Estrogen and other female reproductive risk factors are not strongly associated with the development of rheumatoid arthritis in elderly women

Semin Arthritis Rheum. 2003 Oct;33(2):72-82. doi: 10.1016/s0049-0172(03)00084-2.


Objective: Endogenous and exogenous reproductive hormones have been associated with rheumatoid arthritis (RA) in women, but data are inconsistent and no studies have assessed RA risk factors exclusively in elderly women.

Methods: The authors examined the association between reproductive factors, exogenous hormone exposure, and RA in a prospective cohort study of 31,336 Iowa women who were aged 55 to 69 years at cohort baseline in 1986.

Results: During 11 years of follow-up, 158 incident cases of RA were identified and validated. Age at last pregnancy (P trend =.01) and age at menopause (P trend =.03) were inversely associated with RA, whereas a history of polycystic ovary syndrome (relative risk [RR], 2.58; 95% confidence interval [CI], 1.06 to 6.30), endometriosis (RR, 1.72; 95% CI, 0.93 to 3.18), and former use of hormone replacement therapy (RR, 1.47; 95% CI, 1.04 to 2.06) were positively associated with RA. In multivariate analysis models, a history of polycystic ovary syndrome remained the most consistent predictor of RA, whereas the RRs for other factors attenuated.

Conclusion: Few reproductive factors showed a strong or statistically significant association with RA in elderly women. The association of polycystic ovary syndrome may be indicative of perturbations of endocrine-immune activity that may influence the development of RA. This prospective cohort study adds to the understanding of the potential contribution of hormonal factors to the cause of RA in older women.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / etiology*
  • Contraceptives, Oral, Hormonal / immunology*
  • Contraceptives, Oral, Hormonal / pharmacology
  • Estrogen Replacement Therapy / methods
  • Estrogens / immunology*
  • Estrogens / pharmacology
  • Female
  • Humans
  • Middle Aged
  • Prospective Studies
  • Reproductive History*
  • Risk Factors
  • Sex Factors


  • Contraceptives, Oral, Hormonal
  • Estrogens