title: Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative.
abstract: OBJECTIVE
  To determine the effect of hormone therapy on arthroplasty rates.
  
  
  METHODS
  We examined data from the Women's Health Initiative placebo-controlled, double-blind, randomized trials. Community-dwelling women ages 50-79 years were enrolled at 40 US clinics. Women with prior arthroplasty were excluded, yielding a sample size of 26,321 subjects. Women who had had hysterectomies (n = 10,272) were randomly assigned to receive 0.625 mg/day conjugated equine estrogens (n = 5,076), or placebo (n = 5,196), with a mean followup of 7.1 years. Those who had not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean followup of 5.6 years. Participants reported hospitalizations, and arthroplasties were identified by procedure codes. Arthroplasties due to hip fracture were censored. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (95% CIs) using intent-to-treat methods and outcome of time to first procedure.
  
  
  RESULTS
  In the estrogen-alone trial, women receiving hormone therapy had significantly lower rates of any arthroplasty (HR 0.84 [95% CI 0.70-1.00], P = 0.05). However, this effect was borderline statistically significant for hip arthroplasty (HR 0.73 [95% CI 0.52-1.03], P = 0.07), and not significant for knee arthroplasty (HR 0.87 [95% CI 0.71-1.07], P = 0.19). In the estrogen-plus-progestin trial, there was no association for total arthroplasty (HR 0.99 [95% CI 0.82-1.20], P = 0.92) or for individual hip (HR 1.14 [95% CI 0.83-1.57], P = 0.41) or knee (HR 0.91 [95% CI 0.72-1.15], P = 0.41) arthroplasties.
  
  
  CONCLUSIONS
  These data suggest that hormone therapy may influence joint health, but this observed decrease in risk may be limited to unopposed estrogen and may possibly be more important in hip than in knee osteoarthritis.
authors.affiliation: University of Iowa College of Public Health, Iowa City, IA 52242, USA.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Cirillo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wallace
authors.forename: LieLing
authors.initials: L
authors.lastname: Wu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yood
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000706:statistics & numerical data*; D019645:Arthroplasty, Replacement, Knee / Q000706:statistics & numerical data*; D023381:Endpoint Determination; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000517:prevention & control / Q000601:surgery; D020370:Osteoarthritis, Knee / Q000517:prevention & control / Q000601:surgery; D011372:Progestins / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016387:Women's Health
chemical_list: D004967:Estrogens; D011372:Progestins