New Study: Long Term Dutasteride Is Associated With Metabolic Alterations

[dr75]

https://www.degruyter.com/view/j/hmbci.2017.30.issue-3/hmbci-2017-0015/hmbci-2017-0015.xml

Summary

This study suggests that long-term dutasteride therapy is associated with increased blood glucose, HbA1c, LDL-cholesterole and TC, potentially leading to increased onset of IR and NAFLD. In addition, dutasteride increased liver transaminase activity and AMS score suggesting increased inflammation and reduced quality of life. Dutasteride therapy also worsened ED and resulted in reduction in T levels. These findings raise serious safety concerns regarding metabolic dysfunction and adverse sexual side effects of long-term dutasteride therapy. Clinicians are strongly urged to discuss these potential health adverse effects of dutasteride treatment with their patients prior to instituting this form of therapy.

Prior to this, there were concerns regarding hepatic inhibition of 5AR1 leading to hepatic lipid accumulation. This new study justified my concerns about dutasteride and made me realize that it is not a safe medication. What do dutasteride users think about this?

Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701851/

 

[g.i joey]

More closure on me never taking dutasteride, finasteride is where I draw the line.

 

[michel sapin]

damn! just when i was about to start duta

i think that 5 mg fina might be safer .

 

[arnoldd]

internet studys sometimes are contraditory. in the glaxo's leaflet there arent any mentions to possible hepatic danger, yes for sexual disfuction ( 7%). there are long term dutas users that take it since 8 or 10 years and i never read anyone claiming having hepatic problems..

 

[nicksparrow]

Eat healthy & exercise ya skanks. PUT THAT STUDY TO SHAME!

.5mg Dutas vs 5mg Finas
"Serum DHT decreased with both treatments as anticipated, although this decrease was statistically significant only with finasteride."
^^^I guess dutas takes longer than 3 weeks to work eh? Or have I been FOOLED?


wait which is it? :O
In a test area at 24 weeks, results showed:

Placebo -32.3 hairs
Finasteride 5mg 75.6 hairs
Dutasteride 0.1 mg 78.5 hairs
Dutasteride 0.5 mg 94.6 hairs
Dutasteride 2.5 mg 109.6 hairs

 

[davesmith420]

Hair > General Health

 

[longtimelurker]

For nine months I've suffered through the sides (my enlarged lower pecs, sudden weight gain, general malaise, and constant mass sheds) for results that from what I've observed so far are equal to Finas. The long-term issues pointed out in this study are enough to finally motivate me to cancel the nuclear option and go back to Finasteride. I can only hope the gyno subsides and my hair count remains stable post-dutasteride.

 

[dr75]

Eat healthy & exercise ya skanks. PUT THAT STUDY TO SHAME!

.5mg Dutas vs 5mg Finas
"Serum DHT decreased with both treatments as anticipated, although this decrease was statistically significant only with finasteride."
^^^I guess dutas takes longer than 3 weeks to work eh? Or have I been FOOLED?


wait which is it? :O
In a test area at 24 weeks, results showed:

Placebo -32.3 hairs
Finasteride 5mg 75.6 hairs
Dutasteride 0.1 mg 78.5 hairs
Dutasteride 0.5 mg 94.6 hairs
Dutasteride 2.5 mg 109.6 hairs

I don't see how exercising will ameliorate impaired gluccocorticoid clearance induced by 5ar1 inhibition.

 

[arnoldd]

You gotta be f*****g kidding me.
Just when i jumped on duta hype train 2 months ago and began to notice thickening, you bring this sh*t now.

Well f*** it. I'll still swallow the pill, better be dead than living the bald dream.

Hahahaha

 

[dralex]

I don't understand the terminology. What is intrahepatic lipid accumulation?

 

[kj6723]

Dutasteride might be dangerous, but going bald is also dangerous, for mental and emotional health

 

[Tisumi2333]

You gotta be f*****g kidding me.
Just when i jumped on duta hype train 2 months ago and began to notice thickening, you bring this sh*t now.

Well f*** it. I'll still swallow the pill, better be dead than living the bald dream.

hahaha.goodluck .hope u have nice hair and good health

 

[michel sapin]

so this is sure that duta ipact the liver ? or just mildy elevate the bad enzyme ?

 

[abcdefg]

You cant use the 2 far and away most effective treatments without health risks, and if you dont then you bald. Its a lose-lose situation.
Where oh where are all the topicals that inhibit androgens LOCALLY? we dont need to inhibit DHT systemically. Look at how hard its proven to be to stop just DHT locally in the last 30 years, and tell me hair multiplication is going to be here anytime soon.

 

[Feelsbadman.jpg]

These studies are what put me off from dutasteride. Any long term dutasteride user that have anything to refute this? Any lab panels with liver results? One of the studies was only 12 people.

 

[Alex Contee]

These studies are what put me off from dutasteride. Any long term dutasteride user that have anything to refute this? Any lab panels with liver results? One of the studies was only 12 people.

I was on dutasteride everyday for 2 years after years on finasteride. Everything that happen to the group happened to me. At one point a dr said I all of the sudden had pre diabetes.

There is one thing even worse than the stuff mentioned in the study and that’s what 50% 5ar1 inhibition does to your brain over time. You will decline cognitively. No amount of exercise or diet will help that. I can only imagine what a life time of taking it ED will do to your brain by the time you are over 65.

If I ever returned to dutasteride, I would take it MWF. If you look up the graphs, it’s still beats finasteride 5ar2 inhibition EOD or even MWF.

0.5mg/day inhibits 50% of 5ar1. So there is a reasonable chance 0.5 mg/day could affect the brain. It inhibits 99% of type 2, from the graph.

0.5mg EOD inhibits 18% of type 1, and 95% of type 2, from reading the graph.

 

[g.i joey]

I was on dutasteride everyday for 2 years after years on finasteride. Everything that happen to the group happened to me. At one point a dr said I all of the sudden had pre diabetes.

There is one thing even worse than the stuff mentioned in the study and that’s what 50% 5ar1 inhibition does to your brain over time. You will decline cognitively. No amount of exercise or diet will help that. I can only imagine what a life time of taking it ED will do to your brain by the time you are over 65.

If I ever returned to dutasteride, I would take it MWF. If you look up the graphs, it’s still beats finasteride 5ar2 inhibition EOD or even MWF.

0.5mg/day inhibits 50% of 5ar1. So there is a reasonable chance 0.5 mg/day could affect the brain. It inhibits 99% of type 2, from the graph.

0.5mg EOD inhibits 18% of type 1, and 95% of type 2, from reading the graph.

Are you back on finasteride?

 

[Feelsbadman.jpg]

I was on dutasteride everyday for 2 years after years on finasteride. Everything that happen to the group happened to me. At one point a dr said I all of the sudden had pre diabetes.

There is one thing even worse than the stuff mentioned in the study and that’s what 50% 5ar1 inhibition does to your brain over time. You will decline cognitively. No amount of exercise or diet will help that. I can only imagine what a life time of taking it ED will do to your brain by the time you are over 65.

If I ever returned to dutasteride, I would take it MWF. If you look up the graphs, it’s still beats finasteride 5ar2 inhibition EOD or even MWF.

0.5mg/day inhibits 50% of 5ar1. So there is a reasonable chance 0.5 mg/day could affect the brain. It inhibits 99% of type 2, from the graph.

0.5mg EOD inhibits 18% of type 1, and 95% of type 2, from reading the graph.

Check out this study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748434/

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.

After two months of .5 mg of dutasteride a day, allopregnanolone leves were still inreasing which means 5AR1 was not being inhibited in brain to any significant extent. I believe dutasteride at .5 mg ED reaches 60% of steady state levels after 1 month and 90% of steady state after 3 months. It seems unlikely that 5AR1 levels in the brain are impacted that much by the standard dose of .5 mg. Now at 2.5mg, it clearly does.

Also, Rick Rosner, the man with the highest or second highest IQ (192 I believe) in the world has been on Avodart since 2005 apparently. I doubt some one that clearly values their intelligence to the extent that he does would continue to take a drug for a decade plus if it caused him to decline cognitively.

This study shows dutasteride offers neuroprotection agaisnt parkinson's disease. https://www.ncbi.nlm.nih.gov/pubmed/28982631

 

[Feelsbadman.jpg]

Been doing some more research about the consequences of long term dutasteride and it seems that they are comparable to finasteride, this means that both finasteride and dutasteride can potentially increase risk of type 2 diabetes.

https://diabetes.medicinematters.co...5-alpha-reductase-inhibitor-link-to-/16664656

Propensity score matching slightly attenuated the risk associated with dutasteride (aHR=1.18) but increased that associated with finasteride (aHR=1.61).

Depending on how the statistics are played with, finasteride can have a higher risk.

Strangely though, there are other studies that show finasteride/dutasteride increases insulin sensitivity which should reduce type 2 diabetes risk. This study states that T+ dutasteride increases insulin sensitivity but T alone does not. https://www.sciencedirect.com/science/article/pii/S1743609515306536

This study on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT01923090) that apparently never completed had the complete opposite hypothesis from the two studies from the OP. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701851/, https://www.degruyter.com/view/j/hmbci.2017.30.issue-3/hmbci-2017-0015/hmbci-2017-0015.xml.

The purpose of this study is to see if an enzyme in the body (5-alpha reductase, 5αR) is important in controlling how the body handles sugar and fat. The investigators believe that 5αR is a crucial step in regulating these actions as well as controlling how insulin works in the body but regulating the amount of steroid hormones including cortisol and testosterone in the body. In previous clinical studies, the investigators have shown that the activity of 5αR increases as you gain weight and decreases with weight loss. In addition, work that the investigators have performed in the laboratory has shown that if you increase 5αR levels in liver cell grown in the laboratory, the amount of fat that they contain increases. The investigators would therefore like to demonstrate the effect of inhibition 5αR on the regulation of insulin, glucose and fat in the body.

This is completely contradictory to some of these other studies. It looks like they are proposing that finasteride and dutasteride would help reduce NAFLD.


I am thinking there is a lot of biases being pushed with some of these studies due to all the contradictions. It seems like some of these studies are based around a pre-concluded result. Then again, this could be my own bias showing through because obviously I want finasteride/dutasteride to be safe and beneficial.

Update:

The head of the proposed study from https://clinicaltrials.gov/ct2/show/NCT01923090 is actually one of the primary authors in the study from the OP. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701851/. I actually emailed him to get some clarification. I will post his reply if he responds and gives permission.

 

[Feelsbadman.jpg]

This is important. https://www.ncbi.nlm.nih.gov/pubmed/24080367

Nonalcoholic fatty liver disease (NAFLD) has been associated with glucocorticoid excess and androgen deficiency, yet in the majority of patients with steatohepatitis, circulating cortisol and androgen levels are normal. The enzyme 5α-reductase (5αR) has a critical role in androgen and glucocorticoid action. We hypothesize that 5αR has an important role in the pathogenesis of steatohepatitis through regulation of intracrine/paracrine hormone availability. Human liver samples from patients with NAFLD and normal donor tissue were used for gene expression and immunohistochemical analysis. NAFLD samples were scored using the Kleiner classification. In addition, 5αR1(-/-), 5αR2(-/-), and wild-type (WT) mice were fed normal chow or American lifestyle-induced obesity syndrome (ALIOS) diet for 6 or 12 months. Liver histology was graded and staged. Hepatic and circulating free fatty acid and triglyceride levels were quantified, and gene and protein expression was measured by real-time PCR and immunohistochemistry. 5αR1 and -2 were highly expressed in human liver, and 5αR1 protein expression increased with severity of NAFLD. 5αR1(-/-) (but not 5αR2(-/-)) mice fed an ALIOS diet developed greater hepatic steatosis than WT mice, and hepatic mRNA expression of genes involved in insulin signaling was decreased. Furthermore, 60% of WT mice developed focal hepatocellular lesions consistent with hepatocellular carcinoma after 12 months of the ALIOS diet, compared with 20% of 5αR2(-/-) and 0% of 5αR1(-/-) mice (P < .05). 5αR1 deletion accelerates the development of hepatic steatosis but may protect against the development of NAFLD-related hepatocellular neoplasia and therefore has potential as a therapeutic target.

It states that deleting 5AR1 in mice and feeding them what they call an "American lifestyle-induced obesity syndrome (ALIOS) diet" led to greater fat accumulation in the liver compared to normal mice and that 5AR1 expression increased in the liver relative to the severity and progression of NAFLD. HOWEVER, normal mice fed the ALIOS diet got what appears to be liver cancer after 12 months (60%) on ALIOS where as 0% of the 5AR1 inhibited mice got these lesions. So while 5AR1 inhibition leads to greater fat accumulation on a western style diet, it prevents liver cancer, so much so that the authors see it as method of treatment.

My own speculation.

DHT is a carcinogenic hormone. So if increased 5AR expression is a coping mechanism to clear out excessive glucocorticoids to minimize their interaction with insulin (this seems to be the prevailing theory based off of"Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man" by Tomlinson et al.) increased DHT could be an unintended consequence. Excessive and prolonged DHT exposure in the liver could lead to cancer. However, it seems odd that such a mechanism would prioritize limiting hepatic steatosis at the expense of possible (actually probable in this study) cancer tumors. Perhaps the modern diet has simply not been around enough for natural selection to sort this out?

Anyway, based off this study, if you are going to eat a western diet, it seems you are still better off on dutasteride and finasteride. The WT mice in the study still developed NAFLD, just at a slower rate than the 5AR 1 and 2 inhibited groups while the WT mice ended up with much higher rates of cancer like tumors on their liver after 1 year. It's not the lack of 5AR that is causing the the fatty liver so much as it's the diet and high insulin. Glucocorticoids in the absence of insulin actually inhibit fat gain, more on that below.

Update:

The head of the proposed study from https://clinicaltrials.gov/ct2/show/NCT01923090 is actually one of the primary authors in the study from the OP. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701851/. I actually emailed him to get some clarification. I will post his reply if he responds and gives permission.

I got a response from one of the authors of https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701851/ (2nd study in OP) and the reason for the conflicting results in vitro with liver cells having 5AR added causing lipid accumulation is due to the nature of glucocorticoids behaving differently depending on what hormones they are interacting with. Glucocorticoids alone inhibit fat gain, but in the presence of insulin (like what happens in vivo), they enhance it. With the liver cells in the lab, they only used cortisol and over-expressed 5AR. In the absence of insulin, Cortisol burns fat and by increasing 5AR you increase Cortisol clearance thereby allowing fat to increase (my understanding).