title: The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications.
abstract: Data are presented showing that human prostatic adenocarcinoma depends on dihydrotestosterone (DHT) and not testosterone (T) for growth. It follows that androgen ablative therapy should be directed toward elimination of DHT with retention of circulating T. This can be achieved by using a 5 alpha-reductase inhibitor such as 6-methyleneprogesterone (6-MP) (VII). Arguments are presented showing that 6-MP (VII) is expected 1) to function as a prophylactic agent against prostate cancer, 2) to represent an attractive therapeutic modality for palliative treatment of the hormone-responsive disease, and 3) to be compatible with other therapeutic modalities when very low prostatic levels of DHT should be within reach.
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000230:Adenocarcinoma / Q000209:etiology* / Q000628:therapy; D000818:Animals; D013196:Dihydrotestosterone / Q000502:physiology*; D006801:Humans; D008297:Male; D009374:Neoplasms, Experimental / Q000209:etiology; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology* / Q000628:therapy; D011374:Progesterone / Q000031:analogs & derivatives / Q000627:therapeutic use; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000628:therapy; D051381:Rats; D013739:Testosterone / Q000502:physiology
chemical_list: D058891:5-alpha Reductase Inhibitors; D013196:Dihydrotestosterone; C036790:6-methylene-4-pregnene-3,20-dione; D013739:Testosterone; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase