Effects of hormonal contraception on bone mineral density after 24 months of use

Obstet Gynecol. 2004 May;103(5 Pt 1):899-906. doi: 10.1097/01.AOG.0000117082.49490.d5.


Objective: To measure the effect of 24 months of depot medroxyprogesterone acetate use on bone mineral density compared with oral contraception (pills) and nonhormonal contraception.

Methods: Women aged 18-33 years self-selected oral contraception, depot medroxyprogesterone acetate, or nonhormonal contraception (controls). Those selecting pills were randomized to formulations containing either 35 microg ethinyl estradiol and norethindrone or 30 microg ethinyl estradiol and desogestrel. Controls were frequency matched on age and race/ethnicity to hormonal contraception users. Dual-energy X-ray absorptiometry of the lumbar spine (L1-L4) was performed at baseline, 12 months, and 24 months. Percent change in bone mineral density was analyzed by using analysis of covariance, adjusting for age, race/ethnicity, weight-bearing exercise, calcium intake, smoking status, and body mass index.

Results: Of the 191 women making up the final sample, 86 used pills, 47 used depot medroxyprogesterone acetate, and 58 used nonhormonal contraception. Women using depot medroxyprogesterone acetate for 24 months experienced, on average, a 5.7% loss in bone mineral density, with a 3.2% loss occurring between months 12 and 24. On average, users of desogestrel pills experienced a 2.6% loss in bone mineral density after 24 months. Bonferroni-adjusted pairwise comparisons demonstrated that bone mineral density changes from baseline to 24 months among depot medroxyprogesterone acetate users differed significantly from changes experienced by either of the pill groups or the control group. Changes in bone mineral density among users of either pill did not significantly differ from each other or from controls.

Conclusion: Loss of bone mineral density associated with depot medroxyprogesterone acetate use appears to be linear during the first 2 years of use. Shifts in bone mineral density among pill users were not significant when compared with controls.

Publication types

  • 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*
  • Contraceptive Agents, Female / pharmacology*
  • Contraceptives, Oral, Hormonal / pharmacology*
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Delayed-Action Preparations
  • Desogestrel / pharmacology*
  • Estrogens / pharmacology*
  • Ethinyl Estradiol / pharmacology*
  • Female
  • Humans
  • Medroxyprogesterone Acetate / pharmacology*
  • Norethindrone / pharmacology*
  • Time Factors


  • Contraceptive Agents, Female
  • Contraceptives, Oral, Hormonal
  • Contraceptives, Oral, Synthetic
  • Delayed-Action Preparations
  • Estrogens
  • Ethinyl Estradiol
  • Desogestrel
  • Medroxyprogesterone Acetate
  • Norethindrone