The objectives of this study were to assess the effectiveness and safety of parenteral oestrogen in the treatment of prostate cancer, and to examine any dose relationship. A systematic review was undertaken. Electronic databases, published paper and internet resources were searched to locate published and unpublished studies with no restriction by language or publication date. Studies included were randomised controlled trials of parenteral oestrogen in patients with prostate cancer; other study designs were also included to examine dose-response. Study selection, appraisal, data extraction and quality assessment were performed by one reviewer and independently checked by another. Twenty trials were included in the review. The trials differed with regard to the included patients, formulation and dose of parenteral oestrogen, comparator used, outcome measures reported and the duration of follow-up. The results provide no evidence to suggest that parenteral oestrogen, in doses sufficient to produce castrate levels of testosterone, is less effective than luteinising hormone-releasing hormone (LHRH) or orchidectomy in controlling prostate cancer, or that it is consistently associated with an increase in cardiovascular mortality. Further well-conducted trials of parenteral oestrogen are required. A pilot randomised controlled trial comparing transdermal oestrogen to LHRH analogues in men with locally advanced or metastatic prostate cancer is underway in the United Kingdom.