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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.

ABSTRACT: INTRODUCTION:Long-term adverse symptoms of men who used oral finasteride against androgenic alopecia have been recently described as post-finasteride syndrome (PFS). AIM:To determine whether (CAG)n-rs4045402 and (GGN)n-rs3138869 polymorphisms in the androgen receptor (AR) gene are implicated in PFS. METHODS:AR polymorphisms were studied according to PFS symptoms in 66 white participants (31.8% Italian, 28.8% American, and 39.4% other). MAIN OUTCOME MEASURES:Symptoms were investigated by an ad hoc 100-item questionnaire and the Arizona Sexual Experience Scale and Aging Male Symptom Scale (AMS). (CAG)n and (GGN)n repeats were categorized as short ([CAG]9-19, [GGN]<23), medium ([CAG]20-24, [GGN]23), or long ([CAG]25-37, [GGN]>23). RESULTS:Median age was 32 years, duration of finasteride use was 360 days, and time from finasteride discontinuation was 1,053 days. We observed several frequency differences in symptoms according to (CAG)n and (GGN)n repeat numbers. Three AMS items were worse for medium (GGN)23 than for long (GGN)>23 carriers and one item was worse for short (GGN)<23 carriers. The AMS item for decrease in sexual desire or libido was worse for short (CAG)9-19 carriers than for medium (CAG)20-24 carriers. 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. CONCLUSION:This study showed that short and/or long (CAG)n and (GGN)n repeats had different frequencies according to symptoms reported by patients with PFS, likely reflecting the vast array of genes modulated by the AR. This study showed a U-curvilinear profile of (CAG)n repeats for skin dryness symptoms, where the two extremes exhibited a worse condition than medium repeats. Further studies are necessary to investigate the PFS pathophysiology using a precision medicine approach.

SUBMITTER: Cauci S

PROVIDER: S-EPMC5302381 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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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 Sabina S Chiriacò Giovanni G Cecchin Erika E Toffoli Giuseppe G Xodo Serena S Stinco Giuseppe G Trombetta Carlo C

Sexual medicine 20161223 1

<h4>Introduction</h4>Long-term adverse symptoms of men who used oral finasteride against androgenic alopecia have been recently described as post-finasteride syndrome (PFS).<h4>Aim</h4>To determine whether (CAG)n-rs4045402 and (GGN)n-rs3138869 polymorphisms in the androgen receptor (AR) gene are implicated in PFS.<h4>Methods</h4>AR polymorphisms were studied according to PFS symptoms in 66 white participants (31.8% Italian, 28.8% American, and 39.4% other).<h4>Main outcome measures</h4>Symptoms ...[more]

PMID: 28024997

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Project description:The use of finasteride for alleviating hair loss has been investigated, and it has been applied as an oral dose medication. However, due to the inconvenience of daily drug administration over long period of time, novel controllable finasteride delivery has been actively investigated. As a novel method of finasteride delivery, the development of finasteride‑loaded microspheres for subcutaneous administration is becoming increasingly pharmaceutically important. Therefore, the present study aimed to use finasteride‑loaded microspheres in a controlled manner in an attempt to overcome the limitations of the oral administration of finasteride and to cause fewer adverse effects. Finasteride‑loaded microspheres containing poly(lactic‑co‑glycolic acid) and finasteride at a ratio of 4:1 were prepared, and a testosterone‑induced androgenic alopecia mouse model was used. Following observation for 10 weeks, the percentage hair growth was 86.7% (total hair growth 60%, partial hair growth 26.7%) in the orally‑applied finasteride‑treated group as a positive control, and 93.3% (total hair growth 60%, partial hair growth 33.3%) in the finasteride‑loaded microspheres‑treated group. Serum dihydrotestosterone levels began to decrease at week 6 in the orally‑applied finasteride‑ and finasteride‑loaded microsphere‑treated groups. In addition, the finasteride‑loaded microspheres‑treated group exhibited similar follicular number, follicular length, anagen/telogen ratio and hair bulb diameter values to those of the orally‑applied finasteride‑treated group. Furthermore, the finasteride‑loaded microspheres increased the activities of phosphoinositide 3‑kinase/protein kinase B and Wnt/β‑catenin in relation to hair follicle cell growth signaling in mouse skin, and suppressed the apoptosis of hair follicle cells by reducing the expression of transforming growth factor‑β2 and caspase‑3, which are indicators of apoptosis. In conclusion, the administration of a single injection of finasteride‑loaded microspheres was effective in treating testosterone‑induced alopecia. Furthermore, it led to equivalent hair growth effects when compared with orally‑applied finasteride, thus revealing the possibility of effective treatment via different routes of administration.

Project description:ObjectivePolycystic ovarian syndrome (PCOS) refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk.MethodsCAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003) inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls.ResultsCAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles) did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles) showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2) = 4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases.ConclusionCAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short/extreme-sized alleles in the cases may be a chance finding without any true association with PCOS risk.

Dataset Information

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.

Publications

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.

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