Parenteral oestrogen in the treatment of prostate cancer: a systematic review

Abstract

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 Electronic databases, published paper and internet resources were searched to locate published and unpublished studies with no restriction by language or publication date.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.

Figure 1

Study identification, retrieval and inclusion.

Figure 2

Overall mortality. Trials included in the figure are those where the parenteral oestrogen was PEP alone and for which data were fully reported. It should be noted that the follow-up times reported were not entirely uniform; where data for multiple time points were available those closest to 2 years are presented. Trials with zero events in any arm are not included in the figure.

Figure 3

Overall, CVS and prostate cancer mortality at 10-year follow-up in the Mikkola trial for M0 and M1 subgroups. RRs shown are calculated from raw data presented in the publication and differ from those reported in the text, which were extracted from the Cox proportional hazards model reported.

Figure 4

CVS mortality. Trials included in the figure are those where the parenteral oestrogen was PEP alone and for which data were fully reported. It should be noted that the follow-up times reported were not entirely uniform; where data for multiple time points were available those closest to 2 years are presented. Trials with zero events in any arm are not included in the figure.

Figure 5

CVS morbidity. Trials included in the figure are those where the parenteral oestrogen was PEP alone and for which data were fully reported. It should be noted that the follow-up times reported were not entirely uniform; where data for multiple time points were available those closest to 2 years are presented. Trials with zero events in any arm are not included in the figure.