New Study: Long Term Dutasteride Is Associated With Metabolic Alterations

[Kaus Klinski]

worried about the metabolic effects of dutasteride to the point you won't take it, you probably shouldn't take finasteride either

Seems reasonable. However, I take all those upcoming newer studies with a grain of salt anyway. I mean, Finasteride in it's approved bph dosage is on the market for how long now, 30 years? Dutasteride is approved within the U.S. since 2002 AFAIK. So isn't the recent discovery of 5-ari drugs causing/elevating the risk for developing diabetes and NAFLD coming a bit late? At least in clinical practice, no connection between the drugs and the mentioned diseases have ever been observed AFAIK.

Regards
Kaus Klinski

 

[Feelsbadman.jpg]

Seems reasonable. However, I take all those upcoming newer studies with a grain of salt anyway. I mean, Finasteride in it's approved bph dosage is on the market for how long now, 30 years? Dutasteride is approved within the U.S. since 2002 AFAIK. So isn't the recent discovery of 5-ari drugs causing/elevating the risk for developing diabetes and NAFLD coming a bit late? At least in clinical practice, no connection between the drugs and the mentioned diseases have ever been observed AFAIK.

Regards
Kaus Klinski

Yes, my thoughts as well which is why I have decided to take dutasteride .5mg ED. These studies can be misleading. If your risk for type 2 diabetes is already very low, even a 30% increase is not particularly alarming.

 

[Kaus Klinski]

It is a bit of a moot point however when comparing the safety of finasteride vs dutasteride since they both inhibit 5AR type 3.

Yep, definitely.

One could argue that finasteride is a much weaker inhibitor of 5-ar3 compared to dutasteride (given the in vitro ic50 values), then again, it hasn't been studied what actual doses of the 2 drugs are required *in vivo* to inhibit the 5-ar3 enzyme, we only have some research on that for the other two 5-ar enzymes.

But I would assume that the inhibition can't be *that* great with the standard doses of 1-5 mg finasteride and 0.1 - 0.5 mg dutasteride, because otherwise we should see a much higher drop in DHT levels from such a double (finasteride) or triple (dutasteride) inhibition, assuming that 5-ar3 is also producing DHT.

So hopefully, the low dose dutasteride I'm (and so many fellow male pattern baldness sufferers) are on, will continue to prevent any further Androgenetic Alopecia progression while not giving us diabetes and NAFLD.

Regards
Kaus Klinski

 

[Manochoice]

You guys seem like you're trying to talk yourselves into taking it... )

 

[Kaus Klinski]

Well, maybe we're doing ... kind of ;-)

Regards
Kaus Klinski

 

[NSix]

has there been any new studies on this?

i just ordered some duta but am hesitant about starting...

 

[Michael1986]

For what its worth, here's a recent study that has found that 5ar type 3 is present in human hair follicles:
https://link.springer.com/article/10.1007/s00403-017-1798-0.
The study was done on women with female pattern baldness, but I think we can assume that 5ar type 3 would most likely also be present in the hair follicles of men too.

I also found the following study that showed that 5ar type 3 converts testosterone to DHT:
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1349-7006.2007.00656.x.

So, if type 3 is present in the hair follicles, and if it also converts testosterone to DHT, the implication is that it plays a role in hair loss. It would be good if a study could be done to find out exactly what proportion of type 3 is inhibited by each of finasteride and dutasteride. Unfortunately, I don't think any study that answers this particular question has been done to date.

 

[Kaus Klinski]

Here are the IC50 values for both finasteride and dutasteride:

Enzyme IC50, mMa
Finasteride Dutasteride
SRD5a-1 106.9"17.1 8.7"0.4
SRD5a-2 14.3"2.7 57.0"6.8
SRD5a-3 17.4"1.4 0.33"0.02

As you can see, dutateride is muchmore potent in inhibiting 5-ar-3 (and1) than finasteride. The question remains, what daily dosage would be needed in vivo, AFAIK there is no research for that. But I think with the standard prostate dose (0.5 mg/day) almost all of the 5-ar2/3 enzyme activity would be inhibited (and about half o the 5-ar-1 activity, according to the information I have).

However, I don't think it is a good idea to inhibit anything else than the type 2 enzyme, because both type 1 and especially type 3 serve an important function within the cns/brain (synthesis of allopregnanolone).

Personally, I take 0.5 dutasteride eod orally and 0,1 mg topically once daily. I think this is the best compromise: it should inhibit virtually all type 2 5ar activity better and more constant thann finasteride due to the long half life (and, sadly, type 3, but finasteride at 1 - 5 mg/day would also inhibit type 3 to a high degree when I look at the ic50 values) while leaving most of the type 1 enzyme untouched.

And: dutasteride doesn't inhibit 5-beta-reductase at all, which is associated with glucose metabolism.

regards
Kaus Klinski

 

[Michael1986]

Here are the IC50 values for both finasteride and dutasteride:

Enzyme IC50, mMa
Finasteride Dutasteride
SRD5a-1 106.9"17.1 8.7"0.4
SRD5a-2 14.3"2.7 57.0"6.8
SRD5a-3 17.4"1.4 0.33"0.02

As you can see, dutateride is muchmore potent in inhibiting 5-ar-3 (and1) than finasteride. The question remains, what daily dosage would be needed in vivo, AFAIK there is no research for that. But I think with the standard prostate dose (0.5 mg/day) almost all of the 5-ar2/3 enzyme activity would be inhibited (and about half o the 5-ar-1 activity, according to the information I have).

However, I don't think it is a good idea to inhibit anything else than the type 2 enzyme, because both type 1 and especially type 3 serve an important function within the cns/brain (synthesis of allopregnanolone).

Personally, I take 0.5 dutasteride eod orally and 0,1 mg topically once daily. I think this is the best compromise: it should inhibit virtually all type 2 5ar activity better and more constant thann finasteride due to the long half life (and, sadly, type 3, but finasteride at 1 - 5 mg/day would also inhibit type 3 to a high degree when I look at the ic50 values) while leaving most of the type 1 enzyme untouched.

And: dutasteride doesn't inhibit 5-beta-reductase at all, which is associated with glucose metabolism.

regards
Kaus Klinski

You're good! You need to come here more often

 

[Kaus Klinski]

You're good! You need to come here more often

Thank you!

Well, I'm just trying to get along with the whole misery ... BTW, an englishman saying something nice to a german ... must be a rare occurence ;-)

regards
Kaus Klinski

 

[NSix]

Thank you!

Well, I'm just trying to get along with the whole misery ... BTW, an englishman saying something nice to a german ... must be a rare occurence ;-)

regards
Kaus Klinski

r u still on dutasteride? how long has it been?

if so, how is ur health?

do u know how effective .5 mg dutasteride EOD is?

 

[Kaus Klinski]

r u still on dutasteride? how long has it been?

if so, how is ur health?

do u know how effective .5 mg dutasteride EOD is?

Hi,
ad 1: yes, I'm still on dutasteride, I've been on it since 02/2015 (0.5 mg/day), about 2 years later I switched to E3d, then recently to eod. Been on finasteride prior to dutasteride since age 22 (40 now).

ad 2: my health is just fine.

ad 3: hard to tell, see the official "Zagallo" study results for a comparison:
http://www.pmda.go.jp/files/000220574.pdf

Notice: I'm on high dose TRT (350 mg T Enantate/week) and I want to prevent any BPH issues, so I use more than 0.1 mg dutasteride/day to keep my intraprostatic DHT levels as low as possible. For hair growth, I would assume that a dose of 0.1 mg dutasteride/day is more than sufficient, it should have a similar efficacy as ~5 mg finasteride/day while inhibiting the target enzyme (5-ar 2) more constantly due to the long half life. But this is mostly "bro science", nobody can tell exactly how effective it would be in each individual case.

regards
Kaus Klinski

 

[NSix]

Hi,
ad 1: yes, I'm still on dutasteride, I've been on it since 02/2015 (0.5 mg/day), about 2 years later I switched to E3d, then recently to eod. Been on finasteride prior to dutasteride since age 22 (40 now).

ad 2: my health is just fine.

ad 3: hard to tell, see the official "Zagallo" study results for a comparison:
http://www.pmda.go.jp/files/000220574.pdf

Notice: I'm on high dose TRT (350 mg T Enantate/week) and I want to prevent any BPH issues, so I use more than 0.1 mg dutasteride/day to keep my intraprostatic DHT levels as low as possible. For hair growth, I would assume that a dose of 0.1 mg dutasteride/day is more than sufficient, it should have a similar efficacy as ~5 mg finasteride/day while inhibiting the target enzyme (5-ar 2) more constantly due to the long half life. But this is mostly "bro science", nobody can tell exactly how effective it would be in each individual case.

regards
Kaus Klinski

when u transitioned from finasteride to dutasteride, did you taper off finasteride while taking dutasteride?

How's your hair at the moment?

Thank you for answering.

 

[Kaus Klinski]

No, for a couple of weeks I took both ~1,25 finasteride and 0.5 mg dutasteride a day until a my finasteride was all used up.

I lost a lot of hair during the 4 years off any treatment (between age 26 and 31 or so), but ever since starting treatment again, my hair loss has stabilized again.

Well, I'm a diffuse NW2-3A, so I have very little frontal hair left while having a full thick head of hair everywhere else. It looks really stupid in contrast, but what can I do.

regards
Kaus Klinski

 

[Dennis1775]

No, for a couple of weeks I took both ~1,25 finasteride and 0.5 mg dutasteride a day until a my finasteride was all used up.

I lost a lot of hair during the 4 years off any treatment (between age 26 and 31 or so), but ever since starting treatment again, my hair loss has stabilized again.

Well, I'm a diffuse NW2-3A, so I have very little frontal hair left while having a full thick head of hair everywhere else. It looks really stupid in contrast, but what can I do.

regards
Kaus Klinski

Look at my post 'Modelling and dutasteride' on my page Is it a life saver ? or a destroyer in some sense? increased fatigue? Definitely yes...
I am 21 years old at the moment norwood 1.5... Modelling in london and across europe But I am balding And I have been on the drug for the last 11 months It's unbelivable that I have no orgasms anymore Literally I have no orgasm sensitivity... Do you???

 

[NSix]

Look at my post 'Modelling and dutasteride' on my page Is it a life saver ? or a destroyer in some sense? increased fatigue? Definitely yes...
I am 21 years old at the moment norwood 1.5... Modelling in london and across europe But I am balding And I have been on the drug for the last 11 months It's unbelivable that I have no orgasms anymore Literally I have no orgasm sensitivity... Do you???

I've been on finasteride for 5 years. I have watery semen (so I'm assuming lower sperm count).

Aside from that, it's fine. No other sides that I feel to a meaningful degree.

I also don't think I'm benefiting from finasteride though.

Are you benefiting from dutasteride? Maybe try finasteride instead?

 

[NSix]

No, for a couple of weeks I took both ~1,25 finasteride and 0.5 mg dutasteride a day until a my finasteride was all used up.

I lost a lot of hair during the 4 years off any treatment (between age 26 and 31 or so), but ever since starting treatment again, my hair loss has stabilized again.

Well, I'm a diffuse NW2-3A, so I have very little frontal hair left while having a full thick head of hair everywhere else. It looks really stupid in contrast, but what can I do.

regards
Kaus Klinski

Thanks Kaus.

One thing though: weren't you worried about losing your gains or stabilization from finasteride by dropping it after a few weeks? dutasteride doesn't work right away does it?

Would it be better to taper off finasteride while transitioning?

I was thinking if I were to transition to dutasteride, I would take them both until about 6 months (slowly coming off of finasteride by month 6).

 

[Kaus Klinski]

Literally I have no orgasm sensitivity... Do you???

Nothing different with my orgasms ... but notice that I'm on high dose TRT, so my T levels are probably at least 3 times higher than yours, even though you're half my age ;-).

Regards
Kaus Klinski

 

[Kaus Klinski]

I was thinking if I were to transition to dutasteride, I would take them both until about 6 months (slowly coming off of finasteride by month 6).

I don't see any problems with that, but on the other hand, I don't think it's necessary to take both drugs concomitantly for such a long period of time. If I hadn't had the finasteride in the house anyway (and I wanted to use it up rather than throwing it away), I would have made the switch right away. I wasn't worried about losing my finasteride gains. Dutasteride lowers DHT levels after taking the very first dose, but it's true that for steady state levels to establish it would take roughly five half lifes (about 6 months), but that doesn't mean it won't reduce DHT levels much sooner. Anybody please correct me if I'm wrong.

regards
Kaus Klinski

Btw please excuse my rather imperfect english, I haven't used it for many years and I'm much much better in reading/understanding than actually speaking/writing english

 

[Michael1986]

I initially used finasteride very briefly before switching to dutasteride. I switched straight from finasteride to dutasteride. I used a loading dose of dutasteride for the first ten days to build it up in my system. I took 1.5mg each day for these first ten days, and then 0.5mg a day from then on. Other people on these forums have done this too when starting dutasteride. I've now been using 0.5mg dutasteride for over five years with great success.