Traish Abdulmaged M
Department of Urology, Boston University School of Medicine, Boston, MA, USA.
World J Mens Health. 2020 Jul;38(3):323-337. doi: 10.5534/wjmh.200012. Epub 2020 Mar 20.
5α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, the physiological role of 5α-DHT in human physiology, remains questionable and, at best, poorly appreciated. Recent emerging literature supports a role for 5α-DHT in the physiological function of liver, pancreatic β-cell function and survival, ocular function and prevention of dry eye disease and kidney physiological function. Thus, inhibition of 5α-reductases with finasteride or dutasteride to reduce 5α-DHT biosynthesis in the course of treatment of benign prostatic hyperplasia (BPH) or male pattern hair loss, known as androgenetic alopecia (AGA) my induces a novel form of tissue specific androgen deficiency and contributes to a host of pathophysiological conditions, that are yet to be fully recognized. Here, we advance the concept that blockade of 5α-reductases by finasteride or dutasteride in a mechanism-based, irreversible, inhabitation of 5α-DHT biosynthesis results in a novel state of androgen deficiency, independent of circulating testosterone levels. Finasteride and dutasteride are frequently prescribed for long-term treatment of lower urinary tract symptoms in men with BPH and in men with AGA. This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. We suggest that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease.
5α-双氢睾酮（5α-DHT）是效力最强的天然雄激素。5α-DHT在许多组织中引发多种生理作用，包括前列腺、精囊、毛囊、皮肤、肾脏以及泪腺和睑板腺。然而，5α-DHT在人体生理学中的生理作用仍然存疑，而且充其量也未得到充分认识。最近出现的文献支持5α-DHT在肝脏生理功能、胰腺β细胞功能与存活、眼部功能以及预防干眼症和肾脏生理功能方面发挥作用。因此，在治疗良性前列腺增生（BPH）或男性型脱发（即雄激素性脱发，AGA）过程中，用非那雄胺或度他雄胺抑制5α-还原酶以减少5α-DHT生物合成，可能会引发一种新的组织特异性雄激素缺乏形式，并导致许多尚未被充分认识的病理生理状况。在此，我们提出这样一个概念，即非那雄胺或度他雄胺以基于机制的、不可逆的方式抑制5α-DHT生物合成，从而阻断5α-还原酶，会导致一种独立于循环睾酮水平的新的雄激素缺乏状态。非那雄胺和度他雄胺经常被用于长期治疗患有BPH的男性和患有AGA的男性的下尿路症状。这种治疗可能会导致非酒精性脂肪性肝病（NAFLD）、胰岛素抵抗（IR）、2型糖尿病（T2DM）、干眼症、潜在的肾功能障碍以及其他代谢功能障碍。我们认为，长期使用非那雄胺和度他雄胺可能与包括NAFLD、IR、T2DM、干眼症和潜在肾病在内的健康风险相关。
