Effect of hormonal contraceptives on vitamin B12 level and the association of the latter with bone mineral density

Contraception. 2012 Nov;86(5):481-7. doi: 10.1016/j.contraception.2012.02.015. Epub 2012 Mar 28.


Background: The study was conducted to estimate the effect of depot medroxyprogesterone acetate (DMPA) and oral contraceptives (OC) containing 20 mcg ethinyl estradiol on serum B12 and whether observed changes impact bone mineral density (BMD).

Study design: Serum B12 and BMD at the lumbar spine and femoral neck were measured on 703 women using OC, DMPA or nonhormonal (NH) birth control at baseline and every 6 months thereafter for 3 years.

Results: OC and DMPA users experienced greater decreases in B12 than NH users (p<.001). A sharp decrease in B12 was observed during the first 6 months of hormonal contraceptive use (OC: 97 pg/mL and DMPA: 64 pg/mL) in contrast to 14 pg/mL among NH users (20%, 13% and 3% of their baseline values, respectively). Over the following 30 months, B12 levels of OC users remained almost flat, while DMPA users had a further 22-unit decrease. Very few women demonstrated B12 deficiency. Moreover, B12 levels were not associated with BMD.

Conclusion: Hormonal contraception causes B12 levels to decrease, but this does not appear to be clinically significant or affect BMD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Bone Density* / drug effects
  • Contraceptives, Oral, Hormonal / adverse effects*
  • Ethinyl Estradiol / adverse effects
  • Female
  • Femur Neck
  • Humans
  • Longitudinal Studies
  • Lumbar Vertebrae
  • Medroxyprogesterone Acetate / adverse effects
  • Vitamin B 12 / blood*
  • Vitamin B 12 Deficiency / chemically induced
  • Vitamin B 12 Deficiency / complications


  • Contraceptives, Oral, Hormonal
  • Ethinyl Estradiol
  • Medroxyprogesterone Acetate
  • Vitamin B 12