Questioning the Wisdom of Combined Androgen Therapy

One of the questions that often come up is how long a man should use an antiandrogen drug like Casodex along with a GnRH agonist like Lupron or Zoladex?  There is no question that an antiandrogen needs to be used before the first dosage of the agonist (Lupron), but should the antiandrogen be stopped or should it be continued along with the agonist (combining an antiandrogen along with the GnRH agonist is often referred to as a combined androgen blockade)?

The concept of using a combined androgen blockade has been debated since the 1990s. A literature search reveals that there were at least 27 randomized trials evaluating the usage of an antiandrogen in combination with castration. The surprise is that just three of these showed an improvement in survival, leading many doctors to be skeptical of the concept of combining an antiandrogen with a GnRH agonist.

To understand the problem, as with much research, we need to dig behind the studies.  At the time these studies were completed, what was not well appreciated and taken into consideration is the concept of the antiandrogen withdrawal phenomenon.

We now know that men who are on long-term, continuous antiandrogen therapy will stop being positively affected by the drug and will experience prostate cancer disease progression. This leads us to wonder how even three of the studies mentioned above increased survival. 

We are still faced with the question, how long, if at all, should a man continue taking an antiandrogen once they start therapy with drugs like Lupron or Zoladex?