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发表于 2015-10-15 10:50:13
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本帖最后由 好头发翻译小组 于 2015-10-15 11:02 编辑
5.Adverse effects
5.副作用
Adverse effects from finasteride are rare.[4] The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA, which could mask the development of prostate cancer.[10][11]
非那雄胺片的副作用并不多。美国食品药品管理局已经发出了一个警告,称5α还原酶抑制剂会增加前列腺癌发病率,因为治疗前列腺会降低前列腺特异性抗原,这恰好掩饰了前列腺癌的发展。
Although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not increased, there are post-marketing reports of breast cancer in association with its use. Available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.[7][12]
尽管临床实验表明服用5mg非那雄胺后男性乳腺癌总体的发病率并没有增加,但是在使用这种药物之后有发生乳腺癌的报道。现在没有很明确的证据证明使用非那雄胺和发生这种癌症之间有联系。
The effect of finasteride on sexual function is controversial. There are case reports of persistent diminished libido or erectile dysfunction after stopping the drug and the FDA has updated the label to inform healthcare professionals of these reports.[8][13] A 2010 review found moderate quality evidence that finasteride increased the risk of sexual dysfunction, but not of discontinuing treatment due to sexual side effects.[14]
非那雄胺片对性功能的影响是有争议的。有病例报告称停止使用菲娜性能之后会发生持续性性欲减弱,以及勃起困难,美国食品药品管理局已经将这些病例通知给了一些专业的保健人员了。在2010年一份调查报告中发现使用非那雄胺会增加性功能障碍的发病率,但是这种情况是因为在使用过程中有副作用的前提下还在坚持服药所导致的。
A 2015 meta analysis found none of the clinical trials had adequate safety reporting and did not provide sufficient information to establish the safety profile for finasteride's treatment of hairloss. The study concluded the existing clinical trials of finasteride for hair loss provide very limited information on toxicity, are of poor quality, and seem to be systematically biased toward under detection of adverse events. Moreover, the trials submitted to the FDA for approval for hair loss excluded most men who would normally be prescribed finasteride for androgenic alopecia.[15][16]
Meta在2015临床试验分析中发现现在既没有足够的安全报告也没有建立有关非那雄胺在治疗脱发在安全性方面足够的信息。研究发现:现在的临床试验基本不能说明非那雄胺在治疗脱发所带来的病毒性,这些临床实验本身也有很多缺陷,并且它似乎是偏向不良事件检测系统下所得出的结果。此外,在向食品药品管理局提交有关允许使用这种药治疗脱发的案例中缺少了很大一部分那些诊断为雄性激素脱发后会自然选择非那雄胺来治疗这样的群体。
When finasteride was originally approved for hair loss in 1997, the FDA approval review reported that it appears well tolerated, with the most common side effects being related to sexual function.[17] In many people these side effects resolve if the medication is stopped and occasionally resolve even if the medication is continued.[17] They additionally state "the sexual functioning questionnaire seems to have given a sensitive reflection of the disturbance on sexual functioning".[17]
当非那雄胺这种药在1997年被批准用来治疗脱发时,食品药品管理局审查报告表示:这种要具有良好的耐受性,有关它最常见的副作用是性功能障碍。如果停止用药或者持续用药一段时间,很多人的这种副作用就会消失。他们还提出,性功能调查问卷似乎对那些性功能障碍的人来说是一个很敏感的话题。
6.Mechanism of action
作用机理
Finasteride is a 5α-reductase inhibitor, specifically the type II and III isoenzymes.[3][18] By inhibiting 5α-reductase, finasteride prevents conversion of testosterone to dihydrotestosterone (DHT) by the type II and III isoenzymes, resulting in a decrease in serum DHT levels by about 65–70% and in prostate DHT levels by up to 85–90%,[3][19] where expression of the type II isoenzyme dominates. Unlike triple inhibitors of all three isoenzymes of 5α-reductase like dutasteride which can reduce DHT levels in the entire body by more than 99%,[3]finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with 100-fold less affinity for I as compared to II.[7] In addition to blocking the type II and III isoenzymes, finasteride competitively inhibits the 5β-reductase type II isoenzyme,[20] though this is not believed to affect androgen metabolism.
非那雄胺是一种5α还原酶抑制剂,特别是针对II型和III型同工酶。通过抑制5α还原酶的产生,非那雄胺抑制了睾酮在II型与III型同工酶作用下向双氢睾酮(DHT)转化的过程,最终使得血液中的双氢睾酮浓度下降65%到70%同时使得前泪腺中的双氢睾酮含量下降多大85%到90%,在这些器官中原本含有大量的II型同工酶。与抑制所有三个同工酶的度他雄胺不同,非那雄胺不能使得体内的DHT含量减少高达99%。主要原因在于非那雄胺缺乏对I型同工5α还原酶抑制剂,因此对于I型同工酶的抑制效应显著若于对II型同工酶的抑制作用,使得其并不能像度他雄胺一样完全抑制DHT的产生。而为了抑制II型和III型同工5α还原酶的产生, 度他雄胺完全阻断了II型同工5α还原酶的产生,尽管这种物质不被认为影响着雄激素的代谢。
By blocking DHT production, finasteride reduces androgen activity in the scalp. In the prostate, inhibition of 5α-reductase reduces prostate volume, which improves BPH and reduces risk of prostate cancer. Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[21]
通过抑制DHT的产生,非那雄胺减少雄激素在头皮上的活性。在前列腺中,5α还原酶减少改善了前列腺增生同时降低了患前列腺癌的风险。同时5α还原酶的减少降低了附睾的重点,减少了附睾中正常形态的精子及其活力。
DHT helps activate the GABAA receptor, which functions to tamp down signaling among neurons; because finasteride prevents the formation of DHT, it may contribute to a reduction of GABAAactivity. Reduced GABAA has been implicated in depression, anxiety, and sexual dysfunction.[22][23][24]
DHT有助于激活GABA受体,这一效应抑制神经元之间的信号传递。由于非那雄胺对于DHT的抑制作用使得GABA活性降低,而GABA的降低对于抑郁、焦虑和性功能障碍产生有着一定的影响。
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