After suffering from extreme sexual side effects from taking the drug finasteride (propecia) my doctor has theorized that the drug interacts with CAG repeats at the androgen receptor level - causing androgen insensitivity - which is normally a genetic defect from birth - how is it possible that a pharmaceutical with, supposedly, no affinity with for the androgen receptor has the ability to do this?
Here is his post from web MD
http://boards.medscape.com/forums?128@@.29ff6000!comment=1
Several young men seen for hypogonadism (low libido, erectile dysfunction, low energy, etc) after using finasteride have been found to have low-normal levels of bio-available testosterone and LH. This leads to the question of whether partial androgen resistance is at play. It has been shown that androgen insensitivity can occur even without mutations in the genes coding for the androgen receptor1. How then to connect finasteride use to the development of partial androgen resistance, especially outlasting the use of the drug?
In recent years many scientists have looked at the androgen receptor gene with an eye towards a variable length of its structure in one particular region called exon-1. In this region the number of CAG repeats, which code for glutamine (an amino acid-building block for the protein that becomes part of the receptor), vary between approximately 10-25 in different individuals and this variability has been linked to variable effectiveness or potency of androgens (testosterone(T) and dihydrotestosterone (DHT)) in these individuals. In other words, the number of these CAG repeats in the gene for the androgen receptor will effect the functionality of androgens in a man in various tissues in his body and even in his psychological traits2. This variability can cause hypogonadism in men with normal levels of testosterone, which is what androgen resistance is.
Many recent studies have looked at the CAG-repeat length of the androgen receptor in the setting of various clinical settings and found a causal relationship: in mediating the expression of testosterone deficiency on depressive symptoms, on personality traits (neuroticism, extraversion), amygdala reactivity to threat-related facial expression, body composition (muscle and fat) and circulating levels of sex hormones in young and aging men, on memory function in women, and even to solitary sexual desire in male-to-female transexuals. One study in 20053 linked the effectiveness of finasteride on men with baldness with the number of these CAG triplet repeats; the smaller the repeat number, the higher the improvement with finasteride.
I am wondering whether the propensity of finasteride to cause lasting partial androgen resistance in a subset of men relates to the number of CAG repeats in exon 1 of their androgen receptor genes, perhaps those with the greatest number of repeats are at highest risk. I cannot even guess how finasteride would do this after the drug is discontinued, but it is certainly a testable hypothesis. Take 2 groups of men, one group without any post-finasteride hyposexuality and one group with, and measure the androgen receptor gene CAG repeat length in both groups and compare. If it is the case, then men could be assessed, by a blood test prior to using finasteride, as to the risk of developing prolonged hypogonadism from the drug.
1. Clin Endocrinol (Oxf). 1996 Dec;45(6):733-9.
2. Int J Androl. 2003 Apr;26(2):76-83.
3. J Investig Dermatol Symp Proc. 2005 Dec;10(3):293-4.
Looking for any information/opinions any intelligent minds may have.
