Diethylstilbestrol (DES) acting as an estrogen at the level of the hypothalamus to downregulate hypothalamic luteinizing hormone (LH) production results in decreased elaboration of testosterone by the testicle. For this reason, orchiectomy is equally as effective as moderate-dose DES, inducing responses in 80% of previously untreated patients with prostate cancer but without the prominent cardiovascular side effects of DES, including thrombosis and exacerbation of coronary artery disease. In the event that orchiectomy is not accepted by the patient, testicular androgen suppression can also be effected by luteinizing hormone–releasing hormone (LHRH) agonists such as leuprolide and goserelin. . | Chapter 081. Principles of Cancer Treatment Part 17 Prostate cancer is classically treated by androgen deprivation. Diethylstilbestrol DES acting as an estrogen at the level of the hypothalamus to downregulate hypothalamic luteinizing hormone LH production results in decreased elaboration of testosterone by the testicle. For this reason orchiectomy is equally as effective as moderate-dose DES inducing responses in 80 of previously untreated patients with prostate cancer but without the prominent cardiovascular side effects of DES including thrombosis and exacerbation of coronary artery disease. In the event that orchiectomy is not accepted by the patient testicular androgen suppression can also be effected by luteinizing hormone-releasing hormone LHRH agonists such as leuprolide and goserelin. These agents cause tonic stimulation of the LHRH receptor with the loss of its normal pulsatile activation resulting in decreased output of LH by the anterior pituitary. Therefore as primary hormonal manipulation in prostate cancer one can choose orchiectomy or leuprolide but not both. The addition of androgen receptor blockers including flutamide or bicalutamide is of uncertain additional benefit in extending overall response duration the combined use of orchiectomy or leuprolide plus flutamide is referred to as total androgen blockade. Tumors that respond to a primary hormonal manipulation may frequently respond to second and third hormonal manipulations. Thus breast tumors that had previously responded to tamoxifen have on relapse notable response rates to withdrawal of tamoxifen itself or to subsequent addition of an aromatase inhibitor or progestin. Likewise initial treatment of prostate cancers with leuprolide plus flutamide may be followed after disease progression by response to withdrawal of flutamide. These responses may result from the removal of antagonists from mutant steroid hormone receptors that have come to depend on the presence of the antagonist as a .
