Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm

Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm
Abdulmaged M Traish 1

World J Mens Health. 2020 Jul; 38(3): 323–337.
Published online 2020 Mar 20. doi: 10.5534/wjmh.200012
PMCID: PMC7308241

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.

Keywords: 5-alpha reductase inhibitors; Diabetes mellitus; Dry eye syndromes; Hypogonadism; Kidney diseases; Non-alcoholic fatty liver disease.

Full Study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308241/

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In the 1990s, the medical cartel proposed that 5-alpha reductase enzymes were relatively "unimportant" and that inhibiting their expression was completely safe and effective in lowering the “nefarious” DHT.

Quoted from above paper:

“5α-reductases (5α-Rs), a family of several isozymes, play an important role in human physiology by regulating cellular metabolism of androgens, glucocorticoids and other steroids. 5α-Rs are the rate limiting step in the biosynthesis of neuroactive steroids which are critical for central nervous system function.” 

Beyond DHT, which we now understand plays a crucial role in physiology, inhibiting the 5α-Rs is clearly dangerous and foolhardy. 

The above paper (above) highlights the various roles of these enzymes in the regulation of countless hormones and cellular processes. 

The treatments finasteride and dutasteride are now implicated in such various problems as insulin sensitivity, dry eye disease, type 2 diabetes, fatty liver diseases, and kidney function.

Here are a few quotes from the article illustrating the extent of the importance of 5αlpha Reductas(s):

“In men, inhibition of 5α-R types 1 and 2 with dutasteride resulted in hepatic IR, hepatic lipid accumulation, and decreased adipose lipid mobilization, without impacting peripheral insulin sensitivity. Insulin-regulated metabolites levels changed significantly in response to finasteride or dutasteride treatments.”

“Zhang et al. and Li et al. described the effects of 5α-DHT inhibition by finasteride on ‘lacrimal gland histopathology’ and ‘ocular function’. Finasteride administration effectively induced dry eye in rats by 14 days after administration.”
“Finasteride also altered the apoptotic/proliferating ratio of nephron cells and the increased lymphocytes infiltrations into the area of pathologically altered convoluted tubules were accompanied by impaired androgen/estrogen homeostasis.”

Far from being harmless, 5-αlpha Reductas(s) profoundly affect virtually every system in the human body. 

Of course, they are intimately linked to DHT. 

While testosterone is crucial steroid, it is DHT which seemingly acts directly on many tissues:

“The wide expression and distribution of 5α-Rs in many tissues and organs suggests that although Testosterone 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.”

Hence, if we inhibit the conversion of testosterone into DHT via the 5α-reductase enzymes, far from curing male pattern baldness, we probably wreck havoc on fundamental processes which depend upon the expression of these enzymes and the direct action of DHT. 

The article goes into greater detail and presents a very large body of evidence showing how dangerous the 5α-reductase inhibiting treatments really are.

Basic synopsis of the paper:
 
“Because finasteride and dutasteride are often ‘given’ to treat LUTS in men with BPH and male pattern hair loss in men with AGA for prolonged periods of time, it is postulated that men treated with these ‘treatments’ are in a state of androgen deficiency and are at high risk of developing NAFLD IR, T2DM, dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. For these reasons, we believe that the clinical community should recognize these new potential health risks associated with these ‘treatments’ and we believe ‘it's time to sound the alarm’ on these ‘treatments.’”

Maybe it would be safer and not so systemic if those drugs were crushed and dissolved in a topical solution of minoxidil.

shaftless wrote:Maybe it would be safer and not so systemic if those drugs were crushed and dissolved in a topical solution of minoxidil.

"Minox-a-Kill" will systemically absorb and it will derange collagen synthesis.

Rats! Maybe a somewhat absorbing emu oil based cream instead?

Would taking Dutasteride topically affect the body the same as doing it internally?

moj wrote:Would taking Dutasteride topically affect the body the same as  doing it internally?

Definitely less detrimental.

Sometime ago I posted a study on a natural topical. that at least bests finasteride.

https://www.sciencedirect.com/science/article/pii/S0753332221000263

CS and at this point you still recommend using Retinol A cream to help it absorb or is there a better option available?

moj wrote:CS and at this point you still recommend using Retinol A cream to help it absorb or is there a better option available?

I don't recall mentioning Retinol A cream, might have been someone else.

CausticSymmetry wrote:

moj wrote:Would taking Dutasteride topically affect the body the same as  doing it internally?

Definitely less detrimental.

Sometime ago I posted a study on a natural topical. that at least bests finasteride.

https://www.sciencedirect.com/science/article/pii/S0753332221000263

Glad to know that you look upon the FIN/DUT as much less risky when used topically. I would absolutely never touch these compounds orally, but I admit that recently I have been weighing up the pros and cons of topical use. Do you think there is any credibility to the molecular dalton size of the Dutasteride molecule being so large that it can’t pass through the scalp into systemic circulation? If so, that would be genuinely interesting. The long half life still really scares me, so even if a very small percentage passes through, it could become an issue over time if used more than a few times per week? Rob from ‘perfect hair health’ on YouTube looks at hairloss from a similar naturalistic and analytical lens as you CS, and even one of his posts recently had him saying he was considering topical/mesotherapy dutasteride for his crown. Would love to know your current thoughts on this!

There's been on going work on dutasteride, because as a pure version, it has too much irritation, cytotoxicity.

So researchers explored the potential for dutasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity. They used a combination of melt-dispersion and ultrasonication to prepare DST-NLCs which are negatively charged NLCs with a mean particle size of ~184 nm. These NLCs were coated with lauric acid-chitosan oligomer (CSO-LA) which made their surface charge positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4-8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs.

There was no detectable drug permeation through full-thickness pig ear skin from either preparation.

Anyway that said, there is a clinical trial ongoing that will answer the all important questions:

https://clinicaltrials.gov/ct2/show/NCT05599243

Thanks man, sounds super technical but I’ll try my best to wade through it. Would also be great to hear your expertise on some of the findings when the clinical trial comes to fruition.
Out of curiosity, do you currently use anything topically?

What would be a good home made carrier for dut?

bevnae wrote:Thanks man, sounds super technical but I’ll try my best to wade through it. Would also be great to hear your expertise on some of the findings when the clinical trial comes to fruition.
Out of curiosity, do you currently  use anything topically?

No, never been too focused on topicals. It's always been the inside out approach for me.

Likewise really. Overall health, high metabolism and optimal hormones is my priority and hair health is a lovely byproduct. But if there’s something that’s going to move the needle for hairloss topically, my interest is well and truly piqued. I’m very surprised the 1-2% topical policosanol hasn’t tempted you in any way?