Estrogen Patches Match Standard Hormone Therapy for Prostate Cancer

Data from a large phase 3 clinical trial showed that transdermal estradiol patches are just as effective as the current standard hormone therapy for locally advanced prostate cancer, while significantly reducing hot flashes. The findings, published in the New England Journal of Medicine, could offer a meaningful alternative for men diagnosed with prostate cancer each year.¹

The Problem With Standard Hormone Therapy

Androgen-deprivation therapy (ADT) is the backbone of treatment for locally advanced prostate cancer. The most commonly used form involves luteinizing hormone–releasing hormone (LHRH) agonists. These are injectable drugs that suppress testosterone, the hormone that fuels prostate cancer growth.¹

Although effective, these agents markedly reduce circulating testosterone, with a secondary decline in estrogen levels. This hormonal depletion contributes to a range of adverse effects (AEs), including hot flashes, bone loss, metabolic changes, and increased cardiovascular risk. For many men, these AEs can significantly affect quality of life and treatment adherence.¹

Oral estrogen was once used as an alternative, but it fell out of favor due to an increased risk of venous thromboembolism. Transdermal estradiol (tE2), delivered via a skin patch, bypasses the digestive system and appears to reduce that risk, making it a potential alternative approach.¹

The PATCH Trial

The PATCH trial (NCT00303784)² enrolled 1360 men with locally advanced prostate cancer across 75 centers in the United Kingdom between 2007 and 2022. Participants were randomly assigned to receive either tE2 patches or LHRH agonists. The median patient age was 72, and most patients had T3-stage tumors. The primary end point was 3-year metastasis-free survival (MFS)—the proportion of patients who remained free of cancer spread after 3 years.¹

The results confirmed that tE2 was noninferior to LHRH agonists. The 3-year MFS rate was approximately 87.1% with the patch vs 85.9% with standard therapy, and the HR met the predefined noninferiority threshold. The 5-year overall survival rate also favored tE2, at 81.1% compared with 79.2%, though this difference did not reach statistical significance. Both treatments achieved castrate-level testosterone suppression in approximately 85% of patients during the first year.¹

The Safety Profile

Where the treatments differed most clearly was in their AE profiles. Hot flashes—one of the most common and distressing consequences of ADT—occurred in approximately 89% of patients receiving LHRH agonists, with 37% experiencing severe episodes. Among tE2 patients, only 44% reported hot flashes, and 8% had severe ones. That is a substantial quality-of-life difference for patients facing years of hormone therapy.¹

The trade-off was gynecomastia, or breast tissue enlargement, which occurred in 85% of tE2 patients compared with 42% of those taking LHRH agonists. Although manageable, gynecomastia is a notable cosmetic and sometimes painful AE that will require discussion between patients and clinicians.¹

What This Means for Patients

The PATCH trial gives oncologists and their patients a validated, effective alternative to LHRH agonists that may be particularly valuable for men who struggle with hot flashes or the metabolic consequences of estrogen depletion. Transdermal estradiol now has robust phase 3 evidence supporting it, and its inclusion in treatment guidelines may not be far off.

REFERENCES

1. Langley RE, Gilbert DC, Mangar S, et al; STAMPEDE-1 and PATCH Investigators. Transdermal estradiol patches in locally advanced prostate cancer. N Engl J Med. 2026;394(16):1595-1607. doi:10.1056/NEJMoa2511781

2. Prostate Adenocarcinoma TransCutaneous Hormones (PATCH). ClinicalTrials.gov. Updated November 27, 2020. Accessed April 7, 2026. https://clinicaltrials.gov/study/NCT00303784