The possibility of 3 alpha-hydroxysteroid dehydrogenase (HSD) as an alternative to finasteride + even more detailed information on fin side effects

[Matt Skiba]

This is actually an enzyme found naturally in the human body, kinda like 5-alpha reductase, I guess you could call it the anti 5-alpha reductase because instead of converting Testosterone to DHT, it converts DHT back to testosterone, I also understand that by inhibiting 5-alpha reductase, testosterone and lieutinizing hormone production is raised via the negative feedback loop of the hypothalamic-pituitary-testicular axis (HPTA). For those of you who don't know what the HPTA is, basically it is the system by which your hypothalamus gland in the brain senses the amount of androgens and estrogens in your body and sends a chemical signal accordingly to the pituitary gland, which sends a chemical signal to your testicles telling it the amount of hormones to produce. If the hypothalamus detects less DHT in the blood, your balls start producing more testosterone to make up for it, this could have possible negative consequences. One possibility which is a fact and does happen for some people is that the excess testosterone gets converted to estrogen via the aromatase enzyme and this causes such problems as ED and gynocomastia. Also, keep in mind that aromatase levels rise when there is less 5-alpha reductase. I think another possibility is your balls can't handle the excess workload so they shut down, even another possibility is that for some people waaay too much testosterone is made, and this creates an excess negative feedback in the hypothalamus, so your body shuts down and creates a much smaller amount of androgens and goes into a hypogonadal state, similar to that experienced by body-builders who've abused anabolic steroids.

 

The enzyme CYP3A4 which is found in the liver is what's responsible for metabolizing and getting rid of finasteride (among many other drugs) in the body. I feel that for some people who ingest certain things that inhibit this enzyme it makes them more likely to get side effects. I believe the most common of these substances would be red wine and grapefruit juice, but oddly enough the list also includes ketoconazole (nizoral). So basically if you inhibit this enzyme, you could be getting a mega-dose of finasteride since your body isn't able to fully metabolize it. You can see a list of substances in the following wikipedia link.

http://en.wikipedia.org/wiki/CYP3A4

 

Now lets talk about 3 alpha-hydroxysteroid dehydrogenase, often times referred to as 3-alpha HSD. This enzyme acts by converting DHT back to testosterone, and also has some other roles that I think involve progesterone, pregnenolone, and allopregnenolone, but I am not very sure of the details on this, what I do know though is that it doesn't inhibit the effects of the conversion of progesterone to allopregnenolone like finasteride does, but instead it is an enzyme, like 5-alpha reductase, that also converts progesterone to allopregnenolone, so any neurotoxic effects are avoided, and may even be ameliorated as there is more allopregnenolone being produced. I believe HSD is found in heavy concentrations in muscular tissue, and is the reason that DHT has no anabolic muscular effect.

 

Now... correct me if I'm wrong, though DHT may be a much more powerful activator of an androgen receptor than testosterone, I have read that it pretty much has the same level of interaction with the hypothalamus as testosterone, so if you are converting DHT back to testosterone, you are not messing with the HPTA and you are avoiding adverse endocrine effects. Of course reducing DHT could have negative consequences of it's own, but I believe that with HSD it wouldn't be too hard to play around with dosages to find a healthy amount so there is sufficient DHT to maintain reproductive tissue and sperm, as well as libido, and be able to stop as much hair loss as possible with as little side effects as possible.

http://www.jbc.org/cgi/content/full/276/45/42091

 

HSD is of course a natural thing found within the body, and for this reason, the FDA would never approve it for anything. So it would have to be sold as a supplement. I could imagine that it could be expensive, and possibly not easy to synthesize and manufacture. But I'm sure that it could be sold. I'm actually surprised that someone isn't already doing this, I'm sure there's some sort of reasoning behind it though. I would be very interested to find out why.

 

In any case I would love to hear what someone else thinks of this, as long as I'm not labeled as being crazy, a fear-mongerer, or a hypochondriac.

[Matt Skiba]

This is actually an enzyme found naturally in the human body, kinda like 5-alpha reductase, I guess you could call it the anti 5-alpha reductase because instead of converting Testosterone to DHT, it converts DHT back to testosterone, I also understand that by inhibiting 5-alpha reductase, testosterone and lieutinizing hormone production is raised via the negative feedback loop of the hypothalamic-pituitary-testicular axis (HPTA). For those of you who don't know what the HPTA is, basically it is the system by which your hypothalamus gland in the brain senses the amount of androgens and estrogens in your body and sends a chemical signal accordingly to the pituitary gland, which sends a chemical signal to your testicles telling it the amount of hormones to produce. If the hypothalamus detects less DHT in the blood, your balls start producing more testosterone to make up for it, this could have possible negative consequences. One possibility which is a fact and does happen for some people is that the excess testosterone gets converted to estrogen via the aromatase enzyme and this causes such problems as ED and gynocomastia. Also, keep in mind that aromatase levels rise when there is less 5-alpha reductase. I think another possibility is your balls can't handle the excess workload so they shut down, even another possibility is that for some people waaay too much testosterone is made, and this creates an excess negative feedback in the hypothalamus, so your body shuts down and creates a much smaller amount of androgens and goes into a hypogonadal state, similar to that experienced by body-builders who've abused anabolic steroids.

 

The enzyme CYP3A4 which is found in the liver is what's responsible for metabolizing and getting rid of finasteride (among many other drugs) in the body. I feel that for some people who ingest certain things that inhibit this enzyme it makes them more likely to get side effects. I believe the most common of these substances would be red wine and grapefruit juice, but oddly enough the list also includes ketoconazole (nizoral). So basically if you inhibit this enzyme, you could be getting a mega-dose of finasteride since your body isn't able to fully metabolize it. You can see a list of substances in the following wikipedia link.

http://en.wikipedia.org/wiki/CYP3A4

 

Now lets talk about 3 alpha-hydroxysteroid dehydrogenase, often times referred to as 3-alpha HSD. This enzyme acts by converting DHT back to testosterone, and also has some other roles that I think involve progesterone, pregnenolone, and allopregnenolone, but I am not very sure of the details on this, what I do know though is that it doesn't inhibit the effects of the conversion of progesterone to allopregnenolone like finasteride does, but instead it is an enzyme, like 5-alpha reductase, that also converts progesterone to allopregnenolone, so any neurotoxic effects are avoided, and may even be ameliorated as there is more allopregnenolone being produced. I believe HSD is found in heavy concentrations in muscular tissue, and is the reason that DHT has no anabolic muscular effect.

 

Now... correct me if I'm wrong, though DHT may be a much more powerful activator of an androgen receptor than testosterone, I have read that it pretty much has the same level of interaction with the hypothalamus as testosterone, so if you are converting DHT back to testosterone, you are not messing with the HPTA and you are avoiding adverse endocrine effects. Of course reducing DHT could have negative consequences of it's own, but I believe that with HSD it wouldn't be too hard to play around with dosages to find a healthy amount so there is sufficient DHT to maintain reproductive tissue and sperm, as well as libido, and be able to stop as much hair loss as possible with as little side effects as possible.

http://www.jbc.org/cgi/content/full/276/45/42091

 

HSD is of course a natural thing found within the body, and for this reason, the FDA would never approve it for anything. So it would have to be sold as a supplement. I could imagine that it could be expensive, and possibly not easy to synthesize and manufacture. But I'm sure that it could be sold. I'm actually surprised that someone isn't already doing this, I'm sure there's some sort of reasoning behind it though. I would be very interested to find out why.

 

In any case I would love to hear what someone else thinks of this, as long as I'm not labeled as being crazy, a fear-mongerer, or a hypochondriac.

[calvinmd]

I think it reads like some decent suggestions, but I think maybe it suffers from a little of the "pro-natural bias" at the expense of real results in several places.

 

 

They at least alluded to the idea of Saw Palmetto rather than Finasteride. Nice try, but SP's known prostate benefits don't transfer to MPB results anywhere near as well.

 

That aspect of SP is pretty well known among the hair loss community. So whenever I read someone suggesting SP for hair loss, I immediately begin to suspect that I'm listening to a writer who doesn't know much about hair loss but they're pretty sure they can dig up a "natural" alternative to anything made by the pharmaceutical industry. It makes me think the source is more biased than informed.

 

 

The stuff about naturally manipulating 5-alpha-reductase is interesting. However, I'm not sure I see the big benefit. The side effects & problems from DHT inhibition seem to primarily come from the DHT inhibition itself, not anything else in the process. So I suppose a natural alternative might work to spare your liver some amount of processing issues, but I doubt it's actually gonna have fewer side effects for a given amount of hair loss. It sounds like another case of a natural alternative that's good to know, but probably doesn't offer any real seat-of-the-pants improvement over the existing pharmaceutical option.

 

 

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[Matt Skiba]

Originally posted by calvinmd:

The side effects & problems from DHT inhibition seem to primarily come from the DHT inhibition itself, not anything else in the process. So I suppose a natural alternative might work to spare your liver some amount of processing issues, but I doubt it's actually gonna have fewer side effects for a given amount of hair loss. It sounds like another case of a natural alternative that's good to know, but probably doesn't offer any real seat-of-the-pants improvement over the existing pharmaceutical option.

 

 

For the record I am not talking about saw palmetto in my post, I am talking about the naturally occuring enzyme 3 alpha-hydroxysteroid dehydrogenase.

 

And as for your comment about side effects coming primarily from DHT inhibition itself, that is very untrue.

 

I think for most people side effects come from the elevated level of estrogen in the body which is caused by the inhibition of DHT. DHT itself may have some reproductive function, but having a lowered amount of it usually doesn't do too much bad.

 

You might want to reread my post a bit more carefully, because I don't want to repeat myself.

 

Basically my theory is that by utilizing the HSD enzyme, someone won't end up with as much of an elevated testosterone level as they do with the use of finasteride, and because of this less excess testosterone will be converted to estrogen via the aromatase enzyme.

 

Can you explain to me how gynocomastia(titties) happens by only having a lower amount of DHT?

 

You can't.

 

Estrogen is the culprit.

[calvinmd]

Chill man. You asked for responses.

 

When I referred to "a writer who doesn't know much about hair loss" etc, I wasn't intending to refer to you. I meant that was my immediate reaction to the article that you linked to. (I'm sorry if that accidentally came off like I was picking on you rather than the article's author.)

 

 

 

With regards to Fin, I also didn't mean that a lack of DHT itself is the culprit of the side effects. I meant to say that the main function of Fin (lowering DHT, and the subsequent rise in estrogen that it generally causes) was causing the side effects. I totally agree that the estrogen increase probably has more to do with the side effects than anything else.

 

I re-read what you posted and I think I understood it better this time. I can see why it's an interesting idea; it sounds like potentially a way to create an alternative version of "finasteride" that converts the excess DHT into more testosterone rather than estrogen.

 

I'm not sure whether that's entirely the greatest idea either, at least when used alone. (Testosterone can be overdone, too.) But I could definitely imagine that using some combination of Finasteride and this other stuff might work to produce a much more properly-balanced hormonal system than the Finasteride alone is capable of doing.

 

It's interesting, and it might really bear looking into.

 

 

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