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

J Clin Endocrinol Metab. 2018 Jun 1;103(6):2385-2391. doi: 10.1210/jc.2018-00336.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cholecalciferol / administration & dosage*
  • Contraceptives, Oral, Hormonal / therapeutic use*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Young Adult


  • Contraceptives, Oral, Hormonal
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D

Associated data

  • DRKS/DRKS00009770