Vitamin D deficiency and uterine leiomyoma in unexplained infertility

Uterine leiomyomas are the most common benign tumors of the female genital tract, and alongside hormonal and genetic factors, emerging evidence implicates vitamin D deficiency in their pathogenesis. We investigated the association between serum 25-hydroxyvitamin D [25(OH)D] and the presence of uterine leiomyomas in women with unexplained infertility. In this retrospective case-control study, 148 women aged 18-45 years presenting to the Infertility Clinic of Ankara Bilkent City Hospital between July 2019 and February 2024 were included: 74 had imaging-confirmed leiomyomas (non-submucosal; FIGO types 4-6) and 74 infertile controls had no leiomyomas. Serum 25(OH)D was measured and demographic/clinical data were analyzed with appropriate parametric and non-parametric tests; correlations used Spearman's rho, and an ANCOVA adjusted for body mass index (BMI) and season assessed group differences. Groups were comparable in age and BMI (e.g., age 35.08 ± 5.79 vs 33.30 ± 5.57 years; p = 0.062). Mean serum 25(OH)D was significantly lower in women with leiomyomas than in controls (41.4 ± 23.7 vs 62.0 ± 34.2 nmol/L; p < 0.001), and this difference remained significant after adjustment for BMI and season (ANCOVA F = 10.7, p = 0.001). Vitamin D levels did not differ by leiomyoma number (single vs multiple: 44.1 ± 21.6 vs 38.5 ± 25.83 nmol/L; p = 0.32) or location (intramural vs subserosal: 40.7 ± 24.9 vs 43.1 ± 21.1 nmol/L; p = 0.69), and were not correlated with leiomyoma size (Spearman r = -0.04; p = 0.70). Among women with unexplained infertility, uterine leiomyomas are thus associated with significantly lower serum 25(OH)D levels, independent of BMI and season, whereas vitamin D status is unrelated to leiomyoma number, size, or location. These findings support a potential role of vitamin D deficiency in leiomyoma pathogenesis and underscore the need for larger, multicenter prospective studies to clarify causality and clinical implications.