Efficacy and role of vitamin D (25-OH-D serum) in the treatment of endometriosis: A systematic review
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HIGHLIGHTS
- A frequent gynecological condition that affects 10–15% of women who are fertile is endometriosis, often leading to pelvic damage and infertility, and has been suggested to be treated with vitamin D due to its role in the immune system and reproductive health.
- Vitamin D may help regulate inflammatory responses and reduce the risk of hyperplasia and cancer, with some studies suggesting it could also influence infertility associated with endometriosis.
ABSTRACT
Objective: A vital component of women's reproductive health, vitamin D has also demonstrated promise in the treatment of endometriosis by enhancing plasma levels and controlling immunological responses in chronic inflammation, including endometriosis. This study sought to shed light on the critical role that vitamin D plays in treating chronic pain and infertility related to endometriosis, as well as to offer fresh perspectives on the therapeutic application of vitamin D in reproductive medicine.
Materials and Methods: This systematic review analyzed literature from PubMed, ScienceDirect, ResearchGate, and Google Scholar, screening 1,156 articles and selecting 20 studies for qualitative synthesis. The focus was on the therapeutic role of vitamin D in treating endometriosis. Inclusion criteria included studies published in the last ten years, in English, involving non-pregnant, healthy women, particularly those with chronic pelvic pain or infertility. Accepted study designs included experimental, cohort, longitudinal, case reports, pilot, and observational studies. Exclusion criteria included non-English publications, animal or pregnant subjects, reviews, inaccessible full texts, and studies lacking relevant on vitamin D or endometriosis.
Results: Twenty eligible studies were selected, involving 5346 women and 60 girls aged 12-50 years with or without endometriosis from Iran, the USA, South Korea, Russia, Turkey, Brazil, Poland, Italy, Germany, and Japan. These studies found that many treatments were tried or done to be able to say that endometriosis can be cured in part by vitamin D.
Conclusion: This systematic review demonstrates that women with endometriosis had reduced vitamin D levels, but evidence on supplementation benefits remains inconclusive. Larger, well-designed trials are needed to confirm vitamin D’s role in endometriosis treatment.
Nodler JL, DiVasta AD, Vitonis AF, et al. Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomi-zed, placebo-controlled trial. Am J Clin Nutr. 2020;112(1):229-36. doi: 10.1093/ajcn/nqaa096. PMID: 32453393; PMCID: PMC7326593.
Akyol A, Şimşek M, İlhan R, et al. Efficacies of vitamin D and omega-3 polyunsaturated fatty acids on experimental endometriosis. Taiwan J Obstet Gynecol. 2016;55(6):835-9. doi: 10.1016/j.tjog. 2015.06.018. PMID: 28040129.
Baek JC, Jo JY, Lee SM, et al. Differences in 25-hydroxy vitamin D and vitamin D-binding protein concentrations according to the severity of endometriosis. Clin Exp Reprod Med. 2019;46(3) :125-31. doi: 10.5653/cerm.2018.00416. Epub 2019 Aug 1. PMID: 31370113; PMCID: PMC6736508.
Cho MC, Kim JH, Jung MH, et al. Analysis of vitamin D-binding protein (VDBP) gene poly-morphisms in Korean women with and without endometriosis. Clin Exp Reprod Med. 2019;46(3): 132-9. doi: 10.5653/cerm.2019.00122. Epub 2019 Aug 13. PMID: 31405270; PMCID: PMC6736509.
Nameni F, Ebrahimmosavi M. The effects of vitamin d3 supplementation and simultaneous exercise on aldehyde dehydrogenase gene expres-sion in endometriosis female rats. Gene, Cell and Tissue. 2023;11(1):1-7. doi: 10.5812/gct-138359.
Lopes VM, Lopes JR, Brasileiro JP, et al. Highly prevalence of vitamin D deficiency among Brazilian women of reproductive age. Arch Endocrinol Metab. 2017;61(1):21-7. doi: 10.1590/ 2359-3997000000216. Epub 2016 Oct 10. PMID: 27737331; PMCID: PMC10522115.
Almassinokiani F, Khodaverdi S, Solaymani-Dodaran et al. Effects of vitamin D on endometriosis-related pain: A double-blind Clinical Trial. Med Sci Monit. 2016;22:4960-6. doi: 10.12659/msm.901838. PMID: 27986972; PMCID: PMC5189720.
Szczepańska M, Mostowska A, Wirstlein P, et al. Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility. Mol Med Rep. 2015;12(5): 7109-15. doi: 10.3892/mmr.2015.4309. Epub 2015 Sep 10. PMID: 26398313.
Tabassi Z, Bagheri S, Samimi M, et al. Clinical and Metabolic Response to Vitamin D Supplementation in Endometrial Hyperplasia: a Randomized, Double-Blind, Placebo-Controlled Trial. Horm Cancer. 2017;8(3):185-95. doi: 10.1007/s12672-017-0290-9. Epub 2017 Mar 10. PMID: 28283863; PMCID: PMC10355957.
Yarmolinskaya M, Denisova A, Tkachenko N, et al. Vitamin D significance in pathogenesis of endo-metriosis. Gynecol Endocrinol. 2021;37(sup1):40-3. doi: 10.1080/09513590.2021.2006516. PMID: 34937505.
Aridan DA. Hubungan antara defisiensi vitamin D dengan kadar interleukin 6 pada anak obes [Correlation between vitamin D deficiency and IL-6 level in obese children]. [Dissertation]. Makassar. Universitas Hasanuddin.
Xie B, Liao M, Huang Y, et al. Association between vitamin D and endometriosis among American women: National Health and Nutrition Examination Survey. PLoS One. 2024;19(1): e0296190. doi: 10.1371/journal.pone.0296190. PMID: 38215179; PMCID: PMC10786361.
Najafi Chamgordani S, Esmaeil N, Hashemi M, et al Evaluation of the natural killer cell subsets and their relationship with serum interferon gamma and vitamin D levels in women with stages III and IV endometriosis: A case-control study. Int J Reprod Biomed. 2024;22(7):593-604. doi: 10.18502/ijrm. v22i7.16933. PMID: 39355310; PMCID: PMC1144 1287.
Delbandi AA, Mahmoudi M, Shervin A, et al. 1,25-dihydroxy vitamin D3 modulates endometriosis-related features of human endometriotic stromal cells. Am J Reprod Immunol. 2016;75(4):461-73. doi: 10.1111/aji.12463. Epub 2015 Dec 22. PMID: 26691009.
Sayegh L, Fuleihan Gel-H, Nassar AH. Vitamin D in endometriosis: a causative or confounding factor? Metabolism. 2014;63(1):32-41. doi: 10.1016/j.metabol.2013.09.012. Epub 2013 Oct 14. PMID: 24135500.
Ciavattini A, Serri M, Delli Carpini G, et al. Ovarian endometriosis and vitamin D serum levels. Gynecol Endocrinol. 2017;33(2):164-7. doi: 10.1080/09513590.2016.1239254. Epub 2016 Nov 4. PMID: 27809683.
Miyashita M, Koga K, Izumi G, et al. Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis. J Clin Endocrinol Metab. 2016;101(6):2371-9. doi: 10.1210/jc.2016-1515. Epub 2016 Apr 1. PMID: 27035829.
Denisova AS, Yarmolinskaya MI, Tkachenko NN. Assessment of 25 (OH) D status in patients with genital endometriosis and clinical efficacy of cholecalciferol in the treatment of the disease. Journal of Obstetrics and Women's Diseases. 2021;70(4):125-33. doi: 10.17816/JOWD70796.
Agic A, Xu H, Altgassen C, et al. Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reprod Sci. 2007;14(5):486-97. doi: 10.1177/19337191073 04565. PMID: 17913968.
Mohagheghian Yaghoubi H, Samadi M, Tajik N, et al. Immunomodulatory effects of vitamin D3 on gene expression of MDGF, EGF and PDGFB in endometriosis. Reprod Biomed Online. 2020;41(5): 782-9. doi: 10.1016/j.rbmo.2020.05.013. Epub 2020 May 26. PMID: 32883565.
Pazhohan A, Danaei-Mehrabad S, Mohamad-Rezaeii Z, et al. The modulating effects of vitamin D on the activity of β-catenin in the endometrium of women with endometriosis: a randomized exploratory trial. Gynecol Endocrinol. 2021;37(3): 278-82. doi: 10.1080/09513590.2020.1858780. Epub 2020 Dec 11. PMID: 33305626.
Pazhohan A, Amidi F, Akbari-Asbagh F, et al. Expression and shedding of CD44 in the endometrium of women with endometriosis and modulating effects of vitamin D: A randomized exploratory trial. J Steroid Biochem Mol Biol. 2018;178:150-8. doi: 10.1016/j.jsbmb.2017.12.001. Epub 2017 Dec 9. PMID: 29229305.
Mehdizadehkashi A, Rokhgireh S, Tahermanesh K, et al. The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. Gynecol Endocrinol. 2021;37(7):640-5. doi: 10.1080/09513590.2021.18 78138. Epub 2021 Jan 29. PMID: 33508990.

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