title: Endogenous estrogen levels and the effects of ultra-low-dose transdermal estradiol therapy on bone turnover and BMD in postmenopausal women.
abstract: 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.
  
  
  BACKGROUND
  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.
  
  
  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.
authors.affiliation: Veterans Affairs Medical Center, San Francisco, California, USA. ahuang@ucsfmed.org
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Huang
authors.forename: Bruce
authors.initials: B
authors.lastname: Ettinger
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D004967:Estrogens / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause; D011859:Radiography
chemical_list: D004967:Estrogens; D004958:Estradiol