You guys should make it impossible to see posts on the forum, until users sign up, login, and take the survey. Even for lurkers.
Just until the goals are met.
Just my opinion
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This is actually another shortcoming in RMās paper: He is focusing too heavily on 5ar2, whereby his previous work has shown neurosteroids to be deregulated which have nothing to do with 5ar2 (red/green areas show all down/upregulated NS found). The problem must additionally also be at either the 3b-HSD or even at the P450scc system level, specifically CYP11A1. Unfortunately there was no assessment of Chol substrate levels either.
This unfortunately leaves the impression of more shoe-horning on me (like with the symptom profile), which is really a shame, because basically it would otherwise be good work.
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But how do you know PFS guys have high methylation of 5ar type 2 gene if you only tested 16?
Statistical inference is used in science to extend observations based on samples to larger populations, itās impossible to study the whole worldās population for every condition. So there is a nees to produce samples to estimate larger populations. This is how science work, without knowing statistics it is impossible to fully understand the results.
Nice observation! Happy that our science guy noticed this about Melcagniās studies too.
Would like to mention that HSD3B was one of the most profoundly down-regulated genes in a study of the effect of Accutane on skin cells. Just a hunch that it is indicative of a cell āshutting downā all steroidogenic machinery.
Could you link that study please? Sounds interesting, though things often work differently in the brain than in other sites. Nevertheless, might be something worth replicating with finasteride and AD patients. Certainly easier to do with skin than brain cells, though we would need to pick 5ar2 rich cell lines for finasteride users, unlike what Bhasin (BWH/Harward) did 
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Suspect you have read this one before. It also shows a decrease in transcription of 5-ar type I and a 3a-HSD enzyme (DHRS9)
A. M. Nelson, W. Zhao, K. L. Gilliland, A. L. Zaenglein, W. Liu, and D. M. Thiboutot, āTemporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action,ā Dermato-Endocrinology , vol. 1, no. 3, pp. 177ā187, May 2009.
Full PDF link:
http://www.tandfonline.com/doi/pdf/10.4161/derm.1.3.8258?needAccess=true
ā¦A 6-fold decrease in HSD3B1
Iām not sure. Retinoic acid stimulated neurosteroidogenesis in glial cells and induction of HSD3B was noted, along with p450scc and StAR:
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This would be excellent. Iām still somewhat skeptical that it would happen but hey, who knows.
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I canāt answer that for you. Maybe the company would put out a European product on the market in the future. Or, another company produces an allopreg medication, but I donāt know how patent laws work outside of the USA.
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8 posts were split to a new topic: Discussion of 5-ar II gene methylation as an effect of AR overexpression
Iām REALLY sorry to interrupt, but seeing as lots of the clever people are all together here I thought Iād ask:
The ONLY mechanism by which DHT is made, is where 5AR converts Testosterone into DHT - is that right?
Thanks all, sorry to butt in.
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Yes and No. 3a-HSD regulates the amount of DHT available at the receptor (AR) level by converting DHT to Androstenadiol and back. Androstenadiol is a practically inactive androgen. But for that to happen, you need DHT in the first place, which is through conversion of T to DHT via 5ar. Testosterone can be deactivated through 17Ī²-HSD.
Incidentally, scientific research has shown that SSRI class medications such as fluoxetine and paroxetine induce a 63 to 163 fold upregulation of 3Ī±-HSD and 17Ī²-HSDactivity (Griffin LD, 1999) . The upregulation of these androgen reducing enzymes will lead to a significant reduction in DHT at the cellular level. As such, from the point of view of the androgen receptor, the inhibition of 5AR and upgregulation of 3Ī±-HSD/17Ī²-HSD activity have exactly the same effect, namely to reduce the amount of androgens available at the androgen receptor level.
Even though this effect has not yet been investigated outside of the brain, it appears plausible that this is a mechanism which can contribute to causing the same persistent side effects as other androgen depleting substances, given the common persistent side effect profile.
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Because of over expression lowering androgenic activity has helped some.
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Vitamin A supplementation increases levels of retinoic acid compounds, but Vitamin A it is also a 5ari.
All carotenoid are 5ari, for example Astaxanthin.
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Straight up DHT isnāt the answer to our cure. Transdermal testosterone heavily transforms into DHT. And DHT derivative steroids exist that donāt bring us a cure.
I personally believe there may not be a cure you take once and youāre cured forever, but a treatment that you take daily to replace what is lost in the body.
I have most of the worst physical symptoms of PFS, as well as the worst neurological and sexual symptoms of PSSD. And I only took ADs.
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I also broā¦
in my point of view that doesnt make sense. what is lost in the body ? something is not working correctly or is silenced. nothing is lost. we dont have a lack of hormones
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Thatās not entirely true.
āā¦decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients. Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF. Finally, finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.ā - Melcangi 2017
Lowered progesterone, preg, and dihydroprogesterone are found in our CSF. He goes on to say that those further metabolites and precursors (like allopreg) are also effected. Iām not saying that this is the sole cause of PFS, but simply that it was found that these chemicals are low in concentration in our CSF.
But yes, you may be right that something is silenced or malfunctioning in addition to the low neurosteroids in our bodies. Iām not disagreeing with you there.
This is amazing information thanks for sharing
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