Local(scalp) 5ar Inhibition Vs Whole Body 5ar Inhibition

[vlados]

Hi guys

I know I'm a new member here, but I've been lurking for a while here. One matter of interest is about 5 alpha reductates inhibition.

I've seen a couple of users with hair loss but with apparently normal or even lowish levels of DHT. I've also read on this forum that local 5ar (in the scalp ) tends to be more important than whole body 5ar. We all know fina/duta blocks 5ar in the whole body ,lowering both scalp dht and serum dht levels, but by also lowering whole body dht, it can have a myriad of negative effects. I know that with the above I'm only repeating what most ppl here know, but bear with me.

I've came across a study(actually 2) which were more into the dht effects on prostate Patients were given DHT gel. As expected, it lowered their test/estrogen levels but it raised dht levels a couple fold. Even so, the intraprostatic DHT remained very similar between the placebo group and the dht group. So exogenous dht doesn't really affect the intraprostatic DHT levels,it seems, meaning exogenous dht may have a neutral effect on prostate. An authors thought was also that exogenous test may be more troublesome than exogenous dht, because exogenous test tend to increase intraprostatic dht (being converted by local 5ar).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048323/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048323/

Rewinding to 5ar inhibition effects of finasteride, I've also noticed in some studies that 5ari lowers intraprostatic dht quite much and increases intraprostatic test, decreasing the prostate in size (sought for effect).

I know the above was saying more about prostate than hair, but those 2 share similarities, so here's my half assed theory : could you minimize the hair loss by locally inhibiting scalp/hair follicle dht by taking an 5ar inhibitor ,all the same while taking exogenous dht to ameliorate the negative effects 5ar inhibition has like lowered libido,etc ?

I know the above theory may have major flaws so please be gentle

 

[Btg]

Prostate dht is regulated , i reremember a study where they massively dropped test and dht in the prostate still remained in the same levels ( but serum dht took a hit )
With 5ar inhibitors the body cant have normal dht levels so i guess if u apply gel to the prostate it could possibly be used up
The thing is that it is uncertain if sides are associated solely to the dht drop

 

[Tommybommy1363]

I would guess no. There is a lot of evidence that dht is mainly an autocrine/paracrine substance and not and endocrine which would mean serum dht doesn’t likely make much difference.

 

[vlados]

Ok guys, so what do you think would happen in the following scenario :
- To ensure 5ar is knocked out almost entirely, one could take duta (standard dose)
- At the same time ,take DHT (as gel or injections) - this would mean even lower testosterone (from HPTA inhibition)

1) Would you lose hair ? Why?
2) Would the side effects from lowered DHT (like low libido,mental fog,etc) be resolved by having enough DHT in the serum ?

 

[vlados]

Anybody ?

 

[mojojuju224]

I've seen in multiple studies that suggest part of what makes finasteride so effective is its effects on both local (follicular) and serum DHT levels. So, if a certain portion of the DHT found in the scalp is derived from serum (as the scalp is so highly vascular in nature), it stands to reason that a topical solution would not be as effective as a systematic solution, which is part of the reason I'm personally skeptical of topical finasteride. It seems its efficacy would be unlikely to match the efficacy of an oral medication unless it went systematic, but I suppose it's possible if, say, the topical reduced the follicular dht locally to a greater degree with less systematic absorption, perhaps the results could be similar, although it's unlikely if serum does play a part unless the topical had a very long half life. Just my 2 cents, though.

 

[vlados]

Hey mojojuju224,
Do you have any reference that suggest inhibiting serum DHT is also important ? I would be curious to see that.

For example in the following excerpt from a study it is stated that local conversion of t to dht tend to be the most important factor in Androgenetic Alopecia.

 

[mojojuju224]

vlados Yes, this is from Drake L. 1999

"...it seems likely that a significant amount of DHT found in scalp skin is derived from both local DHT production and circulating DHT Consequently, the effect of finasteride on scalp DHT is likely because of its effect on both local follicular DHT levels as well as serum DHT levels."

and from Dallob Al. 1994

"The DHT concentration in full thickness scalp samples may be dependent in part on circulating levels of DHT, because scalp skin is highly vascularized. Finasteride may exert part of its effect on scalp levels by lowering serum DHT." (There are a few other studies I can't particularly remember at the moment, but I'll add them later if I find them).

As for those citations you posted, I don't see how that runs counter to the argument I'm proposing. It's known that circulating androgen levels, e.g. testosterone or DHT, aren't necessarily higher in people with Androgenetic Alopecia, but that doesn't mean those affected by Androgenetic Alopecia aren't sensitive to circulating androgens. Type 1 5a-R is the predominant isozyme in the scalp, but finasteride is selective for type 2, which is found in the dermal papilla; since DHT is a mainly paracrine hormone, local DHT inhibition will always be the preferential target, but it's certainly more than possible and likely that serum levels has an effect over time, albeit small, although it is excreted from serum fairly rapidly. I'm interested to see the most recent results from Polichem, though. Perhaps that will provide some more answers.

 

[vlados]

mojojuju224,

Thanks for providing that info.

2 points :
1)I think we can agree that on the balding areas, there's more local DHT found, so if serum DHT would be important wouldn't the same serum DHT reach all the areas equally(both balding and non balding) ? But as mentioned earlier this doesn't seem the case.

2) It seems that in the balding areas, blood flow is lower than in the non-balding areas, meaning that those non-balding areas(higher blood flow) ironically would "take in" more DHT from the serum/blood, than those balding(low blood flow) areas,but again this doesn't seem the case.

What's your take on this ?