Table of contents
- Growth of Uterine Fibroids halted by 50,000 IU of Vitamin D weekly – RCT April 2021
- All Uterine Fibroid studies found an inverse association with low vitamin D (helped by 4 of 5 interventions) – Review Aug 2022
- Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation -Nov 2020
- Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids - Feb 2021
- Uterine Fibroid Recurrence cut in half by 1,000 IU of vitamin D daily - pilot RCT Feb 2022
- VitaminDWiki pages with FIBROIDS in title (5 as of Jan 2022)
- PubMed - 4 of many studies
- VitaminDWiki - Women category
The Effect of Vitamin D Deficiency on Overgrowth of Uterine Fibroids: A Blinded Randomized Clinical Trial
Int J Fertil Steril. 2021 Apr-Jun; 15(2): 95–100. doi: 10.22074/IJFS.2020.134567
Fatemeh Davari Tanha, M.D,1,2 Elham Feizabad, M.D,2,3,* Maryam Vasheghani Farahani, M.D,2 Hoora Amuzegar, M.D,2 Behnaz Moradi, M.D,4 and Saghar Samimi Sadeh, M.D5
Background: To evaluate the effects of vitamin D (vitD) supplement on uterine fibroid growth.
Materials and Methods
A randomized blinded clinical trial was conducted at a tertiary university-based hospital from August 2017 to September 2018. Totally, 204 women were enrolled into the study. They had at least one uterine fibroid >10 mm on transvaginal ultrasound and their vitD level was insufficient (i.e. 20-30 ng/ml). The intervention group was treated with vitD 50000 U supplements for two months. After 2 months, ultrasound screening and vitD level measurement was done in both groups.
At first, the mean serum vitD levels in intervention and control group were 23.62 and 23.20 ng/ml, respec- tively. After 8 weeks, the mean serum vitD levels in the control and intervention group were 22.72 and 28.56 ng/ml respectively (P<0.05). Also, mean fibroma diameter in the intervention group before and after 8 weeks of vitD supplementation was 43 ± 4.68 and 42.6 ± 1.31 mm, respectively. Mean uterine fibroid diameter in the control group which did not receive vitD supplements, before and after 8 weeks was 41.98 ± 5.25 and 47.81 ± 3.42 mm, respectively. The variation in the mean size of the uterine fibroid between the control and intervention group which was respectively about 5.83 mm increase and 0.48 mm decrease, was significant (P<0.001).
Our results showed that vitD supplementation prevents fibroid growth. It seems that vitD supplement is a simple, safe and inexpensive modality for leiomyoma growth prevention (Registration number: IRCT201703122576N15).
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All Uterine Fibroid studies found an inverse association with low vitamin D (helped by 4 of 5 interventions) – Review Aug 2022
A Systematic Review of Vitamin D and Fibroids: Pathophysiology, Prevention, and Treatment
Reprod Sci. 2022 Aug 12. doi: 10.1007/s43032-022-01011-z PDF is behind a paywall
Abigail Combs 1, Bhuchitra Singh 2, Elisabeth Nylander 3, Md Soriful Islam 2, Ha Vi Nguyen 2, Elissa Parra 2, Ameerah Bello 2, James Segars 4
Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential therapy for uterine fibroids based on experimental and epidemiologic evidence. The objective of this systematic review was to evaluate the role of vitamin D in the pathophysiology of uterine fibroids and its efficacy for prevention and treatment of fibroids. A comprehensive search was conducted of Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to March 2022. English-language publications that evaluated vitamin D and uterine fibroids in humans, whether experimental or clinical, were considered. The search yielded 960 publications, and 89 publications met inclusion criteria: 23 preclinical studies, 25 clinical studies, and 41 review articles. Preclinical studies indicated that the vitamin D receptor was decreased in fibroid cells. Vitamin D treatment of fibroid cells decreased proliferation, extracellular matrix protein expression, and Wnt/ß-catenin signaling. Fourteen clinical studies (n = 3535 participants) assessed serum vitamin D level in women with ultrasound-proven fibroids, and all found an inverse correlation between serum vitamin D level and presence of fibroids. Five clinical studies (n = 472 patients) evaluated treatment of fibroids with vitamin D.
Four of five studies showed vitamin D significantly inhibited fibroid growth.
One pilot study (n = 109 patients) of vitamin D for secondary prevention of fibroids demonstrated smaller recurrent fibroids in the treated group.
These studies provide evidence for vitamin D as a therapy for Uterine fibroids and underscore the need for well-designed, randomized, placebo-controlled clinical trials.
- Baird DD, Dunson DB, Hill MC, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100–7. - PubMed - DOI
- Cardozo ER, Clark AD, Banks NK, et al. The estimated annual cost of uterine leiomyomata in the United States. In: American Journal of Obstetrics and Gynecology. Mosby Inc., 2012, pp. 211.e1–211.e9.
- Parker WH. uterine myomas: management. Fertil Steril. 2007;88:255–71. - PubMed - DOI
- Bartels C, Cayton K, Chuong F, et al. An evidence-based approach to the medical management of fibroids: a systematic review. Clin Obstet Gynecol. 2016;59:30–52. - PubMed - DOI
- Schlaff WD, Ackerman RT, Al-Hendy A, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020;382:328–40. - PubMed - DOI
- Al-Hendy A, Lukes AS, Poindexter AN, et al. Treatment of uterine fibroid symptoms with relugolix combination therapy. N Engl J Med. 2021;384:630–42. - PubMed - PMC - DOI
- Corachán A, Ferrero H, Escrig J, et al. Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model. Fertil Steril. 2020;113:205-216.e4. - PubMed - DOI
- Al-Hendy A, Badr M. Can vitamin D reduce the risk of uterine fibroids? Women’s Health. 2014;10:353–8. - PubMed
- Bläuer M, Rovio PH, Ylikomi T, et al. Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro. Fertil Steril. 2009;91:1919–25. - PubMed - DOI
- Ciebiera M, Wlodarczyk M, Ciebiera M, et al. Vitamin D and uterine fibroids—review of the literature and novel concepts. Int J Mol Sci. 2018;19:2051. - PMC - DOI
- Baird DD, Hill MC, Schectman JM, et al. Vitamin D and the risk of uterine fibroids. Epidemiology. 2013;24:447–53. - PubMed - PMC - DOI
- Ali M, Al-Hendy A, Yang Q, Vitamin D. a promising natural compound with anti-uterine fibroid characteristics. Fertil Steril. 2019;111:268–9. - PubMed - DOI
- Ali M, Prince L, Al-Hendy A. Vitamin D and uterine fibroids: preclinical evidence is in; time for an overdue clinical study! Fertil Steril. 2020;113:89–90. - PubMed - DOI
- Wu JL, Segars JH. Is Vitamin D the answer for prevention of uterine fibroids? Fertil Steril. 2015;104:559–60. - PubMed - DOI
- Brakta S, Diamond JS, Al-Hendy A, et al. Role of vitamin D in uterine fibroid biology. Fertil Steril. 2015;104:698–706. - PubMed - PMC - DOI
- Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81. - PubMed - DOI
- Pike JW, Christakos S. Biology and mechanisms of action of the vitamin D hormone. Endocrinol Metab Clin North Am. 2017;46:815–43. - PubMed - PMC - DOI
- Spiro A, Buttriss JL. Vitamin D: an overview of vitamin D status and intake in Europe. Nutr Bull. 2014;39:322–50. - PubMed - PMC - DOI
- Webb AR. Who, what, where and when-influences on cutaneous vitamin D synthesis. Prog Biophys Mol Biol. 2006;92:17–25. - PubMed - DOI
- Zhao G, Ford ES, Tsai J, et al. Factors associated with vitamin D deficiency and inadequacy among women of childbearing age in the United States. ISRN Obstet Gynecol. 2012;2012: 691486. - PubMed - PMC - DOI
- WHO Scientific Group on the Prevention and Management of Osteoporosis (2000 : Geneva S. Prevention and management of osteoporosis : report of a WHO scientific group, https://apps.who.int/iris/handle/10665/42841 (2003).
- Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30. - PubMed - DOI
- Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012;97:1153–8. - PubMed - DOI
- Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81:353–73. - PubMed - DOI
- Ylikomi T, Laaksi I, Lou Y-R, et al. Antiproliferative action of vitamin D. Vitam Horm. 2002;64:357–406. - PubMed - DOI
- Halder SK, Sharan C, Al-Hendy A. 1,25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. Biol Reprod. 2012;86:1–10. - DOI
- Halder SK, Osteen KG, Al-Hendy A. 1,25-Dihydroxyvitamin D3 reduces extracellular matrix-associated protein expression in human uterine fibroid cells. Biol Reprod. 2013;89:1–13. - DOI
- Al-Hendy A, Diamond MP, Boyer TG, et al. Vitamin D3 inhibits Wnt/ß-catenin and mTOR signaling pathways in human uterine fibroid cells. J Clin Endocrinol Metab. 2016;101:1542–51. - PubMed - PMC - DOI
- Corachán A, Ferrero H, Aguilar A, et al. Inhibition of tumor cell proliferation in human uterine leiomyomas by vitamin D via Wnt/ß-catenin pathway. Fertil Steril. 2019;111:397–407. - PubMed - DOI
- Ali M, Shahin SM, Sabri NA, et al. Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment. Acta Pharmacol Sin. 2019;40:957–70. - PubMed - DOI
- Halder SK, Goodwin JS, Al-Hendy A. 1,25-Dihydroxyvitamin D3 reduces TGF-ß3-induced fibrosis-related gene expression in human uterine leiomyoma cells. J Clin Endocrinol Metab. 2011;96:E754–62. - PubMed - PMC - DOI
- Halder SK, Osteen KG, Al-Hendy A. Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum Reprod. 2013;28:2407–16. - PubMed - PMC - DOI
- Sharan C, Halder SK, Thota C, et al. Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. Fertil Steril. 2011;95:247–53. - PubMed - DOI
- Othman ER, Ahmed E, Sayed AA, et al. Human uterine leiomyoma contains low levels of 1, 25 dihdroxyvitamin D3, and shows dysregulated expression of vitamin D metabolizing enzymes. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2018;229:117–22. - PubMed - DOI
- Fritton K, Borahay MA. New and emerging therapies for uterine fibroids. Seminars in Reproductive Medicine. 2017;35:549–59. - PubMed - DOI
- Parazzini F, di Martino M, Candiani M, et al. Dietary components and uterine leiomyomas: a review of published data. Nutr Cancer. 2015;67:569–79. - PubMed - DOI
- Ciebiera M, Lukaszuk K, Meczekalski B, et al. Alternative oral agents in prophylaxis and therapy of uterine fibroids—an up-to-date review. Int J Mol Sci. 2017;18:2856.
- Halder S, Al-Hendy A. Hypovitaminosis D and high serum transforming growth factor beta-3: important biomarkers for uterine fibroids risk. Fertil Steril. 2016;106:1648–9. - PubMed - PMC - DOI
- Islam MS, Akhtar MM, Segars JH. Vitamin D deficiency and uterine fibroids: an opportunity for treatment or prevention? Fertil Steril. 2021;115:1175–6. - PubMed - DOI
- Sterne JAC, Savovic J, Page MJ, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. The BMJ. 2019;366:1–8.
- Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. - PubMed - DOI
- Sabry M, Halder SK, Ait Allah ASA, et al. Serum vitamin D3 level inversely correlates with uterine fibroid volume in different ethnic groups: a cross-sectional observational study. International Journal of Women’s Health. 2013;5:93–100. - PubMed - PMC
- Paffoni A, Somigliana E, Vigano P, et al. Vitamin D status in women with uterine leiomyomas. Journal of Clinical Endocrinology and Metabolism 2013; 98: E1374–E1378.
- Mitro SD, Zota AR. Vitamin D and uterine leiomyoma among a sample of US women: findings from NHANES, 2001–2006. Reprod Toxicol. 2015;57:81–6. - PubMed - PMC - DOI
- Ciebiera M, Wlodarczyk M, Slabuszewska-Józwiak A, et al. Influence of vitamin D and transforming growth factor ß3 serum concentrations, obesity, and family history on the risk for uterine fibroids. Fertil Steril. 2016;106:1787–92. - PubMed - DOI
- Oskovi Kaplan ZA, Tasçi Y, Topçu HO, et al. 25-Hydroxy vitamin D levels in premenopausal Turkish women with uterine leiomyoma. Gynecol Endocrinol. 2018;34:261–4. - PubMed - DOI
- Singh V, Barik A, Imam N. Vitamin D 3 level in women with uterine fibroid: an observational study in eastern Indian population. Journal of Obstetrics and Gynecology of India. 2019;69:161–5. - PubMed - DOI
- Srivastava P, Gupta HP, Singhi S, et al. Evaluation of 25-hydroxy vitamin D3 levels in patients with a fibroid uterus. J Obstet Gynaecol. 2020;40:710–4. - PubMed - DOI
- Farzaneh F, Sadeghi K, Chehrazi M. Vitamin D status in women with uterine fibroids: a cross-sectional study. Open Access Macedonian Journal of Medical Sciences. 2020;8:109–13. - DOI
- Li S, Chen B, Sheng B, et al. The associations between serum vitamin D, calcium and uterine fibroids in Chinese women: a case-controlled study. J Int Med Res. 2020;48:1–11.
- Irnazarova DK, Yuldasheva DK, Najmutdinova DK, et al. Influence of excess body weight and deficiency of vitamin D on the clinical course of uterine myoma. European Journal of Molecular and Clinical Medicine. 2020;7:3317–29.
- Tunau KA, Garba JA, Panti AA, et al. Low plasma vitamin D as a predictor of uterine fibroids in a Nigerian population. Niger Postgrad Med J. 2021;28:181–6. - PubMed - DOI
- Sarbhai V, Ajmani SN, Singh S. Correlation of the levels of vitamin d with size of leiomyoma in a 450-bedded maternity hospital of Delhi. Journal of SAFOG. 2021;13:77–80. - DOI
- Huseman-Plascencia LA, Villa-Villagrana F, Ballesteros-Manzo A, et al. Body mass index and vitamin D as risk factors for the development of uterine leiomyomas in Mexican women. Journal of Endometriosis and Pelvic Pain Disorders. 2021;00:1–5.
- Xu F, Li F, Li L, et al. Vitamin D as a risk factor for the presence of asymptomatic uterine fibroids in premenopausal Han Chinese women. Fertil Steril. 2021;115:1288–93. - PubMed - DOI
- Mohammadi R, Tabrizi R, Hessami K, et al. Correlation of low serum vitamin-D with uterine leiomyoma: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2020;18:1–8. - DOI
- Ali M, Shahin SM, Sabri NA, et al. 1,25 Dihydroxyvitamin D3 enhances the antifibroid effects of ulipristal acetate in human uterine fibroids. Reprod Sci. 2019;26:812–28. - PubMed - DOI
- Corachán A, Trejo MG, Carbajo-García MC, et al. Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation. Fertil Steril. 2021;115:512–21. - PubMed - DOI
- Al-Hendy A, Diamond MP, El-Sohemy A, et al. 1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells. J Clin Endocrinol Metab. 2015;100:E572–82. - PubMed - PMC - DOI
- Liu F, Zhang X, Yan K, et al. Vitamin D receptor and cyclooxygenase-2 expression in uterine leiomyoma tissues and their correlation. Translational Cancer Research. 2018;7:135–41. - DOI
- Fazeli E, Piltan S, Gholami M, et al. CYP24A1 expression analysis in uterine leiomyoma regarding MED12 mutation profile. Arch Gynecol Obstet. 2021;303:787–92. - PubMed - DOI
- Cross CI, Driggers PH, McCarthy BE, et al. A-kinase anchoring protein 13 interacts with the vitamin D receptor to alter vitamin D-dependent gene activation in uterine leiomyoma cells. F&S Science. 2021;2:303–14. - DOI
- Lima MSO, da Silva BB, de Medeiros ML, et al. Evaluation of vitamin D receptor expression in uterine leiomyoma and nonneoplastic myometrial tissue: a cross-sectional controlled study. Reprod Biol Endocrinol. 2021;19:1–6. - DOI
- Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7:684–700. - PubMed - DOI
- Wolanska M, Sobolewski K, Bankowski E, et al. Matrix metalloproteinases of human leiomyoma in various stages of tumor growth. Gynecol Obstet Invest. 2004;58:14–8. - PubMed - DOI
- Mehine M, Mäkinen N, Heinonen HR, et al. Genomics of uterine leiomyomas: insights from high-throughput sequencing. Fertil Steril. 2014;102:621–9. - PubMed - DOI
- Manousaki D, Mitchell R, Dudding T, et al. Genome-wide association study for vitamin D levels reveals 69 independent loci. Am J Hum Genet. 2020;106:327–37. - PubMed - PMC - DOI
- Kiel DP, Cheung C, Karasik D, et al. Articles common genetic determinants of vitamin D insufficiency: a genome-wide association study. The Lancet. 2010;376:180–8. - DOI
- Wise LA, Ruiz-Narváez EA, Haddad SA, et al. Polymorphisms in vitamin D-related genes and risk of uterine leiomyomata. Fertil Steril. 2014;102:503–10. - PubMed - PMC - DOI
- Shahbazi S, Alavi S, Majidzadeh-A K, et al. BsmI but not FokI polymorphism of VDR gene is contributed in breast cancer. Med Oncol. 2013;30:1–6. - DOI
- Chen WY, Bertone-Johnson ER, Hunter DJ, et al. Associations between polymorphisms in the vitamin D receptor and breast cancer risk. Cancer Epidemiol Biomark Prev. 2005;14:2335–9. - DOI
- Alimirah F, Peng X, Murillo G, et al. Functional significance of vitamin D receptor Foki polymorphism in human breast cancer cells. PLoS ONE. 2011;6: e16024. - PubMed - PMC - DOI
- Shahbazi S. Exploring the link between VDR rs2228570 and uterine leiomyoma in Iranian women. Egyptian Journal of Medical Human Genetics. 2016;17:115–8. - DOI
- Yilmaz SG, Gül T, Attar R, et al. Association between fok1 polymorphism of vitamin d receptor gene with uterine leiomyoma in Turkish populations. Journal of the Turkish German Gynecology Association. 2018;19:128–31. - DOI
- Ciebiera M, Wrzosek M, Wojtyla C, et al. Vitamin D receptor gene polymorphisms and uterine fibroid incidence in Caucasian women. Arch Med Sci. 2019;17:1643–50. - PubMed - PMC
- Chun RF. New perspectives on the vitamin D binding protein. Cell Biochem Funct. 2012;30:445–56. - PubMed - DOI
- Powe CE, Evans MK, Wenger J, et al. Vitamin D-binding protein and vitamin D status of Black Americans and White Americans. N Engl J Med. 2013;369:1991–2000. - PubMed - PMC - DOI
- Arnaud J, Constans J. Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993;92:183–8. - PubMed - DOI
- Bateman NW, Tarney CM, Abulez TS, et al. Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry. iScience 2022; 25: 1–20.
- Lin C-P, Chen Y-W, Liu W-H, et al. Proteomic identification of plasma biomarkers in uterine leiomyoma. Mol BioSyst. 2012;8:1136–45. - PubMed - DOI
- Ciavattini A, Carpini GD, Serri M, et al. Hypovitaminosis D and “small burden” uterine fibroids: opportunity for a Vitamin D supplementation. Medicine (United States). 2016;95:1–8.
- Hajhashemi M, Ansari M, Haghollahi F, et al. The effect of Vitamin D supplementation on the size of uterine leiomyoma in women with Vitamin D deficiency. Caspian J Intern Med. 2019;10:125–31. - PubMed - PMC
- Arjeh S, Darsareh F, Asl ZA, et al. Effect of oral consumption of vitamin D on uterine fibroids: a randomized clinical trial. Complement Ther Clin Pract. 2020;39:1–5. - DOI
- Suneja A, Faridi F, Bhatt S, et al. Effect of Vitamin D3 supplementation on symptomatic uterine leiomyoma in women with Hypovitaminosis D. Journal of Mid-Life Health. 2021;12:53–60. - PubMed - PMC - DOI
- Tanha FD, Feizabad E, Farahani MV, et al. The effect of Vitamin D deficiency on overgrowth of uterine fibroids: a blinded randomized clinical trial. International Journal of Fertility and Sterility. 2021;15:95–100.
- Porcaro G, Santamaria A, Giordano D, et al. Vitamin D plus epigallocatechin gallate: a novel promising approach for uterine myomas. Eur Rev Med Pharmacol Sci. 2020;24:3344–51. - PubMed
- Miriello D, Galanti F, Cignini P, et al. uterine fibroids treatment: do we have new valid alternative? Experiencing the combination of vitamin D plus epigallocatechin gallate in childbearing age affected women. Eur Rev Med Pharmacol Sci. 2021;25:2843–51. - PubMed
- Grandi G, del Savio MC, Melotti C, et al. Vitamin D and green tea extracts for the treatment of uterine fibroids in late reproductive life: a pilot, prospective, daily-diary based study. Gynecol Endocrinol. 2022;38:63–7. - PubMed - DOI
- Ciebiera M, Meczekalski B, Lukaszuk K, et al. Potential synergism between ulipristal acetate and vitamin D3 in uterine fibroid pharmacotherapy–2 case studies. Gynecol Endocrinol. 2019;35:473–7. - PubMed - DOI
- Roshdy E, Rajaratnam V, Maitra S, et al. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. International Journal of Women’s Health. 2013;5:477–86. - PubMed - PMC
- Vahdat M, Allahqoli L, Mirzaei H, et al. The effect of vitamin D on recurrence of uterine fibroids: a randomized, double-blind, placebo-controlled pilot study. Complement Ther Clin Pract. 2022;46:1–5. - DOI
- Catherino W, Eltoukhi H, Al-Hendy A. Racial and ethnic differences in the pathogenesis and clinical manifestations of uterine leiomyoma. Seminars in Reproductive Medicine. 2013;31:370–9. - PubMed - PMC - DOI
- Islam MS, Protic O, Giannubilo SR, et al. uterine leiomyoma: available medical treatments and new possible therapeutic options. J Clin Endocrinol Metab. 2013;98:921–34. - PubMed - DOI
- Borahay MA, al Hendy A, Kilic GS, et al. Signaling pathways in leiomyoma: understanding pathobiology and implications for therapy. Molecular Medicine 2015; 21: 242–256.
- Buggio L, Roncella E, Somigliana E, et al. Vitamin D and benign gynaecological diseases: a critical analysis of the current evidence. Gynecol Endocrinol. 2016;32:259–63. - PubMed - DOI
- Skowronska P, Pastuszek E, Kuczynski W, et al. The role of vitamin D in reproductive dysfunction in women—a systematic review. Ann Agric Environ Med. 2016;23:671–6. - PubMed - DOI
- Nandi A, Sinha N, Ong E, et al. Is there a role for vitamin D in human reproduction? Horm Mol Biol Clin Invest. 2016;25:15–28.
- Sparic R, Mirkovic L, Malvasi A, et al. Epidemiology of uterine myomas: a review citation: Sparic R, Mirkovic L, Malvasi A, Tinelli A. Epidemiology of uterine myomas: a review. Int J Fertil Steril. Royan Institute International Journal of Fertility and Sterility 2016; 9: 424–435.
- Arslan S, Akdevelioglu Y. The relationship between female reproductive functions and vitamin D. J Am Coll Nutr. 2018;37:546–51. - PubMed - DOI
- ElKafas H, Ali M, Al-Hendy A. Leiomyomas. Encyclopedia of Reproduction 2018; 101–105.
- Islam MS, Ciavattini A, Petraglia F, et al. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update. 2018;24:59–85. - PubMed - DOI
- A. Markowska WBRJACJMarkowska. uterine fibroids: a new insight into an old problem. Eur J Gynaecol Oncol 2019; 40: 915–918.
- Ciebiera M, Ali M, Prince L, et al. The evolving role of natural compounds in the medical treatment of uterine fibroids. J Clin Med. 2020;9:1–31. - DOI
- Ciebiera M, Ali M, Zgliczynska M, et al. Vitamins and uterine fibroids: current data on pathophysiology and possible clinical relevance. Int J Mol Sci. 2020;21:1–25.
- Fichera M, Török P, Tesarik J, et al. Vitamin D, reproductive disorders and assisted reproduction: evidences and perspectives. Int J Food Sci Nutr. 2020;71:276–85. - PubMed - DOI
- Judson I, Messiou C. Vitamin D deficiency in the pathogenesis of leiomyoma and intravascular leiomyomatosis: a case report and review of the literature. Gynecologic Oncology Reports. 2021;35: 100681. - PubMed - DOI
- Ciebiera M, Ali M, Prince L, et al. The significance of measuring Vitamin D serum levels in women with uterine fibroids. Reprod Sci. 2021;28:2098–109. - PubMed - DOI
- AlAshqar A, Reschke L, Kirschen GW, et al. Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies. Biol Reprod. 2021;105:7–31. - PubMed - PMC - DOI
- Ciebiera M, Esfandyari S, Siblini H, et al. Nutrition in gynecological diseases: current perspectives. Nutrients. 2021;13:1178. - PubMed - PMC - DOI
- Chu TW, Jhao JY, Lin TJ, et al. Vitamin D in gynecological diseases. J Chin Med Assoc. 2021;84:1054–9. - PubMed - DOI
- Afrin S, Alashqar A, el Sabeh M, et al. Diet and nutrition in gynecological disorders: a focus on clinical studies. Nutrients. 2021;13:1747. - PubMed - PMC - DOI
- Elkafas H, Badary O, Elmorsy E, et al. Endocrine-disrupting chemicals and Vitamin D deficiency in the pathogenesis of uterine fibroids. Journal of Advanced Pharmacy Research. 2021;5:248–63. - DOI
- Vergara D, Catherino WH, Trojano G, et al. Vitamin D: mechanism of action and biological effects in uterine fibroids. Nutrients. 2021;13:1–11.
- el Sabeh M, Borahay MA. The future of uterine fibroid management: a more preventive and personalized paradigm. Reprod Sci. 2021;28:3285–8. - PubMed - DOI
- Purusothaman V, Young SL. Vitamin D and uterine leiomyomata: is it time to let the sunshine in? Fertil Steril. 2021;115:340–1. - PubMed - DOI
- Szydlowska I, Nawrocka-Rutkowska J, Brodowska A, et al. Dietary natural compounds and vitamins as potential cofactors in uterine fibroids growth and development. Nutrients. 2022;14:734. - PubMed - PMC - DOI
- Ferrero H. Growth disparities in uterine leiomyomas associated with MED12 mutation. Fertil Steril. 2019;111:58–9. - PubMed - DOI
- Al-Hendy A. Burden of uterine fibroids: an African perspective, a call for action and opportunity for intervention current opinion in gynecology and obstetrics. Cur Op Gyn Obs. 2019;2:287–94.
- Sheng B, Song Y, Liu Y, et al. Association between vitamin D and uterine fibroids: a study protocol of an open-label, randomised controlled trial. BMJ Open. 2020;10:1–8. - DOI
Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation -Nov 2020
Fertil Steril. 2020 Oct 7;S0015-0282(20)30710-X. doi: 10.1016/j.fertnstert.2020.07.049
Ana Corachán 1, María Gabriela Trejo 1, María Cristina Carbajo-García 2, Javier Monleón 3, Julia Escrig 3, Amparo Faus 1, Antonio Pellicer 4, Irene Cervelló 1, Hortensia Ferrero 5
Objective: To study whether vitamin D (VitD) inhibits cell proliferation and Wnt/β-catenin and transforming growth factor-β (TGFβ) signaling pathways in uterine leiomyomas independent of mediator complex subunit 12 (MED12) mutation status.
Design: Prospective study comparing leiomyoma vs. myometrial tissues and human uterine leiomyoma primary (HULP) cells treated with or without VitD and analyzed by MED12 mutation status.
Setting: Hospital and university laboratories.
Patient(s): Women with uterine leiomyoma without any treatment (n = 37).
Intervention(s): Uterine leiomyoma and myometrium samples were collected from women undergoing surgery because of symptomatic leiomyoma pathology.
Main outcome measure(s): Analysis of Wnt/β-catenin and TGFβ pathways and proliferation by quantitative real-time polymerase chain reaction in leiomyoma and myometrial tissue as well as in VitD-treated HULP cells analyzed by Sanger sequencing.
Results: Sequencing data showed that 46% of leiomyomas presented MED12 mutation, whereas no mutations were detected in adjacent myometrium. Expression of Wnt/β-catenin and TGFβ pathway genes was significantly increased in MED12-mutated leiomyomas compared to matched myometrium; no significant differences were found in wild-type (WT) leiomyomas. In HULP cells, VitD significantly decreased PCNA expression of both MED12-mutated and WT groups. VitD treatment decreased WNT4 and β-catenin expression in both groups compared to controls, with significance for WNT4 expression in MED12-mutated samples. Similarly, VitD significantly inhibited TGFβ3 expression in cells from both groups. MMP9 expression also decreased.
Conclusion: Despite molecular differences between MED12-mutated and WT leiomyomas, VitD inhibited Wnt/β-catenin and TGFβ pathways in HULP cells, suggesting VitD as an effective treatment to reduce proliferation and extracellular matrix formation in different molecular subtypes of uterine leiomyomas.
Nutrients 2021, 13(2), 597; https://doi.org/10.3390/nu13020597
by Daniele Vergara 1,*ORCID,William H. Catherino 2,3,Giuseppe Trojano 4 and Andrea Tinelli 5,6,7ORCID
Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.
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The effect of vitamin D on recurrence of uterine fibroids: A randomized, double-blind, placebo-controlled pilot study
Complementary Therapies in Clinical Practice, Volume 46, February 2022, 101536 https://doi.org/10.1016/j.ctcp.2022.101536
- Vitamin D reduced recurrence rates of uterine fibroids by 50%.
- Vitamin D reduced the size of recurrent uterine fibroids.
- Vitamin D is a safe agent in the prevention of recurrence and reduction of the size of recurrent uterine fibroids.
and purpose: A deficiency of vitamin D has been suggested as one of the principal risk factors for uterine fibroids (UFs). We aimed to investigate the effect of vitamin D supplementation on the recurrence of UFs.
Materials and methods
In a randomized, double-blind, placebo-controlled pilot study, women who had undergone hysteroscopic myomectomy from November 2017 to June 2020 were randomly given either vitamin D (1000 IU tablet; n = 55), or placebo (n = 54) daily for 12 months. Both groups were followed and compared in regard of the primary outcomes of the study, which were recurrence rates, size, and numbers of UFs based on three-dimensional transvaginal ultrasound investigation (3D-TVS). Data analysis was performed by the intention-to-treat (ITT) approach.
The mean age of the study participants was 37.9 ± 6.5 years. The two groups did not differ significantly in terms of demographic and pre-intervention clinical characteristics. The administration of vitamin D supplements for one year reduced recurrence rates of UFs by 50% (p = 0.17). Vitamin D also reduced the size of recurrent UFs in the intervention group compared to controls (−7.7 mm), the difference was statistically different (p < 0.001). No adverse effect of vitamin D was reported in the present study.
Based on these results, vitamin D appears to be a promising and safe agent in the prevention of recurrence and reduction of the size of recurrent UFs, although further well-designed and appropriately powered studies are required to demonstrate a significant difference in the size and number of recurrent UFs.
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This list is automatically updated
- Vitamin D and Risk of Uterine Fibroids - May 2013 Hollis PDF
- Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts - July 2018 PDF
- Hypovitaminosis D and “small burden” uterine fibroids: Opportunity for a vitamin D supplementation - PDF
- The Significance of Measuring Vitamin D Serum Levels in Women with Uterine Fibroids - Oct 2020 PDF
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