Therapeutic and prophylactic effects of vitamin D in gynecological diseases associated with excessive proliferation

Kuznetsova I.V.

I.M. Sechenov First Moscow State Medical University, Moscow 119992, Malaya Trubetskaya str. 8, bld. 2, Russia
Objective. To carry out a systems analysis of the data available in the current literature on the impact of vitamin D deficiency on the risk of endometriosis and reproductive cancer, as well as on the possibilities of vitamin D supplementation in order to treat and prevent these diseases.
Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic.
Results. The paper describes the mechanisms by which vitamin D is involved in the processes of inflammation, immunomodulation, and proliferation, as well as the role of its deficiency in pathogenesis of pathological proliferation and inflammation in endometriosis, breast cancer, and ovarian cancer. It gives the data of clinical trials confirming the role of vitamin D deficiency in the progression and negative effects of endometriosis and carcinogenesis, the possibility of vitamin D supplementation for the prevention and adjunct therapy of reproductive cancer and endometriosis.
Conclusion. It is necessary to conduct further studies to experimentally and clinically evaluate vitamin D deficiency in endometriosis and cancer. Currently, vitamin D supplements should be prescribed to patients with this pathology if they have been found to have a low blood level of 25(OH)D3.


vitamin D
breast cancer
ovarian cancer


1. Lucisano S., Buemi M., Passantino A., Aloisi C., Cernaro V., Santoro D. New insights on the role of vitamin D in the progression of renal damage. Kidney Blood Press. Res. 2013; 37(6): 667-78.

2. Savica V., Bellinghieri G., Monardo P., Muraca U., Santoro D. An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts. J. Nephrol. 2013;26(3): 456-64.

3. Holick M.F., Chen T.C. Vitamin D deficiency: a world- wide problem with health consequences. Am. J. Clin. Nutr. 2008; 87(4): 1080S-6S.

4. Шелепова Е.С., Зазерская И.Е., Хазова Е.Л., Кузнецова Л.В., Яковлева Н.Ю., Васильева Е.Ю. Особенности обмена кальция при беременности в зависимости от насыщенности организма витамином D. Гинекология. 2016; 18(2): 8-10. [Shelepova E.S., Zazerskiy I.E., Khazova E.L., Kuznetsova L.V., Yakovleva N.Yu., Vasilieva E.Y. Features of calcium metabolism during pregnancy, depending on the saturation of the organism with vitamin D. Ginekologiya. 2016; 18(2): 8-10. (in Russian)]

5. Santoro D., Caccamo D., Gagliostro G., Ientile R., Benvenga S., Bellinghieri G., Savica V. Vitamin D metabolism and activity as well as genetic variants of the vitamin D receptor (VDR) in chronic kidney disease patients. J. Nephrol. 2013; 26(4): 636-44.

6. Kim S.Y. The pleiomorphic actions of vitamin D and its importance for children. Ann. Pediatr. Endocrinol. Metab. 2013; 18(2): 45-54.

7. Vuolo L., di Somma C., Faggiano A., Colao A. Vitamin D and cancer. Front. Endocrinol. (Lausanne). 2012; 3: 58.

8. Sturlese E., Salmeri F.M., Retto G., Pizzo A., De Dominici R., Ardita F.V. et al. Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. J. Reprod. Immunol. 2011;92(1-2): 74-81.

9. van Etten E., Stoffels K., Gysemans C., Mathieu C., Overbergh L. Regulation of vitamin D homeostasis: implications for the immune system. Nutr. Rev. 2008; 66(10): S125-34.

10. Borkowski J., Gmyrek G.B., Madej J.P., Nowacki W., Goluda M., Gabryś M. et al. Serum and peritoneal evaluation of vitamin D-binding protein in women with endometriosis. Postepy Hig. Med. Dosw. (Online). 2008; 62: 103-9.

11. Harris H.R., Chavarro J.E., Malspeis S., Willett W.C., Missmer S.A. Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am. J. Epidemiol. 2013; 177(5): 420-30.

12. Ciavattini A., Serri M., Delli Carpini G., Morini S., Clemente N. Ovarian endometriosis and vitamin D serum levels. Gynecol. Endocrinol. 2017; 33(2): 164-7.

13. Sayegh L., Fuleihan G.E.H., Nassar A.H. Vitamin D in endometriosis: a causative or confounding factor? Metabolism. 2014; 63(1): 32-41.

14. Vilarino F.L., Bianco B., Lerner T.G., Teles J.S., Mafra F.A., Christofolini D.M., Barbosa C.P. Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis. Hum. Immunol. 2011; 72(4): 359-63.

15. Faserl K., Golderer G., Kremser L., Lindner H., Sarg B., Wildt L., Seeber B. Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis. J. Clin. Endocrinol. Metab. 2011; 96(1):E233-41.

16. Cho S., Choi Y.S., Yim S.Y., Yang H.I., Jeon Y.E., Lee K.E. et al. Urinary vitamin D-binding protein is elevated in patients with endometriosis. Hum. Reprod. 2012; 27(2): 515-22.

17. Fassbender A., Burney R.O., O D.F., D’Hooghe T., Giudice L. Update on biomarkers for the detection of endometriosis. Biomed. Res. Int. 2015; 2015: 130854.

18. Di Rosa M., Malaguarnera G., De Gregorio C., Palumbo M., Nunnari G., Malaguarnera L. Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell. Immunol. 2012; 280(1): 36-43.

19. Zelenko Z., Aghajanova L., Irwin J.C., Giudice L.C. Nuclear receptor, coregulator signaling, and chromatin remodeling pathways suggest involvement of the epigenome in the steroid hormone response of endometrium and abnormalities in endometriosis. Reprod. Sci. 2012; 19(2): 152-62.

20. Yildirim B., Guler T., Akbulut M., Oztekin O., Sariiz G. 1-alpha,25-dihydroxyvitamin D3 regresses endometriotic implants in rats by inhibiting neovascularization and altering regulation of matrix metalloproteinase. Postgrad. Med. 2014; 126(1): 104-10.

21. Krishnan A.V., Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Ann. Rev. Pharmacol. Toxicol. 2011; 51: 311-36.

22. Miyashita M., Koga K., Izumi G., Sue F., Makabe T., Taguchi A. et al. Effects of 1,25-dihydroxy vitamin D3 on endometriosis. J. Clin. Endocrinol. Metab. 2016; 101(6): 2371-9.

23. Mariani M., Viganò P., Gentilini D., Camisa B., Caporizzo E., Di Lucia P. et al. The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis development in a mouse model by inhibiting peritoneal inflammation. Hum. Reprod. 2012; 27(7): 2010-9.

24. Lasco A., Catalano A., Benvenga S. Improvement of primary dysmenorrhea caused by a single oral dose of vitamin D: results of a randomized, double-blind, placebo-controlled study. Arch. Intern. Med. 2012; 172(4): 366-7.

25. Almassinokiani F., Khodaverdi S., Solaymani-Dodaran M., Akbari P., Pazouki A. Effects of vitamin D on endometriosis-related pain: a double-blind clinical trial. Med. Sci. Monit. 2016; 22: 4960-6.

26. Mormile R., Vittori G. Vitamin D intake and endometriosis: The good and the bad. Eur. J. Obstet. Gynecol. Reprod. Biol. 2014; 177: 152-3.

27. Touvier M., Chan D.S., Lau R., Aune D., Vieira R., Greenwood D.C. et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiol. Biomarkers Prev. 2011; 20(5): 1003-16.

28. Chen P., Hu P., Xie D., Qin Y., Wang F., Wang H. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res. Treat. 2010; 121(2): 469-77.

29. Chung M., Lee J., Terasawa T., Lau J., Trikalinos T.A. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. preventive services task force. Ann. Intern. Med. 2011; 155(12): 827-38.

30. Liu S.L., Zhao Y.P., Dai M.H., You L., Wen Z., Xu J.W. Vitamin D status and the risk of pancreatic cancer: a meta-analysis. Chin. Med. J.(Engl.). 2013; 126(17): 3356-9.

31. Shanmugalingam T., Crawley D., Bosco C., Melvin J., Rohrmann S., Chowdhury S. et al. Obesity and cancer: the role of vitamin D. BMC Cancer. 2014; 14: 712.

32. Colston W. Vitamin D and breast cancer risk. Best Pract. Res. Clin. Endocrinol. Metab. 2008; 22(4): 587-99.

33. Almquist M., Bondeson A.G., Bondeson L., Malm J., Banjer J. Serum levels of vitamin D, PTH and calcium and breast cancer risk - a prospective nested case-control study. Int. J. Cancer. 2010; 127(9): 2159-68.

34. Shao T., Klein P., Grossbarda M.L. Vitamin D and breast cancer. Oncologist. 2012; 17(1): 36-45.

35. Amir E., Cecchini R.S., Ganz P.A., Costantino J.P., Beddows S., Hood N., Goodwin P.J. 25-Hydroxyvitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1. Breast Cancer Res. Treat. 2012; 133(3): 1077-88.

36. Bauer S.R., Hankinson S.E., Bertone-Johnson E.R., Ding E.L. Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies. Medicine(Baltimore). 2013;92(3): 123-31.

37. Bolland M.J., Grey A., Gamble G.D., Reid I.R. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am. J. Clin. Nutr. 2011;94(4): 1144-9.

38. Avenell A., MacLennan G.S., Jenkinson D.J., McPherson G.C., McDonald A.M., Pant P.R. et al. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D and/ or calcium (RECORD Trial). J. Clin. Endocrino.l Metab. 2012; 97(2): 614-22.

39. Zheng Y., Zhu J., Zhou M., Cui L., Yao W., Liu Y. Meta-analysis of long-term vitamin D supplementation on overall mortality. PLoS One. 2013: 8(12): e82109.

40. Rose A.A., Elser C., Ennis M., Goodwin P.J. Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis. Breast Cancer Res. Treat. 2013; 141(3): 331-9.

Received 16.02.2018

Accepted 02.03.2018

About the Authors

Irina Vsevolodovna Kuznetsova, MD, professor of the Department of Obstetrics and Gynecology No. 1, Therapeutic Faculty, I.M. Sechenov First Moscow State Medical University. 119992, Russia, Moscow, Malaya Trubetskaya str. 8, bld. 2

For citations: Kuznetsova I.V. Therapeutic and prophylactic effects of vitamin D in gynecological diseases associated with excessive proliferation. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (4): 138-43. (in Russian)

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.