title: Prevention of postmenopausal bone loss with long-cycle hormone replacement therapy.
abstract: OBJECTIVE
  Postmenopausal bone loss and osteoporotic fractures can be prevented by hormone replacement therapy (HRT). However, opposed HRT may increase the risk of breast cancer above that associated with estrogen alone and in non-hysterectomized women estrogen substitution alone increases the risk of uterine cancer, which triggered renewed interest in long-cycle HRT regimens (estrogen replacement therapy with progesterone-free intervals up to 6 months). The effects on bone of such long-cycle HRT regimens are unknown. The objective of the present study was to compare the effects on bone and the endometrium of long-cycle HRT and conventional HRT.
  
  
  METHODS
  Seventy-three healthy non-hysterectomized postmenopausal women were randomized to either conventional HRT (estradiol (E2) 2 mg/d during 12 days, E2 2 mg/d plus 1 mg/d of norethisterone acetate (NETA) during 10 days, E2 1 mg/d for 6 days) or long-cycle HRT treatment (two cycles with E2 2 mg/d during 28 days, followed by one cycle of conventional HRT and repeated every 3 months). Primary endpoint was the change in bone mineral density (BMD) at the lumbar spine (LS) over 24 months.
  
  
  RESULTS
  BMD at LS increased significantly versus baseline in both treatment groups (conventional HRT +3.8 +/- 0.6%, long-cycle HRT +3.3 +/- 0.5%, p < 0.0001 for both) with no significant difference between treatment groups over 24 months. Similar significant BMD increases versus baseline were observed at the femoral neck, while biochemical markers of bone turnover (osteocalcin and deoxypyridinoline) were significantly decreased over 24 months. There were no endometrial or breast related adverse events reported.
  
  
  CONCLUSIONS
  Long-cycle HRT may be a valid alternative to conventional HRT with regard to protection against postmenopausal bone loss.
authors.affiliation: Osteoporosis Policlinic, University Hospital of Berne, Switzerland.
authors.forename: Albrecht W E
authors.initials: AW
authors.lastname: Popp
authors.forename: Christine
authors.initials: C
authors.lastname: Bodmer
authors.forename: Christoph
authors.initials: C
authors.lastname: Senn
authors.forename: Gaby
authors.initials: G
authors.lastname: Fuchs
authors.forename: Marius E
authors.initials: ME
authors.lastname: Kraenzlin
authors.forename: H
authors.initials: H
authors.lastname: Wyss
authors.forename: Martin H
authors.initials: MH
authors.lastname: Birkhaeuser
authors.forename: Kurt
authors.initials: K
authors.lastname: Lippuner
mesh_terms: D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects*; D004714:Endometrial Hyperplasia / Q000139:chemically induced; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000517:prevention & control*; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone