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

Introduction: Long-term adverse symptoms of men who used finasteride as oral drug against androgenic alopecia (AGA) have been recently described as Post-Finasteride Syndrome (PFS). Aim: We explored whether (CAG)n-rs4045402 and (GGN)n-rs3138869 polymorphisms in the androgen receptor (AR) gene are implied in PFS. Methods: AR polymorphisms were studied according to PFS symptoms in 66 White participants, of whom 31.8% were Italians, 28.8% US-Americans, followed by other Countries. Main Outcome Measures: Symptoms were investigated by an ad-hoc 100-questions’, Arizona Sexual Experience Scale (ASEX), and Aging Male Symptom Scale (AMS) questionnaires. (CAG)n and (GGN)n repeats were categorized as short (CAG)9-19, (GGN)<23; medium (CAG)20-24, (GGN)23; and long (CAG)25-37, (GGN)>23 repeats, respectively. Results: Median age was 32 years, duration of finasteride use 360 days, and time from finasteride discontinuation 1053 days. We observed several frequency differences in symptoms according to (CAG)n and (GGN)n repeats’ number. Three AMS items were worse in medium (GGN)23 than in long (GGN)>23, and 1 item than in short (GGN)<23. AMS item decrease in sexual desire/libido was worse in short (CAG)9-19 than in medium (CAG)20-24 repeats. Through the ad-hoc questionnaire significant findings in (CAG)n and/or (GGN)n repeats were obtained for: penile discomfort, loss of scrotal sensitivity, scrotal discomfort, less pubic hair, loss of perceived perineal fullness, increased sperm density, involuntary muscle spasms, loss of muscle tone, increased weight (>2 kg), increased skin dryness, and onset of symptoms after finasteride use. Conclusions: We first observed that the short and/or long (CAG)n and (GGN)n repeats had different frequencies according to symptoms experienced by PFS patients, likely reflecting the vast array of genes modulated by the AR. Our study evidenced an U-curvilinear profile of (CAG)n repeats for skin dryness symptoms, where both extremes had a worse condition than medium repeats. Further studies are necessary to investigate the PFS pathophysiology using a precision medicine approach.