How many women lose bone mineral density while taking hormone replacement therapy? Results from the Postmenopausal Estrogen/Progestin Interventions Trial

Arch Intern Med. 2000 Nov 13;160(20):3065-71. doi: 10.1001/archinte.160.20.3065.


Background: The frequency of bone loss among women using postmenopausal hormone therapy is unknown.

Methods: We used data from the Postmenopausal Estrogen/Progestin Interventions Trial to address the frequency of bone loss among women using postmenopausal hormone replacement therapy. Of 701 women randomized to active treatment (conjugated equine estrogens alone or in combination with 1 of 3 progestins), 538 (76.7%) were adherent and had replicate bone mineral density (BMD) measures at baseline, 12 months, and 36 months. Of 174 placebo-assigned women, 132 (75.9%) were similarly eligible. Replicate BMD measures were used to calculate within-person measurement errors, which were then used to delineate cut points that defined bone losers with 97.5%, 95.0%, 90.0%, or 75.0% confidence.

Results: At the lumbar spine, during the first 12 months, 1.5% of hormone users lost BMD with 97.5% confidence, corresponding to a decline of -3% per year; during months 12 to 36, only 0.6% of treated women lost spinal BMD to this degree. An annual loss of -1% or more was the criterion for spinal bone loss at the 75.0% confidence level; 5.1% and 8.0% of hormone users met this criterion in the first year and in months 12 to 36, respectively. For the total hip, during the first 12 months, 2.3% of hormone-adherent women lost -3.0% per year or more, the 97.5% confidence definition of loss; 0.4% were so classified during months 12 to 36. To be 75.0% confident of hip BMD loss, a -1.0% per year decline in BMD was required; using this criterion, 14.5% and 11.8% of hormone users lost total hip BMD between 0 to 12 and 12 to 36 months, respectively. Among hormone-adherent women, at the spine and hip, there was virtually no overlap between women classified as bone losers in the first 12 months and those classified as such in the last 24 months. With 95.0% certainty, corresponding to an approximate loss of -2.5% at the spine and hip, 31.3% and 11.7% of placebo-adherent women lost spinal BMD in the first 12 and last 24 months, respectively. Parallel figures for the hip were 32.3% and 7.9%, respectively.

Conclusion: Bone loss while taking postmenopausal hormones is rare, and bone loss among untreated women is far from universal.

Publication types

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

MeSH terms

  • Bone Density / drug effects*
  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Hormone Replacement Therapy*
  • Humans
  • Medroxyprogesterone Acetate / pharmacology*
  • Middle Aged
  • Progesterone Congeners / pharmacology*


  • Estrogens, Conjugated (USP)
  • Progesterone Congeners
  • Medroxyprogesterone Acetate