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The synergism of vitamin D and estradiol deficiency on metabolic syndrome

21 October, 2019:  


Recent publications have shown that estrogens and vitamin D have a synergistic effect, not only on bone health but also on insulin resistance and metabolic syndrome [1,2,3]. Underlying mechanisms for these associations are not clear and several possible explanations have been suggested. Vitamin D may have an insulinotropic effect by increasing intracellular calcium concentration in pancreatic beta-cells. Vitamin D may also act as an inhibitor of sterol regulatory element-binding proteins activation, thus controlling lipid homeostasis. Finally, vitamin D levels affect the nitric oxide signaling pathway in the arterial muscle, leading to an abnormal vasodilator activity [2,4,5]. Clinical trials have also reported that vitamin D supplementation may reduce visceral adipose tissue in overweight or obese adults [6].

Hui Huang and his group carried out an observational and cross-sectional study [7], evaluating 616 postmenopausal women (aged 49-86 y) from southern China, who were not taking estrogen and vitamin D or calcium supplements, to assess the role of vitamin D levels in relation to metabolic syndrome and estradiol (E2) levels. The participants were classified into two groups based on vitamin D levels (25(OH)D < or ≥ 50 nmol/L). In participants with optimal serum levels of vitamin D (≥ 50 nmol/L), there was no significant correlation between estradiol and metabolic syndrome, after adjusting for confounding factors. In the other group of women,  the adjusted odds ratio (OR) for metabolic syndrome significantly increased with decreasing serum 25(OH)D (OR 2.19, 95% CI, 1.19-4.01 for comparisons of vitamin D deficient versus sufficient; P for trend 0.009). This association remained unchanged after further adjusting for estrogen levels. Postmenopausal women who were vitamin D deficient presented a negative correlation between estradiol levels and metabolic syndrome risk (OR 3.49, 95% CI, 1.45-8.05 for the lowest versus the highest tertile; P for trend 0.006). The present study observed that vitamin D deficiency is an independent risk factor for metabolic syndrome in postmenopausal women. Moreover, the authors observed an inverse association between estradiol levels and metabolic syndrome, which tends to be stronger in participants with vitamin D deficiency than in those with adequate circulating levels of the vitamin.


The risk of cardiovascular disease increases after menopause and may be related to the substantial metabolic changes that take place as women transition from premenopause to postmenopause. The prevalence of metabolic syndrome increases with age. Many cross-sectional studies have shown an increased risk of metabolic syndrome in postmenopausal women, which varies from 32.6% to 41.5% [8,9]. In medical literature, observational studies suggest that vitamin D plays a role in the pathogenesis of type 2 diabetes [10]. However, the results of intervention studies have been inconsistent [11, 12]. This observational study emphasizes the possible synergistic role of vitamin D and estradiol deficiency in causing metabolic syndrome in postmenopausal women. If these results are confirmed in randomized controlled trials, correction of inappropriate levels of vitamin D may become widespread in clinical practice, not only to preserve bone but reduce the manifestations of the metabolic syndrome and its consequences.

Sonia Cerdas

Endocrinologist, Hospital Cima, University of Costa Rica, Costa Rica


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  12. Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O'Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M; D2d Research Group. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med 2019, 381:520-530.

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