Endogenous estrogen levels and the effects of ultra-low-dose transdermal estradiol therapy on bone turnover and BMD in postmenopausal women

J Bone Miner Res. 2007 Nov;22(11):1791-7. doi: 10.1359/jbmr.070707.


In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra-low-dose estrogen therapy on the postmenopausal skeletal health may depend critically on women's endogenous estrogen levels before treatment.

Introduction: Postmenopausal women with very low or undetectable estradiol levels have lower BMD, increased bone turnover, and increased risk of hip and vertebral fracture. We assessed whether the effects of ultra-low-dose 0.014 mg/d transdermal estradiol (Menostar; Berlex, Montvale, NJ, USA) on bone turnover and BMD are influenced by endogenous estradiol levels.

Materials and methods: We analyzed data from postmenopausal women (mean age, 66 yr) randomized to an 0.014-mg/d transdermal estradiol patch or placebo in the ultra-low-dose transdermal estrogen (ULTRA) trial. The free estradiol index (FEI), calculated as the ratio of total estradiol (by mass spectometry) to sex hormone-binding globulin (SHBG; by immunoradiometric assay) x 100, was used to estimate bioavailable estradiol at baseline. Among the 382 women who adhered to >or=80% of study medication, we examined change in serum osteocalcin and bone-specific alkaline phosphatase levels at 12 mo and total hip and lumbar spine BMD at 24 mo in each quintile of FEI.

Results: Compared with women in the highest quintile of FEI, those in the lowest quintile of FEI had a 26% greater reduction in bone-specific alkaline phosphatase and 15% greater reduction in osteocalcin in response to ultra-low estradiol treatment (p for trend across quintiles < 0.05). There was a trend toward greater improvement in total hip BMD (p = 0.06) but not spine BMD (p = 0.90) in those with lower versus higher FEI levels.

Conclusions: The beneficial effects of ultra-low-dose 0.014-mg/d transdermal estrogen therapy on skeletal health may depend critically on women's endogenous estrogen levels before treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Bone Density / drug effects*
  • Bone Remodeling / drug effects*
  • Bone and Bones / diagnostic imaging
  • Estradiol / administration & dosage*
  • Estradiol / blood
  • Estrogens / administration & dosage*
  • Estrogens / blood
  • Female
  • Humans
  • Osteoporosis, Postmenopausal / drug therapy*
  • Postmenopause
  • Radiography


  • Estrogens
  • Estradiol