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Transdermal estradiol patches — the same ones used to curb menopause symptoms in women — are an effective alternative to luteinizing hormone–releasing hormone agonists to lower PSA levels in men with metastatic prostate cancer, according to results from a new study.

There is also “an improvement in quality of life” compared with conventional androgen deprivation therapy (ADT), said Nicholas James, MBBS, PhD, a professor of prostate and bladder cancer research at The Royal Marsden, London, speaking at the American Society of Clinical Oncology’s 2025 Genitourinary Cancers Symposium.

“If you ask patients what bothers them about being on ADT, the things they complain about are fatigue and the hot flushes,” said James. But with estradiol patches, the hot flushes just stop.

Hypertension is also “much less of a problem, so if you’ve got somebody who’s got a cardiovascular history, it’s potentially a very attractive option,” he added.

Other advantages of estradiol patches include improved bone density, decreased fatigue, decreased sexual impact, and improved cardiovascular risk markers with no excessive thromboembolic events.

James and his colleagues randomized 79 men with metastatic prostate cancer (median age, 69 years) about equally to either standard dose luteinizing hormone–releasing hormone agonists or estradiol patches, which released 100 mcg estradiol over 24 hours.

The two treatment arms were largely balanced, but the median baseline PSA was 39 ng/mL in the patch arm vs 47 ng/mL in the luteinizing hormone–releasing hormone agonist group. Patients were also on androgen receptor pathway inhibitors during the trial, most commonly enzalutamide.

Men in the trial started out on three patches, which were changed twice a week, then dropped down to two patches once testosterone fell to castrate levels at or below 1.7 ng/mL; 91% of men on patches reached castrate levels by 12 weeks.

The main outcome measure was the proportion of men in each group who hit a PSA nadir of 0.2 ng/mL or lower by 6 months — it was identical in both groups at 61%.

As for side effects at 1 year, 54% of men in the luteinizing hormone–releasing hormone agonist group had hot flushes and 20% developed hypertension. With the estradiol patches, 18% of men had hot flushes and 5% developed hypertension.

The only drawback to the patches is a higher rate of gynecomastia (45% in the estradiol group vs 10% in the luteinizing hormone–releasing hormone agonist group), which could be bothersome to some men, James said. There was also some mild skin irritation.

The findings are in line with a larger randomized study James and his team reported at the 2024 European Society for Medical Oncology Congress. Across 1360 men with nonmetastatic prostate cancer, 3-year metastasis free survival rate was 87% in men randomized to estradiol patches vs 86% among those randomized to luteinizing hormone–releasing hormone agonists. Both groups achieved sustained castrate rates of 85%. Gynecomastia was twice as common with estradiol, but the rate of hot flushes was half that of the luteinizing hormone–releasing hormone agonist group.

In short, the approach is safe, effective, and “very cheap,” said James. “We think” estradiol patches are “a viable alternative” for ADT.

Using patches for androgen deprivation is something “honestly not a lot of us would think about,” Tyler Stewart, MD, genitourinary medical oncologist at the University of California, San Diego, told Medscape Medical News. It’s another way to significantly lower testosterone levels, “and it comes with a different side-effect profile that for some patients might be quite favourable,” he said.

James and his colleagues are now seeking a pharmaceutical partner to manufacture a single patch, so men don’t have to deal with the hassle of wearing multiple patches at once.

The work was funded by the UK Medical Research Council and others. James declared having several industry ties, including being a speaker, researcher, and/or consultant for Astellas, Pfizer, Janssen, and Merck. Stewart had no relevant disclosures. 

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.