Nice observation! Happy that our science guy noticed this about Melcagni’s 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 “shutting down” 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 
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, “Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action,” Dermato-Endocrinology , vol. 1, no. 3, pp. 177–187, May 2009.
Full PDF link:
http://www.tandfonline.com/doi/pdf/10.4161/derm.1.3.8258?needAccess=true
…A 6-fold decrease in HSD3B1
I’m not sure. Retinoic acid stimulated neurosteroidogenesis in glial cells and induction of HSD3B was noted, along with p450scc and StAR:
This would be excellent. I’m still somewhat skeptical that it would happen but hey, who knows.
I can’t 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 don’t know how patent laws work outside of the USA.
8 posts were split to a new topic: Discussion of 5-ar II gene methylation as an effect of AR overexpression
I’m REALLY sorry to interrupt, but seeing as lots of the clever people are all together here I thought I’d 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.
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 17β-HSD.
Incidentally, scientific research has shown that SSRI class medications such as fluoxetine and paroxetine induce a 63 to 163 fold upregulation of 3α-HSD and 17β-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 3α-HSD/17β-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.
Because of over expression lowering androgenic activity has helped some.
Vitamin A supplementation increases levels of retinoic acid compounds, but Vitamin A it is also a 5ari.
All carotenoid are 5ari, for example Astaxanthin.
Straight up DHT isn’t the answer to our cure. Transdermal testosterone heavily transforms into DHT. And DHT derivative steroids exist that don’t bring us a cure.
I personally believe there may not be a cure you take once and you’re 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.
I also bro…
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
That’s not entirely true.
“…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.” - 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. I’m 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. I’m not disagreeing with you there.
This is amazing information thanks for sharing
This study reveals valuable information about mental and physical problems in PFS patients. If someone has problems with SRD5A2 then they have trouble creating the steroids that give us energy, confidence, focus, vitality, libido etc etc etc. Here is more on SRD5A2:
Reference: https://ghr.nlm.nih.gov/gene/SRD5A2
“The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to a more potent androgen, dihydrotestosterone (DHT), in male reproductive tissues.”
Although must of us suspected this, it is good to have science to back it up.
If what you said is true, it is very easy and very fast to check SRD5A2 status with all DNA and RNA testing technology that exist today.
What it is even more shameful is that RC Melcangi in Italy had done 2 studies and already published and Baylor study the first part is not even have been published yet
(emphasis mine)
As far as I understand it, almost half of PFS patients did not have methylated SRD5A2 promoters. If that half also has horrible side effects, the mechanism behind PFS has to start somewhere else and the SRD5A2 might be a downstream effect for some. If 95% had an abnormality versus control and it explained physical symptoms we are onto the juicy stuff :).
If what I am saying is false, correct me. Just how I as a regular sufferer with no scientific background read the above summary.