Androgen Receptor (AR) Gene (CAG)n and (GGN)n Length Polymorphisms and Symptoms in Young Males With Long-Lasting Adverse Effects After Finasteride Use Against Androgenic Alopecia
Cauci et al., 2017
“Our investigation using a precision medicine approach suggested genetic implications in symptoms of patients with PFS.”
Cauci et al. explored the relationship of AR polyglutamine stretch-encoding (CAG) and polyglycine stretch-encoding (GGN) polymorphisms with the individual symptoms of Post-Finasteride Syndrome in 66 patients experiencing symptoms for a median of three years after cessation.
Patients were asked to describe their trend of symptoms after discontinuation (improved, unchanged or worsening). 57.6% of PFS patients responded that their trend after was worsening.
Androgen receptor polymorphisms were correlated to the frequency of several PFS symptoms. Patients completed a bespoke symptom questionnaire in addition to the ASEX and the AMS. While total scores of the ASEX and AMS did not differ with length of (CAG)n and (GGN)n repeats, significant differences were found within individual PFS symptoms.
Patients with shorter CAG repeat lengths (9-19) used finasteride for a shorter time than those with medium (20-24) or long (≥25) repeat lengths, and 83.3% of this short CAGn group reported severe libido loss, scoring 5 on item 17 of the AMS. Increased body weight (>2kg) following use of finasteride was most associated with those with long CAG repeats. Interestingly, skin dryness showed a parabolic curvilinear profile, with short and long CAGn groups having higher frequencies (50% and 63.6% respectively) than the medium CAGn group (18.9%). Muscle spasms were found to be more frequent amongst long CAGn carriers (72.7%). Patients with long (>23) GGN repeats did not report experiencing scrotal pain compared with 34.1% of those with medium (23) GGN repeats and 32.7% of those with medium to short length (≤23) repeats. Penile pain was likewise more often seen in those with short or medium rather than long GGN repeats (34.6% vs 7.1%). Long GGN repeats were also associated with a better phenotype regarding fatigue, loss of vitality, depression and the feeling of passing one’s peak than those with medium repeats. Loss of perineal fullness was reported by 100% of men with short GGNn repeat lengths, 70.5% of men with medium GGN repeats and 57.1% of those with long repeats.
The authors note that tissue-specific effects and epigenetic changes occurring in a single individual can modulate the action of receptors. They conclude there is a need for much more research into the pathophysiology of PFS.
