Vitamin d and the risk of uterine fibroids

Abstract

Background: Uterine leiomyomata (also known as fibroids) are benign tumors of uterine smooth muscle that are characterized by overproduction of extracellular matrix. Fibroids are the leading indication for hysterectomy in the United States. The active metabolite of vitamin D has been shown to inhibit cell proliferation and extracellular matrix production in fibroid tissue culture and to reduce fibroid volume in the Eker rat. No previous study has examined whether vitamin D is related to fibroid status in women.

Methods: The National Institute of Environmental Health Sciences Uterine Fibroid Study enrolled randomly selected 35- to 49-year-old women who were members of an urban health plan during 1996-1999. Fibroid status was determined by ultrasound screening of premenopausal women (620 blacks, 416 whites). Vitamin D status was assessed in stored plasma by radioimmunoassay of 25-hydroxyvitamin D (25(OH)D) and questionnaire data on sun exposure. Associations were evaluated with logistic regression, controlling for potential confounders.

Results: Only 10% of blacks and 50% of whites had levels of 25(OH)D regarded as sufficient (>20 ng/ml). Women with sufficient vitamin D had an estimated 32% lower odds of fibroids compared with those with vitamin D insufficiency (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] = 0.48-0.96). The association was similar for blacks and whites. Self-reported sun exposure ≥ 1 hour per day (weather permitting) was also associated with reduced odds of fibroids (aOR = 06. [0.4-0.9]), with no evidence of heterogeneity by ethnicity.

Conclusions: The consistency of findings for questionnaire and biomarker data, the similar patterns seen in blacks and whites, and the biological plausibility provide evidence that sufficient vitamin D is associated with a reduced risk of uterine fibroids.

Figure 1

Participation and sample selection, NIEHS Uterine Fibroid Study.

Figure 2

Association between 25(OH)D concentration and fibroid prevalence in total sample (top panel), blacks (middle panel), and whites (lower panel). The distribution of 25(OH)D is shown in the bottom section of each panel. The solid. heavy straight line on each panel shows the estimated decline in fibroid prevalence associated with linearly increasing 25(OH)D. The adjusted odds ratios associated with each 10 ng/ml increase in 25(OH)D concentration are shown to the right of these lines. The estimated adjusted odds ratios for fibroids associated with each 5-unit category of the 25(OH)D concentration are plotted with their 95% confidence intervals to allow for visual assessment of linearity. When sample size for a single 5-unit category was small, adjacent categories were combined and plotted at the mean value for the combined category, e.g., the last aOR plotted for the total sample is for the combined group of women with 25(OH)D >30 ng/ml, plotted at the mean for the category, 34.8 ng/ml. The left shaded area represents vitamin D insufficiency (≤20 ng/ml), and the adjusted odds ratio for fibroid prevalence associated with sufficient vitamin D is shown at the top right of each panel. All analyses adjusted for age, age of menarche, full-term pregnancies after age 24, body mass index, and physical activity. Analyses shown in the top panel (total sample) also adjust for ethnicity.