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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.