Reproductive history and osteoarthritis in the Women's Health Initiative

Objective: To investigate the relationship between self-reported osteoarthritis (OA) and reproductive factors in the Women's Health Initiative (WHI). Method: We used multivariable logistic regression to study the association of self-reported OA and reproductive factors in the WHI Observational Study and Clinical Trial cohorts of 145 965 postmenopausal women, in a retrospective cross-sectional format. Results: In our cohort, we observed no clinically significant associations between reproductive factors and OA given small effect sizes. The following factors were associated with statistically significant increased likelihood of developing OA: younger age at menarche (p < 0.001), history of hysterectomy [adjusted odds ratio (aOR) 1.013, 95% confidence interval (CI) 1.004-1.022, p = 0.04 vs no hysterectomy], history of unilateral oophorectomy (aOR 1.015, 95% CI 1.004-1.026, p < 0.01 vs no oophorectomy), parity (aOR 1.017, 95% CI 1.009-1.026, p < 0.001), ever use of oral contraceptives (aOR 1.008, 95% CI 1.001-1.016, p < 0.01 vs never use), and current use of hormonal therapy (reference current users, aOR 0.951, 95% CI 0.943-0.959 for never users; aOR 0.981, 95% CI 0.972-0.989 for past users; global p < 0.001). Age at menopause, first birth, and pregnancy were not associated with OA. Among parous women, no clear pattern was observed with number of pregnancies, births, or duration of breastfeeding in relation to OA. Conclusion: Our study showed that reproductive factors did not have significant clinical associations with OA after controlling for confounders. This may be due to complex hormonal effects. Additional investigation is warranted in prospective cohort studies. The Women's Health Initiative is registered under ClinicalTrials.gov. Trial registration ID: NCT00000611.