The Influence of Hormonal Contraception on Vitamin D Supplementation on Serum 25(OH)D3 Status in Premenopausal Women: A Prospective Double-Blind Placebo Random Controlled Trial

Abstract

Background: A number of cross-sectional studies have highlighted a potential benefit of estrogen-containing contraception on serum 25-hydroxyvitamin D (25(OH)D) levels. The purpose of the present prospective study was to determine whether oral vitamin D3 supplementation significantly increases serum 25(OH)D more for women taking the estrogen-containing oral contraception than those not taking this medication. Methods: Thirty-eight premenopausal adult females aged 18 - 45 years old were recruited from a university campus; exclusion criteria included those presently taking vitamin D supplementation, those who stopped or started taking oral contraception in last 6 months and those taking any other form of contraception. A prospective doubleblind placebo design was implemented; the dependent variable was serum 25(OH)D and the independent variables were using or not using oral estrogen-containing contraception, and vitamin D3 or placebo supplementation. Participants were tested 4 weeks apart, and blood samples were collected using a capillary blood spot sample method and analyzed by liquid chromatography-tandem mass spectrometry. An independent technician prepared the identical supplement bottles with either 100 placebo pills or 100 active vitamin D3 pills (1,000 IU per pill) and participants randomly selected a supplement bottle. Results: Baseline measurements of 25(OH)D were non-significantly 11% higher in those taking estrogen. ANOVA results revealed a significant two-way interaction between supplementation group (treatment vs. placebo) and treatment period (before vs. after) (P < 0.001), demonstrating a substantial rise in serum 25(OH)D for the treatment group compared with the placebo group. The results also identified a three-way interaction (P = 0.014) on serum 25(OH)D between the three independent variables, with the vitamin D oral contraception group having significantly greater serum 25(OH)D increases (from 45.9 to 98.3 nmol/L) compared with those not taking oral contraception (44.2 - 69.6 nmol/L) (P = 0.019). Conclusions: The estrogen-containing oral contraception increases serum 25(OH)D in premenopausal women with a magnified effect in those taking vitamin D supplementation. Future studies need to examine the relationship between estrogen, vitamin D supplementation, serum 25(OH)D, 1,25(OH)D, parathyroid hormone and other markers of bone metabolisms.