title: Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover.
abstract: BACKGROUND
  The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF).
  
  
  METHODS
  In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4-week cycles of pSSR (transdermal oestradiol, 100 μg daily for week 1, 150 μg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 μg and 1·5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12-month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment.
  
  
  RESULTS
  Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z-score was -0·89 (95% CI -1·27 to -0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI -0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = -0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001).
  
  
  CONCLUSIONS
  We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.
authors.affiliation: Department of Paediatric Biochemistry, The Royal Hospital for Sick Children, Edinburgh, Scotland, UK.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Crofton
authors.forename: Nancy
authors.initials: N
authors.lastname: Evans
authors.forename: Louise E
authors.initials: LE
authors.lastname: Bath
authors.forename: Pamela
authors.initials: P
authors.lastname: Warner
authors.forename: Tessa J
authors.initials: TJ
authors.lastname: Whitehead
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Kelnar
authors.forename: W Hamish B
authors.initials: WH
authors.lastname: Wallace
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage / Q000627:therapeutic use; D016649:Primary Ovarian Insufficiency / Q000188:drug therapy* / Q000378:metabolism*; D011374:Progesterone / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D009640:Norethindrone