Influence of Vitamin D on the Growth and Development of Uterine Fibroids

Uterine fibroids represent the most frequently encountered benign gynecological tumors in women of reproductive age. Key risk factors include vitamin D deficiency, obesity, dark skin pigmentation, low parity, premenopausal status, hereditary/hormonal backgrounds, and heavy alcohol consumption. Although benign, fibroids severely diminish the quality of life via symptoms such as abnormal uterine bleeding, pelvic pressure, urinary frequency/retention, anemia, infertility, and poor obstetric outcomes. Current surgical, medical, and interventional therapies impose immense financial burdens on health systems while carrying substantial procedural risks and drug side effects, necessitating safe alternative treatments. A systematic literature search was conducted following PRISMA guidelines. PubMed Central (PMC) and Google Scholar were searched from inception through (July 2023 to 2025) using the following search string: ("Vitamin D" OR "cholecalciferol" OR "ergocalciferol" OR "1,25-dihydroxyvitamin D" OR "vitamin D deficiency") AND ("uterine fibroids" OR "uterine leiomyoma" OR "leiomyomata") AND ("in vitro" OR "in vivo" OR "animal model" OR "clinical trial" OR "epidemiology" OR "demographics"). Inclusion criteria comprised peer-reviewed human clinical trials, in vivo animal studies, and in vitro investigations evaluating vitamin D's relationship, molecular mechanisms, or therapeutic effects on uterine fibroids, including demographic disparities, published in English. Editorials, conference abstracts, narrative reviews, and studies focusing on other gynecological conditions were excluded. Study selection involved duplicate removal, independent title/abstract screening, and full-text assessment, with disagreements resolved by consensus. Risk of bias was independently assessed using the Cochrane Risk of Bias (RoB) 2 and Newcastle-Ottawa Scale for human studies, Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE) tool for animal models, and tailored quality parameters for in vitro studies. Due to methodological heterogeneity, a qualitative narrative synthesis was performed rather than a meta-analysis. Synthesized data confirm that uterine fibroid tissue is highly correlated with deficient vitamin D levels. Mechanistically, vitamin D exerts antiproliferative effects, mitigates cellular DNA damage, and modulates estrogen and progesterone receptor (PR) expression within fibroid cells. In vitro and in vivo animal models demonstrate the high efficacy of vitamin D in suppressing leiomyoma growth. Similarly, existing clinical trials support its role in regressing physical fibroid size and volume without causing significant adverse effects. Vitamin D presents a safe, well-tolerated, and highly cost-effective therapeutic option for uterine fibroids, particularly for patients seeking fertility preservation or those deemed surgically unfit. While current data are highly promising and capable of reducing global healthcare burdens, large-scale randomized clinical trials (RCTs) and robust meta-analyses are urgently required. Expanding this research will establish definitive clinical guidelines regarding standardized dosing, treatment duration, and precise patient selection criteria based on age, symptoms, and surgical fitness.