How Accutane can cause similar effects if it is not an 5AR inhibitor?

isotretinoin
accutane
#21

Very likely @acne1776 - epigenetic changes are site specific. I would expect the results from the coming tissue analysis to be quite different.

The skin in the bwh study was taken from the upper back (I believe in a departure from agreed protocol) and the appendices of the study (accessed separately from the main paper for some reason) suggests there was differences in “a few” androgen dependent genes. It did not specify which. They dismissed this because their correlation method did not pick up on a consistent pattern. The fact this was glossed over in a couple of undetailed sentences was disappointing, as with most aspects of this costly waste of time.

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#22

That is of course correct. But given that:

  • finasteride is primarily an inhibitor of 5ar2
  • 5ar2 is strongly expressed in the genital region (prostate, penis)
  • a clear effect in the form of a deregulated AR has already been found in penile tissue
  • erectile dysfunction is a commonly observed persistent adverse reaction with PFS patients
  • back region has been documented to not be particularly rich in 5ar2

What was the motivation of Bhasin to choose back skin which afaik has not been documented to express high levels of 5ar2 in adults instead of previously validated penile tissue? Why was origin of skin not mentioned anywhere in the main paper (only in a separate appendix)? Why was it not disclosed specifically which androgen-dependent genes were investigated? In the appendix, it was mentioned that “a few” androgen-dependent deregulated genes had been found, but not which ones. Why was this not mentioned in the main paper?

For me, this paper was carefully designed to show that the PFS patients are simply depressed, and to distract from any cell level damage as has been previously found. The only reason I see for such a top notch scientist to produce such a lousy paper, and given the substantial budget he had, is sabotage. Anyhow, I will arrest my case now. This topic is about Accutane.

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What I believe PFS is
#23

Something that is overlooked.

Accutane has been shown to be a very potent competitive inhibitor of RoDH4 at therapeutic concentrations of the drug and RoDH4 has been identified as one of the “molecular switches” that governs ligand access to the androgen receptor through conversion of A-diol to DHT, a so called “back door” pathway. There is a nice description of the blocking of these oxidative HSDs as a potential acne treatment in this patent application. Unfortunately, data regarding whether Accutane does or doesn’t competitively inhibit any of the oxidative 3a-HSDs except for RoDH4 appears to be absent.

This back door oxidative pathway may be crucial to maintaining DHT levels by countering reduction of DHT to A-diol.

The direct enzyme inhibition could explain the “early” anti-acne effects (and side effects) of Accutane that are observable after only 1 week and before mRNA levels of steroidogenic enzymes (such as 5ar-I, 3b-HSD, and DHSR9 (an oxidative 3a-HSD)) are significantly decreased, as they are after 8 weeks of treatment.

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A possible Hormetic/Biphasic effect of Accutane on neurosteroid production
#24

Dubya! Maybe this explains my condition. After taking the second pill of Accutane, i remember my low back hurting that morning. My lips were dry and my facial skin started to fall apart. This all went away except sexual sides. Do you have any idea why this happened to me? Maybe my prostate was prone to kind of a disease from the beginning of my life… How the hell i get this from 4 pills total. My DHT should have healed itself if it was the real problem.

#25

I think the sharp reduction in DHT causes this problem. It doesn’t matter if DHT production returns. Putting out a fire doesn’t fix a burnt-down house.

#26

Dont think so, because a lot ofmpeople feels better afternquitting, during 2,3,4 weeks, and then crashed.
Somis not dht reduction.

Regards.

#28

Have you ever tried DHT or test?

#29

No, not yet. But i did try creatine and some other supplements, no significant improvement has been seen. Did you use it?