A prospective, controlled study of the effects of hormonal contraception on bone mineral density

Obstet Gynecol. 2001 Oct;98(4):576-82. doi: 10.1016/s0029-7844(01)01495-8.


Objective: To compare the effect of depot medroxyprogesterone acetate (DMPA) and two types of oral contraceptives (OC) on bone mineral density (BMD) among women 18-33 years of age with those not using hormonal contraception.

Methods: Data from 155 women were analyzed. Depot medroxyprogesterone acetate was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone-containing pill (n = 28) or a desogestrel-containing pill (n = 35). Fifty-nine women who did not use hormonal contraception served as controls. Lumbar spine BMD was determined using dual-energy x-ray absorptiometry at baseline and after 12 months of contraceptive use. We analyzed method-related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. We had approximately 90% power to detect a 2.5% difference between any two groups.

Results: Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss (P = .01). Users of OCs generally demonstrated a gain (2.33% for norethindrone-containing pills, 0.33% for desogestrel-containing pills), which was different from controls among users of norethindrone-containing pills (P = .01), but not among users of desogestrel-containing pills (P = .99). Observed changes in BMD among DMPA users differed from women who used either type of pill (P < .002).

Conclusion: Depot medroxyprogesterone acetate has an adverse effect on BMD, in comparison with OCs or nonhormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Density / drug effects*
  • Contraceptives, Oral, Hormonal / pharmacology*
  • Delayed-Action Preparations
  • Desogestrel / pharmacology
  • Female
  • Humans
  • Lumbar Vertebrae / drug effects
  • Medroxyprogesterone Acetate / pharmacology*
  • Multivariate Analysis
  • Norethindrone / pharmacology
  • Prospective Studies


  • Contraceptives, Oral, Hormonal
  • Delayed-Action Preparations
  • Desogestrel
  • Medroxyprogesterone Acetate
  • Norethindrone