Could provide clues/insight into why certain men like us reacted poorly to the drug at the genetic (androgen receptor) level.
Effectiveness of Finasteride on Patients With Male Pattern Baldness Who Have Different Androgen Receptor Gene Polymorphism
nature.com/jidsp/journal/v10/n3/full/5640229a.html
"Most male pattern baldness (MPB) patients have an androgen-dependent trait, although it is thought to be under the control of multiple genes, such as [u]genes for androgen receptor (AR), insulin-like growth factor-1 (IGF-1), and dihydrotestosterone regulations [/u](Nyholt et al, 2003;Tang et al, 2003).
One of the 5 -reductase inhibitors, finasteride, is effective on MPB, although there is a variation in the efficacy of this drug among the MPB patients. From the functional mechanism of this drug, it is thought to be effective on the MPB caused by hyperfunction of AR.
Association of higher incidence rate of MPB with lower triplet repeat number in the first exon of AR gene has been demonstrated by some authors (Sawaya and Shalita, 1998;Ellis et al, 2001). Tracing their study, we have found that there is a correlation between the symptom levels of MPB and the CAG and GGC repeat numbers in AR gene.1 To investigate the relationship between the effectiveness of finasteride and the AR gene polymorphism, we determined the number of triplet repeats in AR gene of patients.
Effectiveness of finasteride on each patient was expressed as the improvement point of symptom derived from the modified Hamilton–Norwood typing. The number of the triplet repeats (CAG+GGC) was plotted against the symptom points.
There was a broad correlation between these variables Figure 1. The smaller the repeat number, the higher the improvement with finasteride. Patients were divided into two groups: the group comprised of patients whose number of repeats was 40 or less, and the group of more than 40. Larger number of patients in the former group (40) obtained higher improvement points, compared with that in the latter (>40) (data not shown). [
[u]Finasteride was more effective on patients in the short repeat group /u; even they had severe initial symptoms (V–VII). The relation between the improvement points and total dose of fnasteride was analyzed.
In the shorter repeat group (40), their mean improvement point was 0.96 to 1.1 even by a smaller total dose, 30–100 mg, while 200 mg or more was necessary to achieve the same improvement in the long repeat group (>40). Finasteride was less effective on patients in the long repeat group (>40) especially on patients younger than 30 y.
As mentioned above, we have found that the shorter the CAG and GGC repeat numbers, the higher the symptom level before treatment with finasteride. Although, the mean initial symptom of patients in the short repeat group was worse, finasteride was more effective in the improvement of MPB in most patients with shorter triplet regions of AR gene. These cases may be caused by hyperfunction of AR. On the other hand, this drug was less effective in certain cases with longer triplet repeats. They are thought to result from a non-androgenic mechanism. This kind of analysis may aid in the choice of drug for MPB patients.
Graph showing effect of finasteride on patients with different triplet repeat numbers in androgen receptor (AR) gene:
nature.com/jidsp/journal/v10/n3/fig_tab/5640229f1.html#figure-title
