title: The dose-response of percutaneous oestradiol implants on the skeletons of postmenopausal women.
abstract: OBJECTIVE
  To determine whether there is a dose-response effect of percutaneous oestradiol implants on the skeletons of postmenopausal women using a range of doses available in clinical practice.
  
  
  METHODS
  One year randomised study.
  
  
  METHODS
  Forty-five postmenopausal women who requested oestrogen replacement therapy were randomised to receive 25 mg, 50 mg, or 75 mg oestradiol implants. The bone mineral density changes were compared with a control group of 15 untreated women.
  
  
  METHODS
  Dual energy X-ray absorptiometry using Hologic 1000 QDR before treatment and after one year of treatment. Plasma oestradiol and follicle stimulating hormone levels before treatment and after one year.
  
  
  RESULTS
  There were significant correlations between the plasma oestradiol levels and the percentage increase in bone density at the lumbar spine, the total hip, the femoral neck, and the trochanter. The median (range) plasma oestradiol level was 327 pmol/l (114-853) in the 25 mg group, 358 pmol/l (220-957) in the 50 mg group and 518 pmol/l (167-828) in the 75 mg group. Three women who lost a significant amount of bone from the clinically relevant sites in the 25 mg oestradiol group all had plasma oestradiol levels below 300 pmol/l. None of the women in either the 50 mg or 75 mg oestradiol groups lost bone from these sites.
  
  
  CONCLUSIONS
  Oestradiol implants resulted in a wide range of circulating oestradiol levels with each of the doses used. There was a significant relation between plasma oestradiol levels and the increases in bone density at both the lumbar spine and the proximal femur. None of the women lost bone density at the clinically important sites of the spine and femoral neck if their plasma oestradiol levels were above 300 pmol/l.
authors.affiliation: Department of Gynaecology, Chelsea and Westminster Hospital, London, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Studd
authors.forename: E F
authors.initials: EF
authors.lastname: Holland
authors.forename: A T
authors.initials: AT
authors.lastname: Leather
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005269:Femur / Q000502:physiology; D005272:Femur Neck / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000097:blood; D006621:Hip Joint / Q000502:physiology; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000502:physiology*
chemical_list: D004343:Drug Implants; D004958:Estradiol; D005640:Follicle Stimulating Hormone