PROPECIAHELP: Persistent Finasteride Propecia Proscar side effects info & discussion forum

Having been on TRT before taking fin, I know what even small doses of TRT normally feels like: Good. Now, no matter what I take, I feel nothing positive - actually high doses of androgens make my symptoms WORSE. I've also messed with reducing estrogens via Arimidex and even Aromasin. Nada.

For those that have been there, the conclusion is clear: Androgen insensitivity is the only answer. There is no way on this frickin planet that any hormonal "excuses" can even come close to explaining this. If you think about it, what has happened becomes very clear:

5AR inhibitor massively reduces cellular and circulating DHT levels
AR becomes hypersensitive (google terms androgen receptor hypersensitivity) due to low androgens. This is why we get hypogonadal LH/T values.
Side effects start
We quit 5AR inhibitor
DHT returns full force and hits upon hypersensitive AR (do the math 100% > 30% is a 70% reduction. 30% to 100% is a 333% increase. Combine this with a hypersensitive AR and you get a train crash. This is why the symptoms really go south about 1-2 weeks after quitting.
AR negative autoregulation kicks in an probably methylates some AR regulatory element, effectively silencing the AR signlal

The approach we have to take to this is to understand what changed and try to undo it. Overloading the system with further hormones will not work in many cases. Some guys do indeed seem to be lucky enough to have enough remaining sensitivity to get some benefit from hormones. Most of us, however will not - or even get worse by using them.

Btw, common misconception on this board: Adiol-G is about 75% a marker of AR gene expression and NOT of 5AR activity. 3a-HSD is mainly induced by AR gene expression. The remaining 25% come from direct induction by androgens (likely) or some other hormone (maybe). That is why you can have perfectly good serum DHT values and still have fucked up Adiol-G, because low Adiol-G is mostly telling us something about Androgen sensitivity.

There currently is no proof that 5AR2 deficiency has anything to do with these side effects. If the problem were that simple, supplementing DHT (i.e. Andractim) would alleviate the problem in every case, which unfortunately isn’t true.

Even though a few men seem to benefit from supplementing DHT, many have made the experience that increasing androgens by any means (Clomid, TRT, DHT, etc.) makes the symptoms worse.

This clearly indicates that the problem is more complex than simple 5AR2 deficiency and more akin to an active resistance of the body against androgens. Misguided androgen receptor autoregulation mechanisms, which silence the AR signal, is a more likely possibility which must be considered.

3a-Androstanediol Glucuronide (3a-diol-G) is a metabolite of the enzyme 3a-HSD, which is responsible for maintaining androgen homeostasis at the cellular level. Given that 3a-HSD is probably induced by AR gene expression, a lack thereof, due to silencing of the AR signal, would equally lead to low 3a-HSD throughput. This would also result in low 3a-diol-G levels. 3a-HSD additionally plays a central role in the synthesis of key neurosteroids. Hence a downregulation of this important enzyme would better explain “brain fog” and depression rather than low progesterone levels would, which many patients don’t even have.

So let’s stick with the facts and not start potentially damaging treatments based on misleading information. The only way we are going to progress in this issue is by getting science involved and not by making wild claims in the Internet."

Will start this tomorrow.

Awor is telling me injections probably will not work

Shippen said "a doctor in Europe" was having success with procaine.

Procaine by a delivery method other than IV will not work for our purpose. The reason for this is the extremely short half life of only about 40-80 seconds.

As to why some people get better on their own: That's a good question. For one, enzymes exist which demethylate. JHDM2A for example, demethylates promoter regions of genes which express AR regulatory elements. Secondly, it is also possible to loose small amounts of methylation during a cell replication cycles if enzymes responsible for methylation are not sufficiently active (DNMT1, DNMT2 for example). To be frank, the exact function of epigenetic processes such as methylation is still relatively poorly understood. There is still much that needs to be discovered.