Free vitamin D does not vary through the follicular phase of the menstrual cycle

Endocrine. 2016 Jul;53(1):322-6. doi: 10.1007/s12020-016-0946-1. Epub 2016 Apr 6.


The importance of vitamin D (25OHD) in general health and reproductive success has been a focus in the setting of the 25OHD deficiency epidemic. However, there are challenges to understanding 25OHD's effects. The free and bioavailable levels are affected by 25OHD binding protein (DBP) and it is not known how estradiol fluctuations during the menstrual cycle affect these binding parameters. This may impact the most appropriate time to measure 25OHD when determining deficiency. This study characterizes 25OHD throughout the follicular phase of the menstrual cycle. Patients undergoing natural cycle IVF were included. Serum was drawn throughout the follicular phase of the menstrual cycle; 25OHD, DBP, albumin, and estrogen levels were determined for each time point allowing for mathematical calculation of free and bioavailable 25OHD. Early, mid, and late follicular phases were designated by estrogen tertiles among patients. Mean Levels of 25OHD (total, free, bioavailable) and DBP for each tertile were compared with Kruskil-Wallis test for non-parametric groups. Linear regression with GEE was employed due to repeated measures within participants. A total of 33 patients were included with 202 total serum measurements. There was no difference in mean levels of 25OHD (p = 0.77), free 25OHD (p = 0.91), and bioavailable 25OHD (p = 0.76) when measured throughout the follicular phase of the menstrual cycle. Vitamin D metabolism does not fluctuate as estradiol changes in the follicular phase of the menstrual cycle. This data indicates that assessment of 25OHD, in particular when assessed for associations with reproductive outcomes, can be measured reliably at any point during the follicular phase of the menstrual cycle.

Keywords: Bioavailable vitamin D; Menstrual cycle; Vitamin D; Vitamin D binding protein.

MeSH terms

  • Adult
  • Estrogens / blood
  • Female
  • Follicular Phase / blood*
  • Humans
  • Middle Aged
  • Serum Albumin
  • Vitamin D / blood*
  • Vitamin D-Binding Protein / blood*
  • Young Adult


  • Estrogens
  • Serum Albumin
  • Vitamin D-Binding Protein
  • Vitamin D