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 Electronic databases, published paper and internet resources were searched to locate published and unpublished studies with no restriction by language or publication date.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

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

“…The trials differed with regard to the included patients, formulation and dose of parenteral estrogen, comparator used, outcome measures reported, and the duration of follow-up. The results provide no evidence to suggest that parenteral estrogen is consistently associated with an increase in cardiovascular mortality compare with orchidectomy or LHRHa (34).…”

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

“…Overall experience with the therapeutic use of estrogens in PCa does not suggest a clinically important pro-carcinogenic effect. A systematic review of 20 RCTs of the use of high-dose parenteral E 2 as ADT for locally advanced or metastatic PCa found no evidence that E 2 treatment differed in efficacy from LHRHa or orchiectomy when comparing overall mortality (Norman et al 2008). Oncologic outcomes from the PATCH study are yet to be reported (Langley et al 2013).…”

“…For symptomatic breast enlargement requiring intervention, the proportions were 9% and 0%, respectively. Pre-treatment breast irradiation, given as a single dose, has efficacy in preventing gynaecomastia and was part of older protocols for oral DES (Beck et al 1978) and intramuscular PEP (Norman et al 2008). In SPCG-5, 240 mg intramuscular PEP per month over 11 years caused gynaecomastia in the majority of patients: 60% of those who received prophylactic breast irradiation and 84% of those who did not (by comparison, 48% of irradiated and 36% non-irradiated patients in the CAB group) (Hedlund et al 2008).…”

“…Earlier studies of high-dose estrogen therapy do not provide useful information because the aim of this therapy was to achieve medical castration, not to achieve physiologic E 2 levels, and E 2 levels were generally not reported. When parenteral E 2 is used to achieve medical castration, a dose of at least 240 mg of E 2 per month is required (Norman et al 2008).…”

Systemic Therapies for Non-Metastatic Prostate Cancer: Review of the Literature

“…Interestingly,arecentsystematicreviewprovidednoevidence that parenteral estrogen, in doses sufficient to produce castrate levels of testosterone, is less effective than LHRH or orchidectomyincontrollingprostatecancer,orthatitisconsistently associated with an increase in cardiovascular mortality [8].Somestudiesinvestigatedtheroleofantiandrogen monotherapy in non-metastatic prostate cancer [9][10]. The analysisoftherandomizedEarlyProstateCancerPrograminvestigatingtheadditionofbicalutamide,150mg,tostandard careforlocalizedorlocallyadvancednon-metastaticprostate cancer(medianfollow-up7.4years)hasshownthatantiandrogendoesnotbenefitpatientswithlocalizeddiseasebutdoes confersignificantprogression-freesurvivalbenefitsinlocally advanced disease, irrespective of the standard care received (radicalprostatectomy,RT,orwatchfulwaiting) [9].…”