Estradiol Patches in Prostate Cancer: Evidence and Impact

Work from the Estradiol Initiative highlight transdermal estradiol as a promising alternative to traditional androgen deprivation therapy (ADT) for advanced prostate cancer. In part 3 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss emerging evidence supporting transdermal estradiol as an effective and potentially superior alternative to traditional LHRH analogue ADT for advanced prostate cancer. A key barrier to adoption has been concern about survival benefit, which they address by referencing long-term data from the PATCH trial. This large study, involving more than 1600 patients since 2007, demonstrates that transdermal estradiol provides equivalent time to metastasis and overall therapeutic efficacy compared with standard LHRH-based ADT.

Schellhammer emphasizes the relevance of personalized medicine, noting that uniform dosing of injectable ADT ignores patient differences such as body mass index. Transdermal estradiol allows more individualized dosing and easy laboratory monitoring. He contrasts this with traditional ADT, which causes immediate and progressive bone loss—a silent but serious complication. Over time, this leads to significant fracture risk; STAMPEDE data show a 25% hospital admission rate for hip fractures at 10 years among men on LHRH analogues, not counting other fractures managed outside hospitals.

In contrast, estradiol therapy promotes bone preservation and even bone building from the outset, as confirmed by DEXA scans in the PATCH trial. This benefit reduces or eliminates the need for bone-protective agents such as bisphosphonates, thereby avoiding associated risks like osteonecrosis of the jaw and lowering overall health care costs.

Both speakers highlight additional quality-of-life advantages, including favorable metabolic and lipid profiles, with more data forthcoming. They also discuss compatibility with modern prostate cancer treatment strategies, including doublet and triplet therapies using second-generation anti-androgens. Preliminary evidence suggests estradiol remains safe and effective in combination regimens.

Finally, they underscore the economic implications. Transdermal estradiol may significantly reduce financial toxicity, enabling more patients to afford combination therapies that would otherwise be cost-prohibitive, while maintaining efficacy and improving long-term health outcomes.