Luteinizing hormone-releasing hormone (LH-RH) agonists or antiandrogens

In a randomized trial, the LH-RH agonist leuprolide (1 mg subcutaneously [SQ] qd) was as effective as DES (3 mg PO qd) in any T, any N, M1 patients, but caused less gynecomastia, nausea and vomiting, and thromboembolisms.[10]

In other randomized studies, the depot LH-RH agonist goserelin was as effective as orchiectomy [11,33,34] or DES at a dose of 3 mg qd.[32] A depot preparation of leuprolide, which is therapeutically equivalent to daily leuprolide, is available as a monthly or 3-monthly depot.

A systematic evidence review compared nonsteroidal antiandrogen monotherapy with surgical or medical castration from 11 randomized trials in 3,060 men with locally advanced, metastatic, or recurrent disease after local therapy.[35] Use of nonsteroidal antiandrogens as monotherapy decreased OS and increased the rate of clinical progression and treatment failure.[35][Level of evidence A1]

A small randomized study comparing 1 mg DES PO tid with 250 mg of flutamide tid in patients with metastatic prostate cancer showed similar response rates with both regimens but superior survival with DES. More cardiovascular and/or thromboembolic toxic effects of borderline statistical significance were associated with DES treatment.[36][Level of evidence A1] A variety of combinations of hormonal therapy have been tested.