Since I’m new here (and new to PFS in general), I thought I would work back through the first principles of what may be happening to us. I think it might be a good exercise for many of the tenured and jaded here, and it may just prompt some new lines of inquiry for some sufferers.
It seems to me that there are a few disparate pathologies at play here:
There are those who develop PFS rapidly upon a dose or two–this is pure speculation but it seems somewhat reasonable to assume that these folks have a genetic predisposition to be permanently affected by any type of 5AR inhibition. The drug effectively turns off some 5AR activity permanently or quasi-permanently.
There are those that take it for a moderate amount of time, develop symptoms while on the drug, discontinue it and see a potentiation of those same symptoms, possibly due to some over-swinging of the 5AR pendulum or due to some pathologic 5AR damage.
There are those who take the drug without symptoms or with mild symptoms for variable lengths, quit, and develop symptoms. This again could be due to an overcompensation of 5AR activity or an up-regulation of 5AR metabolite receptors with no sensitive feedback loop. (I count myself as part of this group)
And there are those that take it for prodigious amounts of time, and either never quit and can function relatively normally or do quit at an advanced age and experience a complete system shut-down.
Now, there are only a finite number of things that could be wrong with us as a direct result of the drug (not counting second order ramifying effects from our primary symptoms). We know that 5AR catalyzes and modulates these specific reactions:
Cholestenone → 5α-Cholestanone
Progesterone → 5α-Dihydroprogesterone
3α-Dihydroprogesterone → Allopregnanolone
3β-Dihydroprogesterone → Isopregnanolone
Deoxycorticosterone → 5α-Dihydrodeoxycorticosterone
Corticosterone → 5α-Dihydrocorticosterone
Cortisol → 5α-Dihydrocortisol
Aldosterone → 5α-Dihydroaldosterone
Androstenedione → 5α-Androstanedione
Testosterone → 5α-Dihydrotestosterone
Nandrolone → 5α-Dihydronandrolone
So there’s only a handful or permutations of disordered 5AR substrate and metabolite concentrations that could explain our first-order symptoms. Namely, we ought to test all of the first column endogenous hormone levels in our body, and all of the second column metabolites (or any other compound that is able to portend by proxy these concentrations).
I’m sure previous users have gone this route, but I’m curious whether they have (a.) done extensive enough testing in this space and (b.) if anyone has utilized an endocrinologist to impute 5AR efficiency and output scores from the ratio of these chemicals.
Two confounding variables that I believe make PFS especially tricky are that (1.) an upregulation of tissue-specific receptors for these metabolites occurs as an intuitive physiological response to their underproduction while we were on Finasteride. This doesn’t appear easily reversed and may indicate that these tissues are receiving too much of the intended signaling molecule. Relatedly, (2.) many of the second-column metabolites are biphasic in nature, so that an over or an underproduction of that specific chemical can cause the same symptoms. To instantiate that point, some PFS sufferers have the same mental symptoms as me (brain fog, altered consciousness, vision acuity issues, and head pressure), yet they only took one dose. I, on the other hand, took it for 3.5 months without symptoms and developed them only upon cessation. I may be experience an over-production of allopregnanolone, for example, (or normalized production but higher tissue sensitivity from more receptor density) while the one-dose crowd may be experiencing an under-production of the same molecule. Its biphasic nature effectively renders us the same symptoms.
The varied constellation of symptoms could be due both to genetic propensity towards tolerance in varying tissues and also to pre-fin hormone levels. I’m very curious about those specific enzyme-catalyzed reactions above and how my intra-cranial levels of the cortisol and progesterone-based metabolites look. I’m very convinced that my isopregnanolone (which can influence saccadic eye movements) levels are quite sideways. In the coming few weeks, I have appointments to see an endocrinologist, neurologist, and ophthalmologist. And I’ve done preliminary bloodwork with with my Internal Medicine Physician and evinced normal blood levels of testosterone, cholesterol, and thyroid hormone.
If anyone has had any previous success with this route of inquiry, please let me know and please add any thoughts you might have. I’m lucky in that cost is not much a concern for me so I’m going to pursue as many tests as possible and hopefully shed some light of what some of the underlying pathology may be.