To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson’s disease (PD), we conducted a prospective study with 22 years of follow-up among post-menopausal participants in the Nurses’ Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of post-menopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk. The inverse relation between smoking and PD risk was attenuated among ever users of post-menopausal hormones (p for interaction = 0.05). Similar results were obtained for caffeine (p for interaction = 0.09). In exploratory analyses, women using progestin-only hormones were found to have an increased PD risk, but this result was based on a very small number of cases (n=4). In this large longitudinal study, we found no evidence of a beneficial effect of exogenous or endogenous estrogens on risk of PD. The use of post-menopausal hormone use may interact with other risk factors, but findings are preliminary and need confirmation in other populations.