New idea about finasteride-induced HPTA shutdown

General Discussion
#1

First of all, note the distributions of type 1 and 2 5AR…

blackwell-synergy.com/doi/ab … 06.00053.x

“In humans, Type I 5á-reductase is found primarily in the sebaceous glands of most regions of skin including scalp, and in liver, muscle, and brain (31,140), with low levels also present in prostate that may increase in prostate cancer (142).”

“The Type II 5á-reductase isozyme is found in prostate, seminal vesicle, epididymis, and hair follicles as well as in liver (140)…”

This tissue specificity may have some important implications.

First consider tissues expressing type 2 5AR. How will the local hormonal milieu be altered? Well, obviously, as we know quite well by now, T increases, DHT decreases, and E increases.

Now consider tissues expressing type 1 5AR. Since they are relatively unaffected by finasteride, they continue to convert T to DHT. With serum T increased, we can now imagine that, locally, type 1 tissues will experience an increase in DHT as well as T. Assuming that DHT acts, in the brain, simply as a more potent form of T (it has 10 times the affinity for the androgen receptor), we can predict that a significant (local) increase in negative feedback should occur. This, obviously, is bolstered by the increase in serum E, as well as the increase in local aromatase enzyme activity (again due to the increase in serum T).

Note also that this theory implies that HPTA shutdown should be more common in finasteride-users than dutasteride-users.

#2

Interesting theory… perhaps one day a research study will be conducted to monitor what exactly changes in some men after discontinuing Finasteride, to see what the fundamental issues are that caused some of us to crash. However, I’m not holding my breath.

Regardless, would be interesting to test your theory about Fin users being shut down moreso than Dutasteride users, as this would help serve to “bolster” your point that perhaps it is Finasteride’s selective inhibition of 5ARII that caused us these problems in the end. The question still remains, however, how to correct these issues post-use.

I have read a few anecdotal reports of guys taking a long time to recover after Dut (likely owing to that drug’s long halflife of several weeks/months)… however, the ratio of such stories pales in comparison to Fin ones.

Perhaps the lack of stories is because there are simply not as many people using Dut… or perhaps because as you hypothesize, Dut may not cause such severe issues due to its dual inhibition mechanisms – despite blocking up to 90% of DHT.

PS: I tried hunting down another of your recent posts to me about 5AR upregulation causing negative feedback, but can’t seem to find it? Maybe I’m blind…

#3

Haha…no, not blind…

I felt awkward about recommending to NoMan that he order from an internet pharmacy…I really don’t want to be responsible for guiding someone in the wrong direction. Although, if it were me, I might seriously consider it. If I have to increase T as soon as I possibly can (or so I think), it might make a lot of sense to overnight (if this is possible) a SERM, which would be a lot more effective that herbs in achieving the necessary T surge. But then again, what do I know?

Anyways, also in that post I speculated that the long-term suppression may have upregulated 5AR synthesis. This would make sense, as many biomolecules seem to have self-regulating feedback mechanisms (if the amount goes up, it should act to decrease regulation, and via versa). With finasteride wiping the body clean of 5AR type II, we should then expect basal 5AR production to be maximized. When the drug is ceased, we might then see 5AR resurgence in overdrive, and we might expect to see 5AR production go well beyond it’s typical equilibrium concentration, before the negative feedback kicks in to downregulate its production. In the meantime, DHT would also surge, and this might lead to an effect analogous to HTPA shutdown, induced by acute negative feedback.

I figure this type of mechanism could account for cases like NoMan’s. In his case, we saw problems arise only after 5 weeks off the drug, which is especially interesting as it takes about 30 days for 5AR to return to normal (though in a mouse, if I remember correctly…). Maybe the extra week was 5AR continuing to surge?

I don’t know…just something to think about.