Dr. Ron’s Research Review – February 10, 2016

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This week’s research review focuses on vitamin D for uterine fibroids.

Vitamin D is the main regulator of calcium homeostasis. Vitamin D3 also functions as a strong anti-fibrotic factor. Recent studies have demonstrated that vitamin D3 is a potent antitumor agent that effectively inhibits human uterine fibroid cells in vitro and shrinks fibroid lesions in preclinical animal studies; however, no human trials have been conducted in this area thus far. (Al-Hendy and Badr, 2014)

A recent article showed that in vitro, vitamin D3 functions as an antagonist of sex steroid hormone receptors in human uterine leiomyoma cells. Treatment with 1,25(OH)2D3 significantly decreased levels of ER-α, PR-A, and PR-B. 1,25(OH)2D3 functions as a potent anti-estrogenic/anti-progesteronic agent (Al-Hendy et al., 2015)

The National Institute of Environmental Health Sciences Uterine Fibroid Study Fibroid determined fibroid status was by ultrasound screening of premenopausal women (620 blacks, 416 whites). 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. (Baird et al., 2013)

Dr. Ron


 

Articles

Can vitamin D reduce the risk of uterine fibroids
            (Al-Hendy and Badr, 2014) Download

1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells.
            (Al-Hendy et al., 2015) Download
CONTEXT:  Uterine fibroids (UFs) are the most common benign tumors in premenopausal women. In this study, we evaluated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the treatment of UFs. OBJECTIVE:  To determine the role of 1,25(OH)2D3 on the expression of sex steroid receptors in human UF cells. DESIGN:  Human UFs and their adjacent myometrium were analyzed for expression of estrogen receptor (ER)-α, progesterone receptor (PR)-A, and PR-B, as well as members of the steroid receptor coactivator (SRC) family. Immortalized human uterine fibroid (human uterine leiomyoma [HuLM]) cells were treated with 1,25(OH)2D3 and assayed for the expression and localization of the aforementioned receptors and SRCs using Western blot, immunohistochemistry, immunofluorescence, and immunoprecipitation assays. MAIN OUTCOME MEASURES:  We discovered a correlation between reduced levels of vitamin D receptor (VDR) and increased levels of ER-α, PR-A, and PR-B in these tissues. We evaluated the effects of 1,25(OH)2D3 on the regulation of the aforementioned sex steroid receptors. RESULTS:  We observed an inverse correlation between the up-regulated ER-α, PR-A, and PR-B and expression of VDR in UFs. Treatment with 1,25(OH)2D3 significantly decreased levels of ER-α, PR-A, and PR-B, as well as SRCs in HuLM cells (P < .05). In contrast, 1,25(OH)2D3 self-induced its own VDR, which resulted in an induction of VDR-retinoid X receptor-α complex in HuLM cells. Together, these results suggest that 1,25(OH)2D3 functions as an antagonist of sex steroid hormone receptors in HuLM cells. CONCLUSIONS:  1,25(OH)2D3 functions as a potent antiestrogenic/antiprogesteronic agent that may have utility as a novel therapeutic option for UF.


 

Vitamin d and the risk of uterine fibroids
            (Baird et al., 2013) Download
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.

References

Al-Hendy, A and M Badr (2014), ‘Can vitamin D reduce the risk of uterine fibroids’, Womens Health (Lond Engl), 10 (4), 353-58. PubMed: 25259897
Al-Hendy, A, et al. (2015), ‘1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells.’, J Clin Endocrinol Metab, 100 (4), E572-82. PubMed: 25625804
Baird, D. D., et al. (2013), ‘Vitamin d and the risk of uterine fibroids’, Epidemiology, 24 (3), 447-53. PubMed: 23493030