VITAMIN D IN ENDOMETRIOSIS: MECHANISMS AND CLINICAL POTENTIAL – A LITERATURE REVIEW

Julia Kurcińska; Szymon Kurciński; Martyna Kudła; Gabriela Zając; Paweł Czechowicz; Justyna Czechowicz; Mikołaj Antkiewicz; Aleksandra Arczyńska-Antkiewicz; Maria Drozd; Paulina Łobaza; Agata Krawczyk; Natalia Pawełczak; Dorota Kołkowicz; Julia Kociuba; Zuzanna Kruczek

doi:10.31435/ijitss.2(50).2026.5669

Authors

Julia Kurcińska University Clinical Hospital No. 4 in Lublin, Doktora Kazimierza Jaczewskiego 8, 20-954 Lublin, Poland https://orcid.org/0009-0003-4008-4245
Szymon Kurciński 1st Military Clinical Hospital with a Polyclinic SPZOZ in Lublin, al. Racławickie 23, 20-049 Lublin, Poland https://orcid.org/0009-0001-9157-854X
Martyna Kudła University Clinical Hospital No. 4 in Lublin, Doktora Kazimierza Jaczewskiego 8, 20-954 Lublin, Poland https://orcid.org/0009-0007-7465-5199
Gabriela Zając University Hospital in Krakow, Marii Orwid 11, 30-688 Kraków, Poland https://orcid.org/0009-0009-9222-2711
Paweł Czechowicz University Hospital in Krakow, Marii Orwid 11, 30-688 Kraków, Poland https://orcid.org/0009-0008-0143-0404
Justyna Czechowicz Stefan Żeromski Specialist Hospital in Krakow, Osiedle na Skarpie 66, 31-913 Kraków, Poland https://orcid.org/0009-0003-1035-1648
Mikołaj Antkiewicz Ludwik Rydygier Specialist Hospital in Krakow sp. z o.o., Osiedle Złotej Jesieni 1, 31-820 Kraków, Poland https://orcid.org/0009-0000-8735-9339
Aleksandra Arczyńska-Antkiewicz Jagiellonian University Collegium Medicum, Świętej Anny 12, 31-008 Kraków, Poland https://orcid.org/0009-0008-0410-4751
Maria Drozd Ludwik Rydygier Specialist Hospital in Krakow sp. z o.o., Osiedle Złotej Jesieni 1, 31-820 Kraków, Poland https://orcid.org/0009-0001-4246-4095
Paulina Łobaza Medical Center in Łańcut Sp. z o.o., Ignacego Paderewskiego 5, 37-100 Łańcut, Poland https://orcid.org/0009-0003-3566-005X
Agata Krawczyk University Clinical Hospital No. 4 in Lublin, Doktora Kazimierza Jaczewskiego 8, 20-954 Lublin, Poland https://orcid.org/0009-0004-8883-3572
Natalia Pawełczak Health Care Facility of the Ministry of Interior and Administration in Lublin, Granadierów 3, 20-331 Lublin, Poland https://orcid.org/0000-0001-9933-258X
Dorota Kołkowicz Provincial Specialist Hospital in Wrocław, Henryka Michała Kamieńskiego 73A, 51-124 Wrocław, Poland https://orcid.org/0009-0001-3410-4401
Julia Kociuba LUX MED Sp. z o.o., Szturmowa 2, 02-678 Warszawa, Poland https://orcid.org/0009-0001-9030-0108
Zuzanna Kruczek SP ZOZ MSWiA in Rzeszów, Krakowska 16, 35-111 Rzeszów, Poland https://orcid.org/0009-0008-6153-1995

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5669

Keywords:

Endometriosis, Vitamin D, Vitamin D Receptor, Pelvic Pain, Immunomodulation, Inflammation

Abstract

Objectives: Endometriosis is a chronic inflammatory condition affecting approximately 10% of women of reproductive age. Recent studies have highlighted vitamin D as a potential immunomodulator influencing disease progression. This review aims to synthesize current evidence regarding the mechanistic links between vitamin D and endometriosis, the correlation of serum 25(OH)D levels with disease severity, and the clinical efficacy of supplementation.

Methods: A systematic literature search was conducted using PubMed and the Cochrane Library. The analysis included randomized controlled trials (RCTs), observational studies, and molecular research published within the last eight years. A qualitative narrative synthesis was performed to categorize findings into mechanistic, observational, and interventional themes.

Key Findings: Molecular studies demonstrate that vitamin D inhibits endometriotic cell proliferation, inflammation, and angiogenesis by targeting the NF-κB and VEGF pathways. Observational data generally indicate lower serum 25(OH)D levels in women with advanced endometriosis compared to healthy controls. However, clinical supplementation trials yield heterogeneous results; while some RCTs report significant reductions in pelvic pain and inflammatory markers (hs-CRP), others find no statistical superiority over placebo, potentially due to variations in dosage and baseline vitamin D status.

Conclusions: Vitamin D serves as a biologically plausible adjunctive therapy for endometriosis. While not a definitive cure, its safety and anti-inflammatory properties justify its use in managing deficiency. Future research should prioritize personalized supplementation protocols considering genetic polymorphisms of the vitamin D receptor.

References

Marquardt, R. M., Kim, T. H., Shin, J. H., & Jeong, J. W. (2019). Progesterone and estrogen signaling in the endometrium: What goes wrong in endometriosis? International Journal of Molecular Sciences, 20(15), 3822. https://doi.org/10.3390/ijms20153822

Saunders, P. T. K., & Horne, A. W. (2021). Endometriosis: Etiology, pathobiology, and therapeutic prospects. Cell, 184(11), 2807–2824. https://doi.org/10.1016/j.cell.2021.04.041

Tsamantioti, E. S., & Mahdy, H. (2023). Endometriosis. In StatPearls. StatPearls Publishing.

Zondervan, K. T., Becker, C. M., Koga, K., Missmer, S. A., Taylor, R. N., & Viganò, P. (2018). Endometriosis. Nature Reviews Disease Primers, 4(1), Article 9. https://doi.org/10.1038/s41572-018-0008-5

Farhangnia, P., Noormohammadi, M., & Delbandi, A. A. (2024). Vitamin D and reproductive disorders: A comprehensive review with a focus on endometriosis. Reproductive Health, 21(1), Article 61. https://doi.org/10.1186/s12978-024-01797-y

Jennings, B. S., & Hewison, M. (2025). Vitamin D and endometriosis: Is there a mechanistic link? Cell Biochemistry and Function, 43(1), e70037. https://doi.org/10.1002/cbf.70037

Kalaitzopoulos, D. R., Samartzis, N., Daniilidis, A., Leeners, B., Makieva, S., Nirgianakis, K., Dedes, I., Metzler, J. M., Imesch, P., & Lempesis, I. G. (2022). Effects of vitamin D supplementation in endometriosis: A systematic review. Reproductive Biology and Endocrinology, 20(1), Article 176. https://doi.org/10.1186/s12958-022-01051-9

van Tienhoven, X. A., Ruiz de Chávez Gascón, J., Cano-Herrera, G., Sarkis Nehme, J. A., Souroujon Torun, A. A., Bautista Gonzalez, M. F., Esparza Salazar, F., Sierra Brozon, A., Rivera Rosas, E. G., Carbajal Ocampo, D., & Cabrera Carranco, R. (2025). Vitamin D in reproductive health disorders: A narrative review focusing on infertility, endometriosis, and polycystic ovarian syndrome. International Journal of Molecular Sciences, 26(5), 2256. https://doi.org/10.3390/ijms26052256

Kalaitzopoulos, D. R., Lempesis, I. G., Athanasaki, F., Schizas, D., Samartzis, E. P., Kolibianakis, E. M., & Goulis, D. G. (2020). Association between vitamin D and endometriosis: A systematic review. Hormones, 19(2), 109–121. https://doi.org/10.1007/s42000-019-00166-w

AlAshqar, A., Reschke, L., Kirschen, G. W., & Borahay, M. A. (2021). Role of inflammation in benign gynecologic disorders: From pathogenesis to novel therapies. Biology of Reproduction, 105(1), 7–31. https://doi.org/10.1093/biolre/ioab054

Burjiah, A. R., Sa’adi, A., & Widjiati, W. (2022). Vitamin D inhibited endometriosis development in mice model through interleukin-17 modulation. Open Veterinary Journal, 12(6), 956–964. https://doi.org/10.5455/OVJ.2022.v12.i6.23

Ursache, A., Lozneanu, L., Bujor, I. E., Mandici, C. E., Boiculese, L. V., Bausic, A. I. G., Grigore, M., Socolov, D., & Matasariu, D. R. (2024). Vitamin D—the iceberg in endometriosis—review and meta-analysis. Journal of Personalized Medicine, 14(1), 119. https://doi.org/10.3390/jpm14010119

Evangelisti, G., Barra, F., Fichera, M., & Ferrero, S. (2020). Vitamin D and endometriosis: Is there a correlation with disease severity? Clinical and Experimental Reproductive Medicine, 47(3), 233–234. https://doi.org/10.5653/cerm.2019.03342

Xie, B., Liao, M., Huang, Y., Hang, F., Ma, N., Hu, Q., Wang, J., Jin, Y., & Qin, A. (2024). Association between vitamin D and endometriosis among American women: National Health and Nutrition Examination Survey. PLOS ONE, 19(1), e0296190. https://doi.org/10.1371/journal.pone.0296190

Pan, D., Li, P., Dai, X., & Xie, S. (2025). 25-Hydroxyvitamin D and endometriosis: A bidirectional Mendelian randomization study. Reproductive Sciences, 32(3), 693–701. https://doi.org/10.1007/s43032-024-01517-8

Christoforidis, N., Papapanou, M., Michalakis, D., Dimitraki, M., Chatziparasidou, A., & Siristatidis, C. (2025). Effect of vitamin D supplementation on frozen embryo transfer cycle outcomes. Human Fertility, 28(1), 2493251. https://doi.org/10.1080/14647273.2025.2493251

Somigliana, E., Sarais, V., Reschini, M., Ferrari, S., Makieva, S., Cermisoni, G. C., Paffoni, A., Papaleo, E., & Viganò, P. (2021). Single oral dose of vitamin D3 supplementation prior to in vitro fertilization and embryo transfer in normal weight women: The SUNDRO randomized controlled trial. American Journal of Obstetrics and Gynecology, 225(3), 283.e1–283.e10. https://doi.org/10.1016/j.ajog.2021.04.234

Mehdizadehkashi, A., Rokhgireh, S., Tahermanesh, K., Eslahi, N., Minaeian, S., & Samimi, M. (2021). The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. Gynecological Endocrinology, 37(7), 640–645. https://doi.org/10.1080/09513590.2021.1878138

Barnard, N. D., Holtz, D. N., Schmidt, N., Kolipaka, S., Hata, E., Sutton, M., Znayenko-Miller, T., Hazen, N. D., Cobb, C., & Kahleova, H. (2023). Nutrition in the prevention and treatment of endometriosis: A review. Frontiers in Nutrition, 10, 1089891. https://doi.org/10.3389/fnut.2023.1089891

Malvezzi, H., Marengo, E. B., Podgaec, S., & Piccinato, C. A. (2020). Endometriosis: Current challenges in modeling a multifactorial disease of unknown etiology. Journal of Translational Medicine, 18(1), Article 311. https://doi.org/10.1186/s12967-020-02471-0

Buggio, L., Somigliana, E., Pizzi, M. N., Dridi, D., Roncella, E., & Vercellini, P. (2019). 25-Hydroxyvitamin D serum levels and endometriosis: Results of a case-control study. Reproductive Sciences, 26(2), 172–177. https://doi.org/10.1177/1933719118766259

Delbandi, A. A., Torab, M., Abdollahi, E., Khodaverdi, S., Rokhgireh, S., Moradi, Z., Heidari, S., & Mohammadi, T. (2021). Vitamin D deficiency as a risk factor for endometriosis in Iranian women. Journal of Reproductive Immunology, 143, 103266. https://doi.org/10.1016/j.jri.2020.103266

Chen, W. C., Cheng, C. M., Liao, W. T., & Chang, T. C. (2022). Urinary biomarkers for detection of clinical endometriosis or adenomyosis. Biomedicines, 10(4), 833. https://doi.org/10.3390/biomedicines10040833

Cho, M. C., Kim, J. H., Jung, M. H., Cho, I. A., Jo, H. C., Shin, J. K., Lee, S. A., Choi, W. J., & Lee, J. H. (2019). Analysis of vitamin D-binding protein (VDBP) gene polymorphisms in Korean women with and without endometriosis. Clinical and Experimental Reproductive Medicine, 46(3), 132–139. https://doi.org/10.5653/cerm.2019.00122

Jafari, M., Khodaverdi, S., Sadri, M., Moradi, Z., Mohammadi, T., Heidari, S., Akhavan Sales, Z., & Delbandi, A. A. (2021). Association between vitamin D receptor (VDR) and vitamin D binding protein (VDBP) gene polymorphisms and endometriosis susceptibility in Iranian women. Reproductive Sciences, 28(12), 3491–3497. https://doi.org/10.1007/s43032-021-00598-z

Yarmolinskaya, M., Denisova, A., Tkachenko, N., Ivashenko, T., Bespalova, O., Tolibova, G., & Tral, T. (2021). Vitamin D significance in pathogenesis of endometriosis. Gynecological Endocrinology, 37(sup1), 40–43. https://doi.org/10.1080/09513590.2021.2006516