I know that Topical spironolactone has a half-life around 12 hours, but what is it's "activity life". I assume by half-life they are referring to how long it remains free in the target tissue. My question is, once it binds, how long does it stay bound to the AR on the follicle? Anyone got info on this? I know finasteride has about the same half-life, but it remains bound to the 5ar enzyme for quite a bit longer than it's half-life shows.
Topical spironolactone question
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George Costanza
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Good question, let me email dr.lee.
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douggie said:
Where on earth did you hear THAT?? I don't think anybody knows what that figure is! I don't recall ever seeing an estimate of that in any medical literature.
douggie said:
Finasteride is considered to be an IRREVERSIBLE inhibitor of the 5a-reductase enzyme: once it's bound, that enzyme molecule is KAPUT forever!
Bryan
I thought I read it on Dr. Lee's site, that would be why you would want to put it on 12 hours apart.
I know finasteride is a suicide inhibitor, but eventually your body will plop out more 5ar for test to bind to. The thing is, if the spironolactone binded to the AR of the follicle permanently, you would not need to use it more than a couple times in your life or a couple times per hair growth cycle. Since we know this to be not true, I was wondering what we could expect in terms of how long it does stay attached in order to dose correctly.
I know finasteride is a suicide inhibitor, but eventually your body will plop out more 5ar for test to bind to. The thing is, if the spironolactone binded to the AR of the follicle permanently, you would not need to use it more than a couple times in your life or a couple times per hair growth cycle. Since we know this to be not true, I was wondering what we could expect in terms of how long it does stay attached in order to dose correctly.
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douggie said:
If you can find that statement and quote it or provide a link to it, I'd greatly appreciate it! I doubt that he really said anything like that (unless he was just speculating), because I really don't think there's any justification for it in the medical literature.
douggie said:
Ummm....probably just the OPPOSITE of that! The study below found that androgenic stimulation (testosterone) UPREGULATES the production of 5a-reductase type 2 in human hair follicles, meaning that the opposite situation (reducing androgenic stimulation) should DOWNREGULATE it!
"RNA-Levels of 5a-Reductase and Androgen Receptor in Human Skin, Hair Follicles and Follicle-Derived Cells", Eicheler et al, in the book "Hair Research for the Next Millenium", 1996.
douggie said:
WHAT??? Let me explain something to you: there is a CONSTANT, continuous production of androgen receptors within cells! Even if you had an antiandrogen permanently bound to a given set of receptors, you would STILL have to supply that antiandrogen on a regular basis, just to take care of the newly-synthesized ones.
(BTW, just for your information, the turnover rate of androgen receptors is on the order of a day or two, according to one study I've read.)
Bryan
Bryan said:
Do you have a source for this last bit of info, it is highly interesting to me. Also, I am assuming that source you provided was based on an experiment of some sort? Did they inject testosterone or DHT into the subjects and test the results? Just wondering because testosterone by itself is not all that powerful of an androgen when compared to DHT.
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douggie said:
Sorry, I didn't write down the article where that came from. If I see a similar statement again, I'll make a note of the reference.
douggie said:
It was an in vitro experiment using cultured human scalp hair follicles.
douggie said:
Doesn't really make any difference. The point is that androgenic stimulation UPregulated 5a-reductase type 2. An even stronger stimulus like DHT very likely would have been an even STRONGER stimulus for upregulation.
Bryan
George Costanza
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Well I emailed Dr. Lee and got a response from the Doctor himself. I pasted my questions and his answer below.
What's the half life on 5% spironolactone and how long does it stay bound to the androgen receptor site of the hair follicle?
Spironolactone metabolizes rapidly in the skin and remains effective for up to 12 hours. There are three distinct benefits of topical spironolactone in the treatment of male pattern baldness:
(1). Spironolactone significantly reduces the amount of DHT in the scalp by inhibiting the conversion of precursor steroids to DHT.
(2). Spironolactone reduces the DHT in the scalp by converting localized testosterone into estrogen, which is thought to be protective of the hair follicles.
(3). Spironolactone blocks the follicular androgen receptor sites, thereby rendering any residual or circulating DHT harmless to the hair follicles. Rather than reducing the levels of circulating (serum) DHT like finasteride does, it prevents DHT from making a complex with the androgen receptor protein.
Also, how good are the chances of the drug to actually reach the follicle if you fully rub the 5% lotion into the scalp completely?
As with any topical medication, only those molecules of the medication directly adjacent to the skin are absorbed. So, it's a waste to apply 'a thick goop' to the scalp. A thin film of 5% lotion of spironolactone is sufficient to decrease DHT in the scalp and to block the androgen receptor sites. It is not necessary to "fully rub the lotion into the scalp."
And would the 2% solution absorb better?
Liquids penetrate better and more rapidly than lotions. However, the lotion has a greater concentration of spironolactone and does not have an odor.
Best wishes,
Richard Lee, M.D.
What's the half life on 5% spironolactone and how long does it stay bound to the androgen receptor site of the hair follicle?
Spironolactone metabolizes rapidly in the skin and remains effective for up to 12 hours. There are three distinct benefits of topical spironolactone in the treatment of male pattern baldness:
(1). Spironolactone significantly reduces the amount of DHT in the scalp by inhibiting the conversion of precursor steroids to DHT.
(2). Spironolactone reduces the DHT in the scalp by converting localized testosterone into estrogen, which is thought to be protective of the hair follicles.
(3). Spironolactone blocks the follicular androgen receptor sites, thereby rendering any residual or circulating DHT harmless to the hair follicles. Rather than reducing the levels of circulating (serum) DHT like finasteride does, it prevents DHT from making a complex with the androgen receptor protein.
Also, how good are the chances of the drug to actually reach the follicle if you fully rub the 5% lotion into the scalp completely?
As with any topical medication, only those molecules of the medication directly adjacent to the skin are absorbed. So, it's a waste to apply 'a thick goop' to the scalp. A thin film of 5% lotion of spironolactone is sufficient to decrease DHT in the scalp and to block the androgen receptor sites. It is not necessary to "fully rub the lotion into the scalp."
And would the 2% solution absorb better?
Liquids penetrate better and more rapidly than lotions. However, the lotion has a greater concentration of spironolactone and does not have an odor.
Best wishes,
Richard Lee, M.D.
JesusFreak
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Topical spironolactone looks like the perfect treatment on paper. Must be why I grew so much hair while using Dr. Lee's 2% alone as a single agent. I grew enough hair while using it that it shocked the girl who cuts my hair. It's given me better results than propecia in just 3 months...Guess I'm just lucky.
BTW, I apply it 1X/day. Also, I didn't feel like the 5% cream version worked as well as the 2% alcohol version.
BTW, I apply it 1X/day. Also, I didn't feel like the 5% cream version worked as well as the 2% alcohol version.
Bryan said:
So here is my question. More testosterone will cause an upregulation of 5ar2 in the hair follice. Isn't this precisely what happens when you take finasteride, your body will have more circulating test since less is converted to DHT? I can't remember where I read it, but I believe the increase is on the order of a 15% increase. That is, of course, if it does not convert to estrogen. Is DHT a player here in the androgenic stimulation picture since it is more androgenic than testosterone or does this possibly throw support to the notion that there are other mechanisms by which finasteride works?