Design: Prospective single-arm study
Population: 38 men with biochemically recurrent prostate cancer on intermittent enzalutamide monotherapy
Primary outcome: Testosterone change and gynaecomastia
Effect: Testosterone +63% (median); gynaecomastia 42%

In a prospective US study, 38 men with biochemically recurrent prostate cancer received intermittent three-month courses of enzalutamide monotherapy without androgen deprivation.

Testosterone rose a median 63%, to a median peak of 833 ng/dL. Sixteen men (42%) developed gynaecomastia symptoms. Neither peak testosterone nor the duration of the rise correlated with gynaecomastia, and gynaecomastia in the first course did not reliably predict it in the second.

ARPI monotherapy is attractive for preserving sexual function and bone. But gynaecomastia is common enough that patients should be told before starting, and prophylaxis considered.

Warn men starting ARPI monotherapy that breast tenderness or enlargement is common.
Consider prophylactic breast-bud radiotherapy or tamoxifen where appropriate.
Do not rely on testosterone level to predict who will be affected.

Why it matters

It challenges the assumption that gynaecomastia tracks the testosterone surge.

The statistics, in plain English

With 38 men, 42% could plausibly be anywhere from about 27% to 59%. The absence of a correlation in such a small study does not rule out a modest link.