Key result
Long-term use of finasteride and dutasteride induces a novel state of androgen deficiency that may be associated with health risks including non-alcoholic fatty liver disease, insulin resistance, type 2 diabetes, dry eye disease, and kidney dysfunction.
Why the study?
The physiological roles of 5a-DHT remain poorly appreciated, raising concerns that 5a-reductase inhibition by finasteride or dutasteride induces tissue-specific androgen deficiency contributing to unrecognized pathophysiological conditions.
Does long-term use of finasteride or dutasteride increase the risk of metabolic dysfunctions such as NAFLD, insulin resistance, type 2 diabetes, dry eye disease, and kidney disease in men with BPH or AGA?
Does long-term use of finasteride or dutasteride increase the risk of metabolic dysfunctions such as NAFLD, insulin resistance, type 2 diabetes, dry eye disease, and kidney disease in men with BPH or AGA?
Long-term inhibition of 5α-reductase by finasteride and dutasteride may induce a novel state of tissue-specific androgen deficiency, leading to significant metabolic and physiological adverse effects.
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.
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Abdulmaged M. Traish (2020) conducted a review in Benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). Finasteride and Dutasteride was evaluated. Long-term use of finasteride and dutasteride induces a novel state of androgen deficiency that may be associated with health risks including non-alcoholic fatty liver disease, insulin resistance, type 2 diabetes, dry eye disease, and kidney dysfunction.
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