Cardiovascular Events With Transdermal Estradiol vs LHRH Agonists for Androgen Suppression in Advanced Prostate Cancer

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In an analysis from the UK phase II/III PATCH trial reported in The Lancet, Langley et al found no differences in cardiovascular event rates over long-term follow-up with the use of a transdermal estradiol patch vs luteinizing hormone-releasing hormone agonists (LHRHa) for androgen suppression in patients with advanced prostate cancer.

Study Details

In the multicenter trial, 1,694 men with locally advanced or metastatic disease were randomly assigned (244 in 1:2 design, remainder in 1:1 design) between August 2007 and July 2019 to receive LHRHa according to local practice (n = 790) or transdermal estradiol patches (n = 904). Patch treatment consisted of four 100-μg patches per 24 hours, changed twice weekly, with a reduction to three patches twice weekly if castration was achieved at 4 weeks (testosterone ≤ 1.7 nmol/L).

Patients with disease progression on transdermal estradiol patches were permitted to switch to LHRHa. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory postmortem report was available, and as other relevant events if no postmortem report was available.

The primary endpoints of the ongoing trial are overall and progression-free survival.

Key Findings

Median follow-up was 3.9 years (interquartile range = 2.4–7.0 years). Castration rates at 1 and 3 months were 83% and 93% among patients in the transdermal estradiol group and 65% and 93% among those in the LHRHa group.  

A total of 157 cardiovascular events in 145 men met the predefined event criteria. An additional 10 sudden deaths with no postmortem report were observed (total of 167 events in 153 men). Fatal cardiovascular events occurred in 11 patients (1%) in the transdermal estradiol group vs 26 (2%) in the LHRHa group.

Overall, cardiovascular events occurred in 89 patients (10%) in the transdermal estradiol group and 64 (8%) in the LHRHa group. A total of 30 (34%) of 89 cardiovascular events in the transdermal estradiol group occurred more than 3 months after patients stopped transdermal estradiol or switched to LHRHa. Overall, rates of cardiovascular events or sudden death without postmortem report at 12, 24, and 36 months were 2.8% vs 2.8%, 6.4% vs 5.3%, and 8.0% vs 7.2%.

No significant differences in time to first cardiovascular event between the transdermal estradiol vs LHRHa groups were observed, whether analysis included sudden deaths without postmortem report (hazard ratio [HR] = 1.11, 95% confidence interval [CI] = 0.80–1.53, P = .54) or only confirmed events (HR = 1.20, 95% CI = 0.86–1.68, P = .29).

The most common adverse events of any grade were gynecomastia, occurring in 86% of the transdermal estradiol group vs 38% of the LHRHa group (P < .0001), and hot flushes, occurring in 35% vs 86% (P < .0001).

The investigators concluded, “Long-term data comparing transdermal estradiol patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Estrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer.”

Ruth E. Langley, PhD, of the MRC Clinical Trials Unit at University College London, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Cancer Research UK and Medical Research Council Clinical Trials Unit at University College London. For full disclosures of the study authors, visit