Does Ketoconazole Block Dht Systemically Or Only In The Follicles?

[Dimitri001]

I understand the mechanism is that it binds to androgen receptors, but does it do this only at the follicle or systemically? Since stuff can get into blood through the follicles, I assume it goes systemic.

EDIT: I'm talking about topical application, not oral.

 

[Kambrira159]

It can go systemic like anything else.

 

[Dimitri001]

It can go systemic like anything else.

Is that an assumption or have you read something that suggests so?

 

[Kambrira159]

Is that an assumption or have you read something that suggests so?

Based on what is written on the drug from certain health sites.

 

[tomJ]

It def goes systemic. I get sides from it now. Didnt in my younger years but anti androgens caught up to me.

 

[cyclonus]

Most studies say *azoles* absorb poorly from the skin to the bloodstream, so i wouldn't be worried. It also doesn't cross the blood-brain-barrier.
https://www.ncbi.nlm.nih.gov/pubmed/3280211



But Ketoconazole oral is a real beast with much worse sides than finasteride or dutasteride.

 

[Dimitri001]

Based on what is written on the drug from certain health sites.

Can you post a link? Because I've seen a study where they failed to find it in the blood of people who were using it in a shampoo for a prolonged time (several months). In one study they found it in blood, but it was used on children who had some kind of skin issue, so their skin might have been more permeable and they were applying it to 50%+ of their skin.

To be clear, I'm wondering whether it goes systemic if applied topically, not orally. And it would be ideal if there are studies of it applied to scalp, because things may get absorbed more readily through hair follicles, rather than just skin.

It def goes systemic. I get sides from it now. Didnt in my younger years but anti androgens caught up to me.

Are you talking about oral k or in a shampoo?
What kind of sides do you get?
Are you using anything else that screws with hormones?

 

[tomJ]

Can you post a link? Because I've seen a study where they failed to find it in the blood of people who were using it in a shampoo for a prolonged time (several months). In one study they found it in blood, but it was used on children who had some kind of skin issue, so their skin might have been more permeable and they were applying it to 50%+ of their skin.

To be clear, I'm wondering whether it goes systemic if applied topically, not orally. And it would be ideal if there are studies of it applied to scalp, because things may get absorbed more readily through hair follicles, rather than just skin.



Are you talking about oral k or in a shampoo?
What kind of sides do you get?
Are you using anything else that screws with hormones?

Hey mam I'm a bit reluctant to mention my sides because many will say im crazy or whatever. I'll start off by saying I used nizoral for years with absolutely no problems. I also took finasteride off and on but always had to quit due to sides. Well the last round of finasteride messed me up bad amd ever since then I get sides when using keto shampoo. About 12 hours after using keto shampoo I get fatigue and my blood pressure drops a bit. I feel sick amd sometimes nausea. I even get chest pains. I'm thinking it messes with my adrenal glands but I'm no doctor. I almost went to the hospital a few times as my heart rate became very shallow and uncomfortable to the point I was sweating like I had a weak heart. I know this sounds nuts but for me it def goes systemic.....oh yea it also makes my heart flutter and skip beats....but like I said, I used it for years with no problems. It wasnt til the bad finasteride crash that this happened.

 

[jamesbooker1975]

Most studies say *azoles* absorb poorly from the skin to the bloodstream, so i wouldn't be worried. It also doesn't cross the blood-brain-barrier.
https://www.ncbi.nlm.nih.gov/pubmed/3280211



But Ketoconazole oral is a real beast with much worse sides than finasteride or dutasteride.

that study are not done in a chronic way . Shampoo should be safe , not sure about chronic use of lotion or cream .

 

[Dimitri001]

that study are not done in a chronic way . Shampoo should be safe , not sure about chronic use of lotion or cream .

I've seen a study in which it was not found in blood of patients who used a shampoo for 6+ months. It's mentioned here under pharmacokineticks
https://arpimed.am/1414-2/

Why do you think a shampoo would be safe, but not a lotion or a cream?

 

[jamesbooker1975]

I've seen a study in which it was not found in blood of patients who used a shampoo for 6+ months. It's mentioned here under pharmacokineticks
https://arpimed.am/1414-2/

Why do you think a shampoo would be safe, but not a lotion or a cream?

Cause the time it pass on the scalp. On google, you can find comments of people using cream and check they testosterone level and have a significant drop cause this.
Also, when you use chronic lotions, you skin tend to me much more permeable .

 

[dale2]

Can you point me to studies about its androgen receptor-binding properties?

 

[Dimitri001]

Cause the time it pass on the scalp. On google, you can find comments of people using cream and check they testosterone level and have a significant drop cause this.
Also, when you use chronic lotions, you skin tend to me much more permeable .

Just to make sure I understand what you're saying, you're saying a shampoo would be safe because it gets applied and washed out, whereas a cream you apply and you leave it on?

Do you per chance know of any studies of creams showing a testosterone drop?

Can you point me to studies about its androgen receptor-binding properties?

Sorry, I don't remember where I read that, but it wasn't a study, also.

 

[dale2]

Ok, the reason I asked is that the last time I reviewed the literature I found that the AA properties of kcz were just a hypothesis, another was that its antifungal action had an indirect positive effect on hair growth or against hair loss. Since this whole thread is based on kcz having AA properties, I thought maybe I missed some study or new ones had been published.

 

[Dimitri001]

I looked it up. A study says "Ketoconazole, (Nizoral) shampoo, is also known to inhibit 5AR, the enzyme which converts testosterone to DHT."

So it does have AA properties, but the mechanism is not binding to receptors, at least according to this study, unless it both blocks receptors and inhibits AR, which I doubt.

 

[dale2]

Thanks, I looked up that study (Rafi and Katz 2011) but they take its 5AR inhibiting properties for granted (none of the sources listed supports that statement) so I did some more research and found more secondary sources (including Kelly et al. 2016) which eventually led me to compile a list of primary sources:

Sonino, N. 1986. The endocrine effects of ketoconazole.
Sonino et al. 1990. Low-dose ketoconazole treatment in hirsute women.
Shaw, J. C. 1996. Antiandrogen Therapy in Dermatology.
[Hugo] Perez, B. S. 2004. Ketocazole [sic.] as an adjunct to finasteride in the treatment of androgenetic alopecia in men.
Inui, S., and Itami, S. 2007. Reversal of androgenic alopecia by topical ketoconzole [sic.]: relevance of anti-androgenic activity.

Kind of disheartening that 2 out of 4 authors misspell kcz in the title but never mind. Sadly most of these studies are not freely accessible, so most of my questions are still unanswered. However, my first impression is that the AA properties of kcz are only documented for oral doses several times higher than the therapeutic dose for fungal infections. When Nizoral shampoo was found to be somewhat effective for hair loss, some researchers understandably connected this with said properties but the evidence for such connection is still unconclusive. Kelly et al. summarize the Perez study as "its use in combination with oral finasteride ... might produce an additional decrease in scalp DHT levels" and other authors are similarly cautious about this effect. The hypothesis that it is its antifungal properties that are beneficial for some or all hair loss patients is usually presented with more confidence.

To me this is good news because I have been using Nizoral for about 6 years, although not on a regular basis, and from what I learned today it seems that endocrine effects are highly unlikely at the dose/frequency usually recommended for hair loss. Also, when they did appear they were reported to reverse rather quickly and fully...

 

[Dimitri001]

Thanks, I looked up that study (Rafi and Katz 2011) but they take its 5AR inhibiting properties for granted (none of the sources listed supports that statement) so I did some more research and found more secondary sources (including Kelly et al. 2016) which eventually led me to compile a list of primary sources:

Sonino, N. 1986. The endocrine effects of ketoconazole.
Sonino et al. 1990. Low-dose ketoconazole treatment in hirsute women.
Shaw, J. C. 1996. Antiandrogen Therapy in Dermatology.
[Hugo] Perez, B. S. 2004. Ketocazole [sic.] as an adjunct to finasteride in the treatment of androgenetic alopecia in men.
Inui, S., and Itami, S. 2007. Reversal of androgenic alopecia by topical ketoconzole [sic.]: relevance of anti-androgenic activity.

Kind of disheartening that 2 out of 4 authors misspell kcz in the title but never mind. Sadly most of these studies are not freely accessible, so most of my questions are still unanswered. However, my first impression is that the AA properties of kcz are only documented for oral doses several times higher than the therapeutic dose for fungal infections. When Nizoral shampoo was found to be somewhat effective for hair loss, some researchers understandably connected this with said properties but the evidence for such connection is still unconclusive. Kelly et al. summarize the Perez study as "its use in combination with oral finasteride ... might produce an additional decrease in scalp DHT levels" and other authors are similarly cautious about this effect. The hypothesis that it is its antifungal properties that are beneficial for some or all hair loss patients is usually presented with more confidence.

To me this is good news because I have been using Nizoral for about 6 years, although not on a regular basis, and from what I learned today it seems that endocrine effects are highly unlikely at the dose/frequency usually recommended for hair loss. Also, when they did appear they were reported to reverse rather quickly and fully...

That's interesting, thanks!

You might try punching those articles into google scholar, if you haven't. It will often offer a link to a free version, or, failing that, you might try Library Genessis to get access.

Perhaps there still are AA effects, because the dosage required for such effects might be lower when applied topically, directly on the follicles, then when it is taken orally - this is just rank speculation by me, mind you. I don't know whether that's possible, but I imagine it could be. It does appear, based on the study I referenced, that when applied topically it doesn't get into blood, so, presumably, any AA effects would only be local.

I'm also glad to hear that there aren't any AA effects, because I'm considering using a kz shampoo or even cream, but I don't want to use anything that screws with hormones. You say "when they did appear they were reported to reverse rather quickly", so you have found some studies in which they've found some hormonal effects? Do you have a link per chance?

There may be something to the antifungal theory, because there've been studies which have shown that essential oils, alone or in combination with minoxidil, will give results. I'm not sure whether the mechanism by which this is achieved through EO is known, but most of them have some kind of antimicrobial property, so perhaps that's the mechanism common to EO and kz.

 

[dale2]

My source for the hormonal side effects was mainly Sonino 1986, specifically the first two pages which are freely available on the publisher website.

I wanted to look more into the issue of possible systemic absorption and what topical dosage would be best but haven't found the time yet. Anyway the sources you linked are quite reassuring... After all this is not a drug that primarily targets the endocrine system (as fina) but one that does something else (antifungal) and only at much higher doses happens to affect that system...

 

[Dimitri001]

Let me know what else you find out

 

[dale2]

I haven't done any more research, but I do have a question: if the mechanism of action of kcz is to act as an AA (and somehow affect local DHT levels) how come it is effective as a shampoo? That is, being applied only 5-10 mins and then washed away, every 2-3 days?