Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative

UMMS Affiliation

Meyers Primary Care Institute

Publication Date


Document Type



Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Endpoint Determination; Estrogen Replacement Therapy; Estrogens; Female; Humans; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Progestins; Proportional Hazards Models; Risk Factors; *Women's Health


Health Services Research | Primary Care | Rheumatology


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.

CONCLUSION: 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.

DOI of Published Version



Arthritis Rheum. 2006 Oct;54(10):3194-204. Link to article on publisher's site

Journal/Book/Conference Title

Arthritis and rheumatism

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PubMed ID