The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D

Buchanan, J.R.; Santen, Richard J.; Cauffman, Susanne W.; Cavaliere, A; Greer, Robert B.; Demers, Laurence M.

doi:10.1007/bf02555109

Cited by 58 publications

(36 citation statements)

References 26 publications

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“…The pathogenesis of AIMSS and why it may respond to vitamin D is unclear. One hypothesis is that estrogen deficiency causes a reduction in the activity of 1-alphahydroxylase, the enzyme that catalyzes the hydroxylation of calcidiol (25(OH)D) to calcitriol (1-25(OH) 2 D) [37]. Moreover, AI therapy may increase the requirements of vitamin D through competition with hepatic CYP3A4 [38,39].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial

Rastelli

Taylor

Gao

et al. 2011

Breast Cancer Res Treat

108

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A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20-29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10-19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baseline musculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.

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Section: Discussionmentioning

confidence: 99%

Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial

Rastelli

Taylor

Gao

et al. 2011

Breast Cancer Res Treat

108

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“…An increase in total 1,25(OH) 2 D (13, 14) has been reported, though others found no such effect (15). Most, but not all (14), studies report an increase in the concentration of DBP (2,13). Two studies report no change in the free 1,25(OH) 2 D index during oral estrogen intake (8,13), but the actual free concentration was not assessed.…”

Section: Discussionmentioning

confidence: 99%

“…An increase in total 1,25(OH) 2 D has been found (8,13,14), but also no increase (15). Only two studies investigated the free index and found it to remain constant (8,13).…”

Section: Introductionmentioning

confidence: 99%

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Hoof¹,

Sévaux

Baelen

et al. 2001

European Journal of Endocrinology

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Objective: A novel assay was employed to study the free 1,25-dihydroxyvitamin D (1,25(OH) 2 D) concentrations in various populations with different levels of 1,25(OH) 2 D and vitamin D binding protein (DBP). Design: In 12 healthy women before and after 3 months of oral estrogen/progestagen treatment, 10 pregnant women, and 16 patients with a nephrotic syndrome and normal renal function, the concentrations of total and free 1,25(OH) 2 D, DBP and albumin were assessed. Methods: The total concentration of 1,25(OH) 2 D in serum was assessed using a radioreceptor assay. The free fraction of 1,25(OH) 2 D was measured using symmetric dialysis. DBP was assessed using single radial immunodiffusion. Serum albumin concentrations were measured on an automated analyzer. Results: In healthy women, the concentrations of total 1,25(OH) 2 D, free 1,25(OH) 2 D and DBP were 132^19 pmolalY 92^30 fmolal and 5X59^0X43 mmolalX After 3 months of estrogen/progestagen treatment, total 1,25(OH) 2 D and DBP levels rose significantly to 175^51 pmolal and 8X321 X59 mmolal P # 0X05 and P # 0X001; the free 1,25(OH) 2 D remained unchanged 1053 9 fmolal; not significant). Pregnant women had significantly higher levels of total 1,25(OH) 2 D and DBP 239^68 pmolal and 11X32^1X77 mmolal; both P # 0X001; the free 1,25(OH) 2 D level, however, was not different 104^27 fmolal; not significant). Unexpectedly, in patients with nephrotic syndrome, no lower DBP levels were found 5X36^0X84 mmolal relative to that in controls. Despite this, levels of both total 69^26 pmolalY P # 0X001 and free 1,25(OH) 2 D 532 8 fmolal; P # 0X001 were significantly lower than in controls. Albumin levels were lowered from 628^38 mmolal to 300^84 mmolal (P # 0.001). Conclusions: Higher estrogen levels result in higher DBP levels, with a parallel rise in total 1,25(OH) 2 D levels but without a change in the biologically active free fraction. The results in patients with nephrotic syndrome show that, with increasing glomerular protein leakage, the free 1,25(OH) 2 D concentration cannot be maintained.

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“…the VDR and vitamin D binding protein, which is the main vitamin D metabolite carrier in the circulation. 22,40,41 Estrogen also appears to downregulate vitamin D 24-hydroxylase, the main catabolic enzyme in the vitamin D pathway. 22,42 Together, these actions may result in elevated circulating vitamin D metabolites, although the clinical significance of this effect remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Positive Association Between 25-Hydroxyvitamin D and C-Reactive Protein is Confounded by Hormonal Contraceptive Use

García‐Bailo

Josse

Jamnik

et al. 2013

Journal of Women's Health

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The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D

Cited by 58 publications

References 26 publications

Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial

Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Positive Association Between 25-Hydroxyvitamin D and C-Reactive Protein is Confounded by Hormonal Contraceptive Use

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