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To estimate the risk of hand osteoarthritis (HOA) associated with hormone replacement therapy (HRT).; We conducted a nested case-control study using data from the UKbased Clinical Practice Research Datalink (1998-2017). In the study inception cohort comprised women at age 45. We matched women with incident HOA during follow-up (cases) to osteoarthritisfree controls on age and calendar date (index date, ID), in a ratio of 1:4. We applied conditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI) of HOA associated with new HRT use compared with non-use overall, and for women with recorded menopause we calculated separate ORs according to the time between menopause and HRT initiation (current users), and the time between HRT cessation and the ID (past users), versus non-users.; There were 3440 cases and 13,760 controls (mean age: 50.9 ± 4.1 years). We observed an adjusted OR (aOR) of HOA of 1.32 (95 % CI 1.17-1.48) in HRT users (versus nonusers), which attenuated to 0.98 (95 % CI 0.85-1.14) in women with recorded menopause. Current users (versus nonusers) who initiated HRT 3 months before or after menopause had an aOR of 0.72 (95 % CI 0.55-0.96), while aORs increased with later HRT initiation. Among past users (versus non-users), we observed an aOR of 1.25 (95 % CI 0.86-1.81) when HRT use was stopped ≤18 months before the ID, approaching the null with increasing duration between HRT cessation and the ID.; Current HRT use was associated with a decreased risk of HOA if initiated around menopause, but the risk reduction disappeared after HRT cessation.
