Efficacy of Organic Selenium Supplementation on Endometrioma Regression and Pain in Women With Endometriosis: A Triple-Blind Randomized Controlled Clinical Trial

Endometriosis is a non-malignant, estrogen-dependent chronic inflammatory disorder that affects 10–15% of women during their reproductive years. Emerging evidence highlights the undeniable role of oxidative stress in the etiopathogenesis of endometriosis. Selenium, a potent antioxidant, is vital for intracellular redox reactions. Recent research has highlighted the potential of antioxidants as therapeutic agents to mitigate oxidative stress and alleviate endometriosis symptoms. Selenium plays a key role in regulating the enzyme glutathione peroxidase (GPx). This study aimed to evaluate the therapeutic efficacy of a yeast-based organic selenium in disease progression and alleviating painful symptoms. This triple-blind randomized controlled clinical trial was executed within 66 women diagnosed with endometriosis in Tabriz, Iran. Participants were required to possess diagnostically verified endometriosis with endometrioma and a dysmenorrhea score of ≥ 16 on the Menstrual Distress Questionnaire (Moos). Using block randomization with block sizes of 4 or 6, participants were assigned (1:1 ratio) to receive either one 200-mcg capsule of organic selenium or an identical placebo along with routine treatment (2 mg of verojest (dienogest) daily for 3 months). Data were collected using socio-demographic and menstrual-obstetric questionnaires, the Moos, and the visual analogue scale (VAS) for pain. After 3 months, participants completed follow-up questionnaires and underwent ultrasonography. Statistical analyses included descriptive and inferential tests (chi-square, independent t-test, ANCOVA, and repeated-measures ANOVA). A p-value of < 0.05 was considered statistically significant. Three months after the intervention, a statistically significant reduction in endometrioma size was observed in the selenium group (from 4.82 to 3.78 cm) compared to placebo (from 4.07 to 5.31 cm) (adjusted mean difference [aMD]: −1.95 cm; 95% CI −2.6 to −1.3; Cohen’s d = –0.86, large effect). Additionally, the selenium group experienced significantly greater reductions in dysmenorrhea scores (aMD −10.94; 95% CI −15.16 to −6.71; Cohen’s d = –1.14, large effect), dyspareunia (aMD −3.21; 95% CI −4.34 to −2.07), dysuria (aMD −1.41; 95% CI −2.12 to −0.69), dyschezia (aMD −2.11; 95% CI −3.22 to −0.99), and non-cyclic pain (aMD −2.73; 95% CI −3.77 to −1.68) over time (at 1, 2, and 3 months post-intervention), compared to placebo. No serious or health-threatening adverse events were reported in either group. Our findings support the hypothesis that organic selenium supplementation may present a promising adjuvant therapy to reduce the size of endometriomas and alleviate various painful symptoms associated with endometriosis, including dysmenorrhea, dyspareunia, dysuria, non-cyclic pain, and dyschezia. ClinicalTrial.gov Identifier: IRCT20110606006709N26. Similar content being viewed by others Data Availability Data will be made available by the corresponding author on request. Abbreviations - MMQD : - Moos Menstrual Distress Questionnaire - VAS : - Visual analogue scale - ROS : - Reactive oxygen species - GPX : - Glutathione peroxidase - TNF-α : - Tumor necrosis factor-alpha - IL-1β : - Interleukin-1 beta - ICP-MS : - Inductively coupled plasma mass spectrometry - RAS : - Random Allocation Software - EFSA : - European Food Safety Authority

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Special thanks and appreciation are extended to the Clinical Research Development Unit et al. – Zahra Hospital, and Therapeutic Center Sheikh Al-Rais and Tabriz University of Medical Sciences for their research consultation and support. Funding This research was funded by the Vice-Chancellor for Research of Tabriz University of Medical Sciences, Iran. The funding center had no role in the study design, data analysis, or writing this paper. Author information Authors and Affiliations Contributions F.T, M.Sh., A.F-Kh. and Kh.H. contributed to the design of the study. FT and MPN contributed to the collection of data. FT., M.Sh. and A.F-Kh. contributed to the implementation and analysis plan. F.T., M.Sh, A.F-Kh., and Kh.H have written the first draft of this manuscript and all authors have critically read the text and contributed with inputs and revisions, and all authors read and approved the final manuscript. All authors reviewed the manuscript. Corresponding authors Ethics declarations Ethics Approval This study was approved by the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1402.570) on December 18, 2023. The trial’s protocol was also registered at the Iranian Registry for Clinical Trials (code: IRCT20110606006709N26) on December 30, 2023. Written informed consent was obtained from the participants or a parent and/or legal guardian (for minors) for study participation before starting data collection. Consent for Publication Not applicable. Competing interests 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. 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 Teihoomaneshfard, F., Hajizadeh, K., Nasirkandy, M.P. et al. Efficacy of Organic Selenium Supplementation on Endometrioma Regression and Pain in Women With Endometriosis: A Triple-Blind Randomized Controlled Clinical Trial. Biol Trace Elem Res 204, 2542–2551 (2026). https://doi.org/10.1007/s12011-025-04837-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s12011-025-04837-1