Why You Likely Don't Have To Worry About Androgen Receptor Upregulation

Quineapig

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Do you work out, take DIM, or otherwise try to keep your T high and estrogen low?

Yeah, I go to gym twice a week and run/swim twice a week. I dont try to keep my T high. Just want to take care of my body.
Im not a bodybuilder or anythin and I don't use protein shakes, pills etc.
I would like my estrogen to get higher because estrogen is what makes your hair grow.
People think I workout alot and use some stuff because I have athletic body, but oh boy if they knew what drugs im taking... :D:D maybe spironolactone is my secret of success.
What is DIM?
 

countjulian

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Yeah, I go to gym twice a week and run/swim twice a week. I dont try to keep my T high. Just want to take care of my body.
Im not a bodybuilder or anythin and I don't use protein shakes, pills etc.
I would like my estrogen to get higher because estrogen is what makes your hair grow.
People think I workout alot because I have athletic body, but oh boy if they knew what drugs im taking... :D:D maybe spironolactone is my secret of success.
What is DIM?

diindolylmethane, it reduces estrogen and raises T. I am shocked your dick still works and you haven't developed gyno.
 

IdealForehead

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Another way of looking at the concept of androgen receptor upregulation and whether it should be a realistic concern, more directly as it relates to hair, is to simply observe what we see from the best studied anti-androgenic hair loss treatments.

Finasteride has the best studies overall, and works by reducing scalp DHT by around 60%. If androgen-receptor upregulation was a common or expected response to androgen deprivation, we should see hair counts drop off rapidly once this upregulation effect "kicks in". In actual fact, what we've seen in the studies is that hair counts stay very stable over long periods of finasteride use.

060406_propeciachart.jpg


People that respond initially continue to respond long term. People who don't respond initially are either so androgen sensitive the partial DHT reduction is not sufficient to block further damage, or their DHT is not being reduced at all (which was my case).
 

Quineapig

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diindolylmethane, it reduces estrogen and raises T. I am shocked your dick still works and you haven't developed gyno.
I did develop gyno in the beginning but I just got off meds for 2 weeks and started again. I figured out that if Im drinking lots of alcohol when on spironolactone I get gyno. Dick was always hard as rock, never betrayed me.
 

Andrew11

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Finasteride only reduces scalp DHT by around 60-70% (ref).

So you still have 30-40% of your scalp DHT left in tact while on finasteride, plus ALL your testosterone.

Testesterone binds to the androgen receptor 3-5x less strongly than DHT, but it still binds and will damage your hair.

The only practical solution to an indadequate effect on finasteride/dutasteride is then to add a topical (or oral) androgen receptor antagonist which can "clean up" and block the rest of this mess still left behind even after finasteride/dutasteride have done their best work.
Old thread but what do you think of someone who has oily skin acne and high testosterone ? Does this make me more susceptible to accelerating male pattern baldness and therefore less of a candidate for finasteride.
 

Screeech

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I have read many times people suggesting that if they use finasteride/dutasteride/RU/etc. they are concerned their hair will "upregulate androgen receptors" which will thus lead to them overcoming the medication or developing "reflex hypersensitivity".

It is true that androgen deprivation/blockade will likely lead to upregulation of androgen receptors. But the only studies I've seen on it suggest it's a transient and weak process.

How Prostate Androgen Receptors Respond to Castration
As an example, this was an animal study of how castration (both physical - cutting off the nuts, and chemical with the androgen receptor antagonist flutamide, etc.) affected androgen receptor expression in the prostates of rats.

Here was their primary finding on physical castration, which matched what they saw with chemical castration:

View attachment 71294

In other words, there was a temporary increase in androgen receptor expression after the castration, but it went back to normal levels within a week.

Here is what they had to say about it:

View attachment 71295
View attachment 71296

In other words, they suggest both their study and a previous study by "Prins" showed only a temporary small effect of androgen receptor upregulation induced by androgen deprivation.

There is likely no plausible mechanism by which your hair will therefore infinitely or massively increase its number of androgen receptors in response to any degree of anti-androgen treatment, and this is likely nothing to worry about.

It's not perfect evidence to prove the point, but unless someone has something to the contrary, I think it's pretty good.

How Hair Responds to Androgen Deprivation
Another way of looking at the concept of androgen receptor upregulation and whether it should be a realistic concern, more directly as it relates to hair, is to simply observe what we see from the best studied anti-androgenic hair loss treatments.

Finasteride has the best studies overall, and works by reducing scalp DHT by around 60%. If androgen-receptor upregulation was a common or expected response to androgen deprivation, we should see hair counts drop off rapidly once this upregulation effect "kicks in". In actual fact, what we've seen in the studies is that hair counts stay very stable over long periods of finasteride use.

View attachment 71930

People that respond initially continue to respond long term. People who don't respond initially are either so androgen sensitive the partial DHT reduction is not sufficient to block further damage, or their DHT is not being reduced at all (which was my case).

The study on castration/ anti-androgen covered 7 days worth.

That is such a small timeframe that anything that you can take from it is absolutely moot.

And the study on finasteride still shows an increasing decline in hair density; and also most importantly, going off all the anecdotal reports of finasteride ceasing to be effective for users, it is around the 5-10 year period where it completely fails to work, which this study omits as it only covers the first 5 years.

So again, somewhat moot regarding treatments losing efficacy due to acquired tolerance over long-term.
 

washed_up

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The study on castration/ anti-androgen covered 7 days worth.

That is such a small timeframe that anything that you can take from it is absolutely moot.

And the study on finasteride still shows an increasing decline in hair density; and also most importantly, going off all the anecdotal reports of finasteride ceasing to be effective for users, it is around the 5-10 year period where it completely fails to work, which this study omits as it only covers the first 5 years.

So again, somewhat moot regarding treatments losing efficacy due to acquired tolerance over long-term.

There are different studies showing different results though. There's the one famous study that showed improvements after 5 years with the theory being that miniaturization is not an immediate process so reversal wouldn't be either.

Putting aside the difference in results, I think it's fair to say that "reflex hyperandrogenicity" is wayyy overblown on the internet.
 

Feelsbadman.jpg

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Right. I agree with your saying about receptors too. Also hamilton found that older men injected with androgens lose their hair faster then younger men. IMO as you get older sensitivity continues to increase. We dont understand sensitivity to androgens in the first place so its hard to know why this is, but it seems to happen

I think this is relatively easy to explain. 5AR levels increase with age. Aging castrated men don't lose their hair because they have almost no T however 5AR has other purposes in the body (glucocorticoid metabolism) and as you age, it does increase. So when you add T to a middle age castrate compared to a younger one, he will bald faster due to having much more 5AR. It would be interesting if the same experiment was carried out today on castrated men who were on a 5AR inhibitor, both old and young.

I think the pseudohermpahodites prove this. They never recede regardless of age. No increased sensitivity without DHT.

T alone is not androgenic enough to initiate this process. DHT is highly androgenic and is needed to activate highly androgen dependent genes where as T has a 1:1 ratio of being anabolic/androgenic. DHT makes you more androgenic and less anabolic. This is what happens in male aging. T levels fall but DHT levels stay the same or increase due to ever increasing 5AR. This is why men become hairier and balder despite T levels decreasing the older they get. My opinion anyway.
 

bridgeburn

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I think it's fair to say that "reflex hyperandrogenicity" is wayyy overblown on the internet.
tolerance and sensitivity apply to some extent to pretty much everything in life
 

neddy2016

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I am apparently sensitive to any type of anti-androgens. the moment i take anything like finasteride, dutasteride, Palmetto or apply any to my scalp, i then spend at least 2 days with a receding scalp itch. this never used to be the case before i took dutasteride. i dunno what happened but that stuff really left me with nothing.

The only thing that has helped abit with the itch is Nioxin 2 shampoo for some reason... and i fairly certain that stuff dries my hair out and makes me shed... so its not one i can keep using :(

My guess is my immune system did not like the amount of effort i put into stopping my hairloss and has pretty much taken any anti-androgens as a threat to my system now.
 

Karan48281

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I have been a lurker on the forums for a while now. Around 1 year ago i decided to take dustaride in order to deal with my receding hairline and diffuse thinning. It was going well for a week, then i started to get a itchy scalp,oily skin and shedding. I decided to stick with it, however the itchy scalp and oily skin did not go, i also gained more acne. The shedding did not stop either. I have diffused even further. I eventually got off the drug 4 months later. I don't know what is going on but the symptoms to be seem to be reflex hyperandrogenicity. So I think I have it for sure.
 

jazz1

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I have maintained my hair well on Finesteride from
Internal and topical. I also wash my scalp daily using a pre cleanser like dawn dish wash and than I use a regular rotating shampoo like Regenepure DR/Revita/BIG3 and Nizoral in different days but washed daily. I also oil my scalp every night. My hair has maintained very well for years using this method. The dawn dish wash cleanses the scalp and sebum production, to allow the DHT shampoos to work well alongside the topical finesteride lotion I use.

Diet is clean low sugars and i try to exercise regular. I have realised that you must target both internal and topical. Topical finesteride from what I read blocks scalp serum DHT by 90% +.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609098/

Quote this study:

Combining topical finasteride with other agents
Research has also been completed to demonstrate the efficacy of topical FNS for Androgenetic Alopecia in comparison to topical combination therapies. A novel combination topical treatment by the name NuH Hair [topical FNS, dutasteride and minoxidil (MNX)], was formulated by Rafi and Katz (2011). 15 male patients were asked to apply the solution daily for nine months and were given the option of adding three further components to their treatment protocol: 1) oral FNS 1 mg daily 2) topical MNX 5% foam applied at least once per day, and/or 3) topical ketoconazole 2% shampoo applied 2–3 times per week. Eight subjects chose aggressive treatment with all four treatment modalities simultaneously. While all 15 patients demonstrated significant growth of hair by the end of the treatment period, the eight patients who utilized all four treatment options experienced significant growth in as little as 30 days; for the patients using topical FNS/dutasteride/MNX alone, significant hair growth was experienced after three months. The topical FNS/dutasteride/MNX was formulated as a hypoallergenic lotion and found to be safe even in subjects with atopy.14


This is the link for anyone interested in topical 15% minoxidil finesteride lotion that also contains other anti androgen ingredients.

https://www.hairlosstalk.com/intera...eck-here-for-alternative.121814/#post-1797859
 
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