Estradiol patches match standard hormone injections
In men with locally advanced prostate cancer, estradiol skin patches were as effective as standard hormone injections for preventing spread or death at 3 years, with fewer hot flashes but more breast swelling.
*Randomized noninferiority trial; Level 1b (OCEBM).

Citation

Langley RE, Gilbert DC, Mangar S, et al. Transdermal Estradiol Patches in Locally Advanced Prostate Cancer. N Engl J Med. 2026;394:1595-1607. doi:10.1056/NEJMoa2511781.

Background

Standard hormone-suppressing injections lower testosterone but also lower estrogen, contributing to hot flashes and bone loss. Estradiol delivered through the skin may suppress testosterone while avoiding some estrogen-depletion symptoms.

Patients

1360 men (median age 72) in the United Kingdom with locally advanced, non-metastatic prostate cancer (no distant spread; lymph nodes negative or positive). Excluded: clinically significant prior heart or blood-vessel disease, or unfit for trial treatments.

Intervention

Estradiol skin patches (100 micrograms per 24 hours; dose adjusted after 4 weeks).

Control

Luteinizing hormone–releasing hormone agonist injections (every 4 or 12 weeks).

Outcome

Primary: 3-year metastasis-free survival (no confirmed distant spread or death). Secondary: testosterone suppression, overall survival, side effects.

Follow-up Period

Primary outcome at 3 years; overall survival reported at 5 years.

Results

Estradiol patches met the prespecified “not worse than” criterion for 3-year metastasis-free survival: 87.1% with patches vs 85.9% with injections (risk over time ratio 0.96; one-sided 95% upper limit 1.11). Primary analysis was intention-to-treat.
Outcome (during treatment) Estradiol patches Hormone injections Absolute difference NNT/NNH
Hot flashes (any) 44% 89% -45% NNT 3 (fewer hot flashes)
Hot flashes (moderate or worse) 8% 37% -29% NNT 4
Breast swelling (any) 85% 42% +43% NNH 3 (more breast swelling)
Breast swelling (moderate or worse) 37% 9% +28% NNH 4

Limitations

Open-label design. Usual care changed over the long recruitment period (for example, more use of prostate radiation and chemotherapy). Men with significant cardiovascular disease were excluded, limiting generalizability. Some men switched off patches earlier, which could affect longer-term comparisons.

Funding

Cancer Research U.K. and the U.K. Medical Research Council.

Clinical Application

For eligible men without major cardiovascular disease, discuss estradiol patches as an alternative to standard injections, especially when avoiding hot flashes is a priority.