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      100 YEARS OF VITAMIN D: Combined hormonal contraceptives and vitamin D metabolism in adolescent girls

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          Abstract

          Objective

          Combined hormonal contraceptive (CHC) use has been associated with higher total 25-hydroxyvitamin D (25(OH)D) levels. Here, we investigate the relation between CHC use and vitamin D metabolism to elucidate its clinical interpretation.

          Methods

          The cross-sectional Fit Futures 1 included 1038 adolescents. Here, a subgroup of 182 girls with available 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH) 2D), 24,25-dihydroxyvitamin D (24,25(OH) 2D), vitamin D-binding protein (DBP) and measured free 25(OH)D levels, in addition to parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), was investigated. Vitamin D metabolites were compared between girls using (CHC+) and not using CHC (CHC−). Further, the predictability of CHC on 25(OH)D levels was assessed in a multiple regression model including lifestyle factors. The ratios 1,25(OH) 2D/25(OH)D and 24,25(OH) 2D/25(OH)D (vitamin D metabolite ratio (VMR)) in relation to 25(OH)D were presented in scatterplots.

          Results

          CHC+ ( n  = 64; 35% of the girls) had higher 25(OH)D levels (mean ± s.d., 60.3 ± 22.2) nmol/L) than CHC- ( n  = 118; 41.8 ± 19.3 nmol/L), P -values <0.01. The differences in 25(OH)D levels between CHC+ and CHC− were attenuated but remained significant after the adjustment of lifestyle factors. CHC+ also had higher levels of 1,25(OH) 2D, 24,25(OH) 2D, DBP and calcium than CHC−, whereas 1,25(OH) 2D/25(OH)D, PTH, FGF23 and albumin were significantly lower. Free 25(OH)D and VMR did not statistically differ, and both ratios appeared similar in relation to 25(OH)D, irrespective of CHC status.

          Conclusion

          This confirms a clinical impact of CHC on vitamin D levels in adolescents. Our observations are likely due to an increased DBP-concentration, whereas the free 25(OH)D appears unaltered.

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          Most cited references38

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          Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

          The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
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            Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein.

            We measured the free fraction of 25-hydroxyvitamin D (25OHD) in human serum and determined that 25OHD bound to a component with an affinity constant of 7 X 10(8) M-1 and a concentration of 4.5 X 10(-6) M. This concentration was equal to that of the vitamin D-binding protein (DBP) in the same serum sample. We removed DBP from the serum using actin affinity columns and found that the affinity for 25OHD of the remaining serum components was equivalent to that of human serum albumin (6 X 10(5) M-1). We then measured the free fractions of 25OHD, DBP, and albumin in normal and cirrhotic subjects. We calculated that 88 +/- 3% (+/- SD) and 83 +/- 8% of the 25OHD were bound to DBP in the serum of normal and cirrhotic subjects, respectively. We compared previously reported data for the free fraction and the free concentration of 1,25-dihydroxyvitamin D in these subjects with the current data for the free fraction and free concentration of 25OHD. The total concentrations and free fractions of both metabolites correlated to each other and to the DBP and albumin concentrations in these subjects, but the free concentrations of these metabolites did not. We conclude that 25OHD, like 1,25-dihydroxyvitamin D, is transported in blood bound primarily to DBP and albumin. Changes in the concentrations of DBP and albumin affected the total and free fractions of 25OHD in serum, but the actual free concentration of 25OHD was independent of such changes.
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              Consensus statement from 2 nd International Conference on Controversies in Vitamin D

              The 2nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) “Laboratory”: assays and threshold values to define vitamin D status; 2) “Clinical”: sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) “Therapeutics”: controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                25 February 2022
                01 March 2022
                : 11
                : 3
                : e210395
                Affiliations
                [1 ]Tromso Endocrine Research Group , Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway
                [2 ]Diagnostic Clinic , University Hospital of North Norway, Tromso, Norway
                [3 ]Hormone Laboratory , Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway
                [4 ]Division of Neurosciences , Orthopedics and Rehabilitation Services, University Hospital of North Norway, Tromso, Norway
                [5 ]Division of Internal Medicine , University Hospital of North Norway, Tromso, Norway
                Author notes
                Correspondence should be addressed to J Öberg: Johanna.oberg@ 123456uit.no

                This paper forms part of a special series on 100 Years of Vitamin D. The guest editors for this section were Josef Köhrle, Susan Lanham-New and Martina Rauner

                Author information
                http://orcid.org/0000-0001-8828-8181
                Article
                EC-21-0395
                10.1530/EC-21-0395
                9002185
                35213326
                670928da-b2e7-4360-9ecc-ff43466ac57b
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 15 February 2022
                : 25 February 2022
                Categories
                Research

                vitamin d,adolescence,combined hormonal contraceptive,metabolite ratio,free 25-hydroxyvitamin d,impact of vitamin d binding protein

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