Cyproterone is a steroidal antiandrogen that competitively inhibits the binding of testosterone or DHT to AR. Cyproterone binds to ARs that are expressed by prostate cancer cells as well as to the AR that are expressed in the hypothalamus and pituitary. Therefore, cyproterone blocks the negative feedback of androgens at the hypothalamic-pituitary level leading to increased luteinizing hormone (LH) serum levels. This rise in LH levels causes an increase in serum testosterone levels and ultimately diminishes the ability of cyproterone to compete for AR binding and to block androgenic stimulation.
Cyproterone acetate was developed to overcome this problem. It is formed by adding an acetate group to cyproterone, see figure 3. Cyproterone acetate has a dual mode of action as it competes directly with DHT for binding to AR, but also inhibits gonadotropin secretion. It thereby reduces androgen, estrogen and LH levels. Cyproterone acetate acts both directly as an antiandrogen in prostate cancer cells and also functions to indirectly decrease serum testosterone levels. The latter causes the limitations of cyproterone acetate, which are central effects on androgen secretion, with subsequent loss of libido and sexual potency. Several reports also state that cyproterone acetate causes liver hyperplasia. These side effects gave pharmaceutical companies the incentive to search for alternative, "pure" NSAAs that would not have these side effects.  Pure antiandrogens block the androgen receptor without exerting any agonistic or any other hormonal activity.
Flutamide became the first NSAA to be tested clinically. Later the NSAAs bicalutamide and nilutamide were developed. The alleged advantages of these compounds were that they did not affect libido or potency like the other centrally acting compounds under development, luteinizing-hormone-releasing hormone (LHRH) agonists and cyproterone acetate. But this theory did not prove to be true. These NSAAs eventually crossed the blood–brain barrier, like cyproterone acetate, leading to a subsequent increase in serum testosterone levels.