Breast tenderness is a common and usually benign side effect of HRT because... Breast tenderness is one of the most common side effects of Hormone Replacement Therapy, pretty much irregardless of which formulation you use. Breast tissue responds to estrogens and progestins. In many cases, tenderness is temporary as the tissues sort of “wake up” when they are exposed to these hormones after having been without them for a while. Tenderness may also be helped by ensuring that your diet has adequate