Above the age of 50 yrs, the incidence of OA rises steeply in women but less in men, suggesting an association with changes in female hormone levels in the menopause. This systematic review summarizes the evidence on the assumed association between exogenous hormone use and OA. Medline was searched up to March 2008 for articles assessing associations between OA of hand, hip or knee and menopause-related aspects. Methodological quality of the studies was assessed systematically. The results were summarized in a best-evidence synthesis. Nineteen studies on exogenous hormone use are included. Limited evidence was seen for a protective effect of unopposed oestrogen use for incidence of hip replacement/joint replacement, and a protective trend for incident radiological OA (ROA) of the knee. In prevalence studies, conflicting evidence was observed for hormone replacement therapy (HRT) use with DIP ROA and any joint OA, and oestrogen use with clinical knee OA. We found limited evidence for a significantly increased risk by using HRT for clinical hip OA and a significant protective effect of long-term unopposed oestrogen use for hip ROA. For all other relations studied no associations were found. Heterogeneity between the hormones used and outcome measurements made statistical data pooling impossible. The assumed relationship between the exogenous hormone use and OA was not clearly observed in this review. The relationship is perhaps too complex, or other aspects, yet to be determined, play a role in the increased incidence in women aged over 50 yrs. However, there is some evidence of a protective effect of unopposed oestrogen use for hip OA.