Liver CYP3A4 enzymes and finasteride-induced low T

General Discussion
#1

Finasteride is metabolized by CYP 3A4 enzymes in the liver.

These same enzymes are also responsible for the metabolism of testosterone.

Is is possible that by consuming finasteride daily for an extended period, many of us may actually upregulated the expression of these enzymes?

Then, when we abruptly stopped finasteride, we were left with upregulated CYP 3A4 enzymes, that would have in turn increased their degradation of other substrates, i.e. testosterone.

Could overactive CYP3A4 enzymes be responsible for post-fin low T?

This is just wild speculation I know (don’t take this too seriously)…

I tried to find something (anything) to corrobrate this possibility. I found only this (so far):

surmeno.blogspot.com/2006/03/est … tions.html

“In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John’s Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects… Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.”

This, in effect, demonstrates that altering CYP3A4 enzymes, can in fact lead to changes in overall hormone balance (though in this case for estrogen).

In any case, as wacky as this theory may sound, it would be very simple to test: Just drink grapefruit juice, regularly, to inhibit CYP3A4, and see if any difference is noticed.

Just thinking…

1 Like
#2

Further support for this theory:

freepatentsonline.com/20050176692.html

This invention involves testosterone replacement with an added agent, referred to as “formula 1”, that is claimed to increase the bioavailability of the testosterone.

The mechanism of action of “formula 1” is speculated as occurring as follows:

“The mechanism(s) by which this suprising effect of the compounds of formula I is(are) achieved is uncertain. As hepatic metabolism is thought to be the principle barrier to the absorption of testosterone from the GI tract, it is likely that the effects of these modulatory agents are mostly mediated by inhibition of the hepatic metabolism of testosterone, but not necessarily inhibition of the 5-.alpha.-reductase activity, but possibly via inhibition of androgen metabolism by cytochrome P450(CYP3A4).”

So, inhibit CYP3A4 enzymes, and you increase testosterone.

As finasteride was metabolized by these very enzymes, they might serve as a logical focal point to an effort at side effect reversal.

#3

Your first post states:

Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects

The 2nd post states:

inhibition of androgen metabolism by cytochrome P450

You state: “inhibit CYP3A4 enzymes, and you increase testosterone.”

– Are you sure that is correct based on what they wrote? To me it sounds like if you inhibit CYP3A4, you inhibit T (based on the literature of your 2nd post). So basically, inhibiting CYP3A4 inhibits both Estrogen AND Testosterone…? Maybe I’m reading or comprehending this wrong.

Either way, as I’ve stated in a previous post on this subject ("Liver Stories from Askdocweb), the only time I noticed recovery after my initial 1 week recovery 2 weeks after quitting, was 1 year after when I had Norwalk and was puking bile for a day… I agree, I believe somehow the liver is also implicated in our problems, likely via C19/C21 metabolism pathways and P450 enzymes such as CYP3A4.

#4

As I understand it (at the wikipedia level: en.wikipedia.org/wiki/CYP3A4), CYP3A4 enzymes are responsible for the degradation of both estrogen and testosterone.

The first post refers to inhibition of the enzymes causing an increase estrodiol. This obviously makes sense.

My second reference, I believe, is talking about how orally administered testosterone is made more available because “formula 1” increases bioavailability “via inhibition of androgen metabolism by cytochrome P450(CYP3A4).”

Yeah, so I think I interpret it as: “if you inhibit CYP3A4, you inhibit testosterone (as well as estradiol, I suppose) metabolism, and thus you increase androgen availability.”

…So testosterone would increase, just as estrogen was reported to increase in the estrogen replacement example.

I can’t try this, as grapefruit juice is contraindicated for tamoxifen. But I’d be interested to hear whether anyone in the post-fin low-T situation might notice any effect.

#5

‘jaydee’, a member of the Anabolic Minds forum, provides some insight into liver issues here…

anabolicminds.com/forum/male-ant … zymes.html

Mew: Since you have some reason to suspect that the liver is at fault, at least in your own case, you may want to consider having liver function looked at using a Functional Liver Detoxification Profile.

Just a thought.

#6

Actually my grandfather on my dad’s side died because of liver problems from long-term alcohol consumption. I can definitely see this as a possibility.

#7

Has anyone had a chance to check for liver related problems such as cirrhosis? All of the symptoms we have post-fin could be cirrhosis related, as liver function has a lot to do with hormones. I’m just concerned that scarring of liver tissue is pretty permanent.

I’d be very keen to hear of someone who may have had a biopsy or a complete liver functional liver detoxification profile done.

:confused:

#8

Timebot,

I think your line of thought makes sense, the liver could very well play an important role in triggering our problems while on propecia. On the other hand, i do not think we still have a liver problem. The liver is the organ most capable of regeneration. If it is not metabolizing androgens the way it did before, i believe it is because the liver is not receiving the signals from the proper hormones/enzimes to do it.