Managing Gynecomastia in Men Using Transdermal Estradiol

Transdermal estradiol is emerging as an alternative therapy for men experiencing adverse events from standard androgen deprivation treatments. In part 4 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, focus on concerns about the adverse events of transdermal estradiol, particularly gynecomastia, and how these concerns should be communicated to clinicians and patients. Schellhammer notes that gynecomastia and nipple or breast tenderness are often raised as immediate objections by physicians. When framed negatively—such as telling men they will “grow breasts”—this adverse event can prematurely end shared decision-making, despite potential benefits like relief from hot flashes.

Wassersug responds from both a patient and research perspective. He acknowledges experiencing mild gynecomastia himself but describes it as minimal and not bothersome. His curiosity led to a review of the literature, including studies of adult transgender women using estradiol as a comparative model. These data consistently show that breast development with estradiol is typically very limited—an A cup or less—and often insufficient for those seeking feminization, which is why many pursue implants. Wassersug emphasizes that the breast changes seen with transdermal estradiol are far smaller than what patients and physicians may imagine.

Both speakers stress the importance of education: Clinicians should describe not just the existence of gynecomastia, but its typical extent. Wassersug argues that many patients would accept mild breast development in exchange for improved sleep, cognitive function, bone protection, and reduced fracture risk. They also discuss strategies to mitigate gynecomastia, such as prophylactic external beam radiation, though data are limited, and logistical barriers reduced its effectiveness in the PATCH trial.

The use of tamoxifen is addressed and discouraged, as it may blunt estradiol’s benefits for hot flashes and bone health. Finally, Wassersug cites survey data showing that fear of estradiol adverse events was highest among patients who had never tried it, whereas those who had used estradiol reported minimal burden and often preferred it to standard androgen deprivation therapies. Both conclude that transdermal estradiol should be presented as a legitimate option, allowing informed patient choice.