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Topic Title: Miconazole inhibits T better than Ketoconazole...
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Created On: 10/22/2010 05:25 PM
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 10/22/2010 05:25 PM
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RSR38
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Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals. Kjærstad MB, Taxvig C, Nellemann C, Vinggaard AM, Andersen HR.

Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, JB Winsløwsvej 17, DK-5000 Odense C, Denmark.

Abstract Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, prochloraz) were more potent than the triazoles (epoxiconazole, propiconazole, tebuconazole). The critical mechanism seems to be disturbance of steroid biosynthesis. In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazole approximately miconazole>ketoconazole>tebuconazole>epoxiconazole>propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase inhibition, since they inhibited the response induced by both 17beta-estradiol (miconazole>econazole approximately ketoconazole>prochloraz>tebuconazole>epoxiconazole>propiconazole) and testosterone (econazole>miconazole>prochloraz>ketoconazole>tebuconazole>epoxiconazole>propiconazole). The triazoles were anti-androgenic in an androgen receptor reporter gene assay (epoxiconazole approximately tebuconazole>propiconazole). This effect could not be evaluated for the pharmaceutical imidazoles due to cytotoxicity.


I think the Micon is helping me and I suspect it is partially blocking the extra T in scalp, complimenting the Finasteride Dht suppression. Looks like Miocon IS stronger than Keto after all....
 10/22/2010 06:29 PM
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DecadeTwo
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Originally posted by: RSR38

In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone.


So, besides being AR Receptor antagoinists, the azole derivatives also block hormone metabolism (like Fin and 5ar)...

Originally posted by: RSR38

I think the Micon is helping me and I suspect it is partially blocking the extra T in scalp, complimenting the Finasteride Dht suppression. Looks like Miocon IS stronger than Keto after all....


... isn't this not quite the same thing as affinity for the AR?


Here's something interesting I found:


Ketoconazole binds to the human androgen receptor.

Eil, C

Ketoconazole, an imidazole anti-fungal agent, has often produced features of androgen deficiency including decreased libido, gynecomastia, impotence, oligospermia, and decreased testosterone levels, in men being treated for chronic mycotic infections. Based on these potent effects on gonadal function in vivo as well as previous work in vitro demonstrating affinity of ketoconazole for receptor proteins for glucocorticoids and 1,25(OH)2 vitamin D3 and for sex steroid binding globulin (SSBG), the binding of ketoconazole to human androgen receptors (AR) in vitro was also examined. Ketoconazole competition with [3H]methyltrienolone (R1881) for androgen binding sites in dispersed, intact cultured human skin fibroblasts was determined at 22 degrees C. Fifty percent displacement of [3H]R1881 binding to AR was achieved by 6.4 +/- 1.8 (SE) x 10(-5) M ketoconazole. Additional binding studies performed with ketoconazole in the presence of increasing amounts of [3H]R1881 showed that the interaction of ketoconazole with AR was competitive when the data were analyzed by the Scatchard method. It should be noted, however, that the dose of ketoconazole required for 50% occupancy of the androgen receptor is not likely to be achieved in vivo, at least in plasma. Finally, androgen binding studies performed with other imidazoles, such as clotrimazole, miconazole, and fluconozole, revealed that in this class of compounds only ketoconazole appears to interact with the androgen receptor. Ketoconazole appears to be the first example of a non-steroidal compound which binds competitively to both SSBG and multiple steroid hormone receptors, suggesting that the ligand binding sites of these proteins share some features in common.

Horm-Metab-Res. 1992 Aug; 24(8): 367-70


So it seems safe to say that M will lower T better than K, but K will actually prevent both DHT and T from binding to the AR.

This also seems to answer the question I've been raising since the M vs K question was brought up: why is it that K is commonly used for androgen modulated conditions, such as Prostate Cancer and AGA, but M isn't?

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NW < 2 since 1999

The plural of 'anecdote' is not 'evidence'.
--Alan I. Leshner

Correlation does not imply causation.
--Logic

When you believe in things that you don't understand then you suffer. Superstition ain't the way.
--Stevie Wonder

I'm not an MD, and I'm not a hair loss expert.

Edited: 10/22/2010 at 07:06 PM by DecadeTwo
 10/22/2010 10:34 PM
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getsome
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Thanks guys, but am I missing something or why is it, if true, that M makes women's hair grow so much *faster* than normal?
 10/22/2010 11:17 PM
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Thyroids
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Interesting...Always thought testosterone was not harmful to hair.
 10/22/2010 11:25 PM
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RSR38
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Decade is da bomb! great info as usual!
 10/23/2010 06:34 AM
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RSR38
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Decade...

You think alternating with Nizoral and Micon would be beneficial, then, since they appear to work through some different mechanisms? Like Micon once daily and Nizoral 2x daily since it has a shorter half life apparently. I am reading that Micon has a 24 hour half life and Niz is 8 hours...
 10/23/2010 08:54 AM
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cliquesh
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Originally posted by: RSR38

Decade...



You think alternating with Nizoral and Micon would be beneficial, then, since they appear to work through some different mechanisms? Like Micon once daily and Nizoral 2x daily since it has a shorter half life apparently. I am reading that Micon has a 24 hour half life and Niz is 8 hours...


I would imagine, from the information above, the only reason why Nizoral is effective is because it is an AR receptor blocker, which is something Micon doesn't do. Micon only reduces your T levels, which are produced in your testies and adrenal glands, and I seriously doubt enough micon or nizoral is systematical absorbed to affect those two organs.

Edited: 10/23/2010 at 09:00 AM by cliquesh
 10/23/2010 09:06 AM
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nyhair19
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Could you possibly use M in conjunction with K to enhance the effect of both of them?

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Jan 08 - Present
Fin 1mg/daily, .5mg 1-2x/week (Aug 13), 1/mg daily (14)
Minox 5% (Oct 11)
Pygeum, Nettle Root, SawP 2x, Fish oil, Peppermint Tea
Tricomin/Folligen
Hair Cycle Shampoo(08-11), Niz, Regenepure(2011)
Contemplating RU (Aug 14)
 10/23/2010 10:54 AM
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Harry Balls
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Originally posted by: RSR38

Decade...



You think alternating with Nizoral and Micon would be beneficial, then, since they appear to work through some different mechanisms? Like Micon once daily and Nizoral 2x daily since it has a shorter half life apparently. I am reading that Micon has a 24 hour half life and Niz is 8 hours...


The systemic halflife of nizoral is irrelevent. It's effects in the scalp last a few days. So daily use is not necessary.

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 10/23/2010 12:55 PM
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grove
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Originally posted by: RSR38


I think the Micon is helping me and I suspect it is partially blocking the extra T in scalp, complimenting the Finasteride Dht suppression. Looks like Miocon IS stronger than Keto after all....


So would using Micon affect you systematically or just topically. I cant take any more sides as Fin is killing me.

Plus side of Micon is how easy it is to get.

I had to get Keto from ebay from India. Its called Nizral. supposedly from Johnson and Johnson. But we all question how legit drugs from India can be. But Micon is super easy to pick up. If anyone knows how to get 2% Keto cream from US, let me know
 10/24/2010 10:02 AM
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DecadeTwo
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Originally posted by: RSR38

Decade...

You think alternating with Nizoral and Micon would be beneficial, then, since they appear to work through some different mechanisms?


Probably, but I think topical Spiro would be a better addition to the average regimen.

-------------------------
NW < 2 since 1999

The plural of 'anecdote' is not 'evidence'.
--Alan I. Leshner

Correlation does not imply causation.
--Logic

When you believe in things that you don't understand then you suffer. Superstition ain't the way.
--Stevie Wonder

I'm not an MD, and I'm not a hair loss expert.
 10/25/2010 06:21 PM
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RSR38
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Ok about the Spiro, but let me ask why is Ketocoazole SAHAMPOO part of the "Big 3"? Instead of it being Fin/Dut, Minox, and Keto shampoo, why wouldn't it have panned out to be Fin, Min, and Spiro? If Keto shampoo is the standard, it would seem like the Keto and Micon cream would be much better than the shampoo. I really see FEW success stories about Spiro, even if it appears better on paper. Just thinking.
 10/25/2010 08:21 PM
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Harry Balls
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A few reasons. It is a mild antiandrogen and possible growth stimulant. I personally suspect it works more as a growth stimulant... at least topically. There is a study that compared its effects to 1x daily application 2% minoxidil. Cumulatively with the rest of the big three, this is significant and justifies it being a staple for fighting hair loss.

It mays also help the other drugs work better by controlling sebuderm. In the propecia clinical trials, the volunteers were prescribed t-gel for the same reason.

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 10/25/2010 09:03 PM
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RSR38
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I know that about keto shampoo... What I am saying is why isn't everyone using the CREAM instead? It would seem much more logical and effective compared to a shampoo with the same ingredient.

The point I was making about Spiro was in reference to what Decade said.
 10/25/2010 09:36 PM
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getsome
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A mild antiandrogen and a stimulant about as potent as 2% minoxidil? Correct me if Im wrong but isnt 2% minox just a bit more effective than water? Seriously! IVe been on 5% for years and it has most certainly helped maintain, but it has hardly been a miracle for anyone so far as I know... and thats 5%!
 10/25/2010 10:30 PM
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DecadeTwo
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Originally posted by: getsome

A mild antiandrogen and a stimulant about as potent as 2% minoxidil? Correct me if Im wrong but isnt 2% minox just a bit more effective than water?


Pretty sure you're wrong about that.

Originally posted by: getsome Seriously! IVe been on 5% for years and it has most certainly helped maintain, but it has hardly been a miracle for anyone so far as I know... and thats 5%!


Minoxidil is from 1984. It doesn't maintain hair at all. After 16 weeks or so you should know what it is or isn't doing for you.

On the bright side, some people regrow a ton of hair with minox, and unlike 1984 we have antiandrogens that can maintain that regrowth.


Originally posted by: RSR38

Ok about the Spiro, but let me ask why is Ketocoazole SAHAMPOO part of the "Big 3"? Instead of it being Fin/Dut, Minox, and Keto shampoo, why wouldn't it have panned out to be Fin, Min, and Spiro? If Keto shampoo is the standard, it would seem like the Keto and Micon cream would be much better than the shampoo. I really see FEW success stories about Spiro, even if it appears better on paper. Just thinking.


I suspect it's simply because we have a ton of studies showing that Ketoconazole is effective for AGA, and much fewer when it comes to Spiro.

Also, minoxidil is FDA approved, and as far as Nizoral: people need to use shampoo anyway.

Spro is just a funky smelling cream that most people wouldn't want to deal with.

On the other hand, spiro is more commonly used off-label topically for other androgen modulated disorders such as hirsutism and acne vulgaris (despite the smell), while keto is not, so it doesn't take a huge deductive leap to realize that spiro competes better for the AR.

I bet that in a head to head study sprio would prove better than keto shampoo.

Can someone scour pubmed to find evidence for or against this?

Bryan could fill in the blanks on this one better than I could.

-------------------------
NW < 2 since 1999

The plural of 'anecdote' is not 'evidence'.
--Alan I. Leshner

Correlation does not imply causation.
--Logic

When you believe in things that you don't understand then you suffer. Superstition ain't the way.
--Stevie Wonder

I'm not an MD, and I'm not a hair loss expert.

Edited: 10/25/2010 at 10:40 PM by DecadeTwo
 10/25/2010 10:52 PM
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woodly
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i was thinking of combining MN and nizoral cream and applying it every night. would these work fine as a mixture? also would every night too much?
 10/25/2010 10:56 PM
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DecadeTwo
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I'd say that you should consider mixing the K cream with Spiro instead.

So what if M reduces T better than K? We don't even know how harmful T is beyond it's propensity to be metabolized into DHT.

Ultimately, if you stop the androgen from binding to the receptor than you've achieved what you want to achieve, and the study I cited above shows that K and Sprio will do that, but M wont.

Originally posted by: Thyroids

Interesting...Always thought testosterone was not harmful to hair.


I've heard of an in vitro study that was suggestive, but we really don't know how exacerbating T is in itself in vivo.

Personally, I'm much more worried about DHT first, and preventing T from binding to the AR is secondary to me.

Remember, pseudoherms never develop AGA because they have no 5ar Type II, and despite having more T than the average male.

-------------------------
NW < 2 since 1999

The plural of 'anecdote' is not 'evidence'.
--Alan I. Leshner

Correlation does not imply causation.
--Logic

When you believe in things that you don't understand then you suffer. Superstition ain't the way.
--Stevie Wonder

I'm not an MD, and I'm not a hair loss expert.
 10/26/2010 01:19 AM
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Bryan
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Originally posted by: getsome

Correct me if Im wrong but isnt 2% minox just a bit more effective than water?


I'm baffled as to why you would make such an odd, sarcastic remark about 2% topical minoxidil! A really excellent study by a well-known hairloss researcher answered the question extremely well of how do the two versions (2% and 5%) compare in effectiveness: "Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment". Vera H. Price et al, J Am Acad Dermatol 1999;41:717-21.

For a full 96 weeks, they applied the two versions of topical minoxidil to their test subjects, along with separate groups that got either a placebo solution without any minoxidil, or no treatment at all. Every six weeks for the duration of the study, they carefully measured hair counts and hair weights in all four of the groups. Here are the results after 96 weeks of treatment:

The 2% minoxidil group had hair counts that were about 68.4% as good as the 5% minoxidil group (as an improvement over the placebo/no-treatment groups).

The 2% minoxidil group had hair weights that were about 77.4% as good (!!) as the 5% minoxidil group (as an improvement over the placebo/no-treatment groups).

I obtained those figures not just by looking at the graphs provided by the study and estimating them, but by carefully applying a ruler to the graphs and measuring them directly. So there you have it! It's perfectly clear that 2% minoxidil is nearly as effective as 5% minoxidil. I don't know why that word hasn't filtered down to some people yet!
 10/26/2010 08:01 AM
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getsome
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Alright, I guess I stand corrected, but its still weaker than 5%... And I guess my point is, 5% is no cure.

As far as minox not maintaining, I quit it for about 6 months a while ago and it was a mistake.. I lost some ground. It never, however, had any major regrowth from it , even after years of use. Whatever you want to call that, it sure seemed like it was maintaing some percentage of hair to me- not growing more hair than baseline.
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