Hormonal Contraceptive Use Is Associated With Higher Total but Unaltered Free 25-Hydroxyvitamin D Serum Concentrations

Context: Intake of hormonal contraceptives (HC) is associated with higher total 25-hydroxyvitamin D [25(OH) D] concentrations, but the effect of HC on free 25(OH) D is unclear. Objective: We investigated whether free 25(OH) D concentrations differ according to use of HC. Design: This is a post hoc analysis of a randomized open trial. Setting: This study was conducted from 13 January to 9 May, 2016, at a clinical research organization in Esslingen, Germany. Participants: We included 201 apparently healthy women of childbearing age. Intervention: Participants were randomly assigned to receive a daily multimicronutrient supplement for 8 weeks; the supplement contained 200 IU (n = 100) or 800 IU (n = 101) of vitamin D3. Main Outcome Measures: Primary outcome was the difference in free 25(OH) D between users and nonusers of HC. Results: Overall, 176 participants [median (25th to 75th percentiles) age: 25 (22 to 29) years] with available free 25(OH) D were included in the present analysis. At baseline, total 25(OH) D was significantly higher in users (n = 110) than in nonusers (n = 66) of HC [49.2 (33.4 to 63.4) vs 39.1 (23.8 to 52.5) nmol/L; P < 0.001], whereas there was no difference in free 25(OH) D [7.87 (6.50 to 10.11) vs 7.88 (6.35 to 10.12) pmol/L; P = 0.923]. These results were confirmed after multimicronutrient supplementation and in subgroups according to treatment allocation. Conclusions: Use of HC was associated with, on average, 26% higher total 25(OH) D, whereas free 25(OH) D values did not differ according to use of HC. These findings are relevant for epidemiological studies, but the physiological implications remain to be clarified.