text: At the beginning of the twentieth century, a relationship between the pituitary, testes and prostate gland had been established. 
  American physician Charles Brenton Huggins found out that castration or estrogen administration led to glandular atrophy in men, which could be reversed by re-administration of androgen. In 1941 Huggins treated prostate cancer patients by androgen ablation with either castration or estrogen therapy; the beneficial effect of androgen ablation on metastatic prostate cancer was realised, for which he was awarded the Nobel Prize in Physiology or Medicine in 1966.
  It became evident that androgen ablation alone was insuffient to cure patients with advanced prostate cancer. In the late 1960s, the androgen receptor (AR) was discovered and characterized. Screening of chemical libraries for AR blockers led to the discovery of the first antiandrogen, cyproterone. An acetate group was then added to cyproterone and created cyproterone acetate. In the 1970s, the antiandrogen flutamide was discovered. 
  In 1989 the United States Food and Drug Administration (FDA) approved it for use the treatment of prostate cancer. 
  In 1995, bicalutamide was approved, and nilutamide followed a year later.