrosis factor-alpha
• interferon-gamma

Abbreviations

Tumor necrosis factor-alpha: TNF-α; Interferon-gamma: IFN-γ; Interferon‐γ‐inducible protein − 10: IP‐10; Enzyme-linked immunosorbent assay: ELISA; standard deviation: SD.

Acknowledgments

The authors would like to thank all individuals who helped with the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Zahra Vahedpoorfard and Neda Aslani carried out some of the experiments and obtained funding for the work. Habibollah Rahimi participated in the design of the experiments and performed statistical analysis. Hossein Motedayyen and Mohsen Masjedi participated in the study design and drafted the manuscript. All authors read and approved the final manuscript.

Availability of data and material

All data generated or analyzed during this study are included in this article. Further data that support the findings of this study can be obtained from the corresponding author upon reasonable request.

Ethics approval and consent to participate

The study was approved by the ethics committee of Kashan University of Medical Sciences (IR.KAUMS.REC.1400.051) and the trial was registered at IRCT20220116053735N1. Informed consent was taken before taking part in the study. The study was ethically conducted in accordance with the Helsinki World Medical Association Declaration. All authors agree to publish the article.

Additional information

Funding

This study was supported by the Kashan University of Medical Sciences [Grant No: 98015].