Traish (2020): Health Risks Associated With Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm

This is the second of Traish’s finasteride-related papers in 2020.

PubMed record
Full text at journal site

This one focuses on metabolic adverse effects. From the full text (emphasis added):

In this review we summarize the reported findings related to finasteride and dutasteride on metabolic adverse effects in liver, muscle, kidney and ocular system [references in full text]. Adverse effects pertaining to sexual dysfunction, depression and suicidal ideation are discussed in previous reviews [2, 7]. Here we will focus on the finding form pre-clinical and clinical studies on the metabolic adverse effects of finasteride and dutasteride and highlight the potential health related risks of these drugs.


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 b-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.


Kinda like closing the barn door after the horses already ran out…


Inhibition of 5α-dihydrotestosterone biosynthesis induces a novel form of androgen deficiency independent of testosterone levels

T is synthesized and secreted by the testis and circulates in plasma as free (unbound) T or bound to sex hormone binding globulin and serum albumin. The unbound fraction of T, known as biologically available free T, enters target and nontarget cells by passive diffusion through the phospholipid plasma membrane (Fig. 6). In androgen target cells, T is further metabolized to 5α-DHT via 5α-Rs. In target cells, both T and 5α-DHT interact with the AR; however, 5α-DHT binds to the AR with approximately 10-fold higher affinity compared with T [35]. This large difference in the affinity of T and 5α-DHT for AR make 5α-DHT the critical physiological androgen modulator in many tissues, and therefore, inhibition of its biosynthesis may result in a novel state of androgen deficiency. The wide expression and distribution of 5α-Rs in many tissues and organs [2] suggests that although T is the main circulating androgen, its conversion to the high affinity 5α-DHT in many of these tissues is responsible for regulating tissue and cellular metabolism and function. Binding of 5α-DHT to AR results in activation and transformation of the AR into a higher affinity complex for DNA and induces its translocation from the cytoplasm to the nucleus where it interacts with the androgen response elements. This high affinity binding to a specific DNA sequences, result in recruitments of AR co-activators or co-repressors, resulting in regulating specific gene expression. This results in changes in cellular metabolism and function.

I think this is what has happened to a lot of people with physical symptoms such as myself with the tissue changes…

Damn it. I’m so scared of the contents of this.
And very sad…