雄激素受体（AR）基因（CAG）n和（GGN）n长度多态性与使用非那雄胺治疗雄激素性脱发后出现长期不良影响的年轻男性的症状
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.
作者信息
Cauci Sabina, Chiriacò Giovanni, Cecchin Erika, Toffoli Giuseppe, Xodo Serena, Stinco Giuseppe, Trombetta Carlo
机构信息
Department of Medical and Biological Sciences, School of Medicine, University of Udine, Udine, Italy.
Urological Hospital Department, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
出版信息
Sex Med. 2017 Mar;5(1):e61-e71. doi: 10.1016/j.esxm.2016.11.001. Epub 2016 Dec 23.
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.
引言
近期有报道称，使用口服非那雄胺治疗雄激素性脱发的男性出现的长期不良症状被称为非那雄胺后综合征（PFS）。
目的
确定雄激素受体（AR）基因中的（CAG）n-rs4045402和（GGN）n-rs3138869多态性是否与PFS有关。
方法
根据PFS症状，对66名白人参与者（31.8%为意大利人，28.8%为美国人，39.4%为其他种族）的AR多态性进行了研究。
主要观察指标
通过一份专门设计的100项问卷、亚利桑那性经验量表和老年男性症状量表（AMS）对症状进行调查。（CAG）n和（GGN）n重复序列被分为短（[CAG]9-19，[GGN]<23）、中（[CAG]20-24，[GGN]23）或长（[CAG]25-37，[GGN]>23）。
结果
中位年龄为32岁，非那雄胺使用时间为360天，停用非那雄胺后的时间为1053天。我们观察到，根据（CAG）n和（GGN）n重复次数，症状出现了几种频率差异。AMS的三个项目在（GGN）23中等重复序列携带者中比在（GGN）>23长重复序列携带者中更严重，一个项目在（GGN）<23短重复序列携带者中更严重。性欲或 libido降低的AMS项目在（CAG）9-19短重复序列携带者中比在（CAG）20-24中等重复序列携带者中更严重。通过专门设计的问卷，在（CAG）n和/或（GGN）n重复序列中，发现阴茎不适、阴囊敏感性丧失、阴囊不适、阴毛减少、会阴部饱满感丧失、精子密度增加、不自主肌肉痉挛、肌肉张力丧失、体重增加（>2kg）、皮肤干燥增加以及非那雄胺使用后症状出现等方面有显著发现。
结论
本研究表明，根据PFS患者报告的症状，短和/或长的（CAG）n和（GGN）n重复序列具有不同的频率，这可能反映了由AR调节的大量基因。本研究显示皮肤干燥症状的（CAG）n重复序列呈U型曲线分布，其中两个极端情况比中等重复序列表现更差。有必要进一步开展研究，采用精准医学方法来探究PFS的病理生理学。
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