The medication has largely been replaced by newer and improved NSAAs, namely bicalutamide and enzalutamide, due to their better efficacy, tolerability, safety, and dosing frequency (once per day), and is now relatively little-used. It is on the World Health Organizations List of Essential Medicines. Medical uses
Prostate cancer
GnRH is released by the hypothalamus in a pulsatile fashion; this causes the anterior pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates the testes to produce testosterone, which is metabolized to DHT by the enzyme 5α-reductase.DHT, and to a significantly smaller extent, testosterone, stimulate prostate cancer cells to grow. Therefore, blocking these androgens can provide powerful treatment for prostate cancer, especially metastatic disease. Normally administered are GnRH analogues, such as leuprorelin or cetrorelix. Although GnRH agonists stimulate the same receptors that GnRH does, since they are present continuously and not in a pulsatile manner, they serve to inhibit the pituitary gland and therefore block the whole chain. However, they initially cause a surge in activity; this is not solely a theoretical risk but may cause the cancer to flare. Flutamide was initially used at the beginning of GnRH agonist therapy to block this surge, and it and other NSAAs continue in this use. In contrast to GnRH agonists, GnRH antagonists dont cause an initial androgen surge, and are gradually replacing GnRH agonists in clinical use.There have been studies to investigate the benefit of adding an antiandrogen to surgical orchiectomy or its continued use with a GnRH analogue (combined androgen blockade (CAB)).
Medulloblastoma is the second-most frequent brain tumor in children after pilocytic astrocytoma and the most common malignant brain tumor in children, comprising 14.5% of newly diagnosed brain tumors. In adults, medulloblastoma is rare, comprising fewer than 2% of CNS malignancies.The rate of new cases of childhood medulloblastoma is higher in males (62%) than females (38%), a feature that is not seen in adults. Medulloblastoma and other PNET`s are more prevalent in younger children than older children. About 40% of medulloblastoma patients are diagnosed before the age of five, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19. Research models
Using gene transfer of SV40 large T-antigen in neuronal precursor cells of rats, a brain tumor model was established. The PNETs were histologically indistinguishable from the human counterparts and have been used to identify new genes involved in human brain tumor carcinogenesis. The model was used to confirm p53 as one of the genes involved in human medulloblastomas, but since only about 10% of the human tumors showed mutations in that gene, the model can be used to identify the other binding partners of SV40 Large T- antigen, other than p53. Recently a SHH-type mouse model with high incidence of medulloblastoma, a Patched 1 heterozygous mice knockout for the medulloblastoma suppressor Tis21 (Patched1+-/Tis21 KO). The high medulloblastoma frequency appears to be caused by the down regulation of Cxcl3, being Cxcl3 induced by Tis21.