AntiAndrogen Withdrawal Syndrome
The antiandrogen withdrawal syndrome or antiandrogen withdrawal response (AAWR) is a phenomena that can occur in men with progressing prostate cancer after they stop using antiandrogens. It leads to a symptomatic improvement and reduced PSA levels. This is of course the opposite what you might expect considering prostate cancer is fuelled by T/DHT.
There are 2 large differences between AAWR and PFS.
- It only occurs in cancer cells.
- Not permanent, lasts an average of 5 months.
If you crashed after stopping Finasteride you are suffering from a kind of antiandrogen withdrawal syndrome. So its useful to look at what causes AAWR.
Theories
The molecular mechanism behind AAWR is unknown. There are some published theories I have listed them below. (Sources here [1] and [2] .)
• Androgen receptor mutation. Binding specifity altered to allow other hormones or antiandrogens to effect the AR. (antagonist becomes agonist etc.)
• Non-androgen receptor pathway is activated by the antiandrogen causing ligand-independent cancer growth which stops after use.
• Androgen receptor over-expression. Amplifying the effect of low levels of androgens and the weak agonist effects of antiandrogens. Associated with alterations in the recruitment of coactivators and corepressors to the promoters of the androgen receptor.
• Macrophages/Cytokines. IL-1 can convert androgen antagonists into agonists in cancer cells.
The focus of AAWR theories are on what is present during antiandrogen treatment that could of caused the cancer to grow, NOT on a ‘downregulated’ response to androgens occuring after antiandrogen treatment ends.