Methods for treating prostate cancer comprising transdermally administering a therapeutically effective amount of diethylstilbesterol (DES), or a pharmaceutically acceptable salt or complex thereof, to a subject. In one embodiment, transdermally administered DES may be used to treat hot flashes in castrate prostate cancer patients. In another embodiment, transdermal DES may be administered as a therapy while avoiding testosterone surge and clinical tumor flare (for example, for treating symptomatic locally advanced prostate cancer, treating metastatic prostate cancer, or in a subject who is contraindicated for conventional therapy such as ADT therapy, particularly GnRH (gonadotropin-releasing hormone) therapy). In a further embodiment, transdermal DES may be administered to treat osteoporosis in men with prostate cancer. The transdermal DES may be used as a front line hormonal therapy or a second line hormonal therapy for treating prostate cancer.