Does nandrolone activate progesterone receptors?

[Gman86]

I’ve heard and read that nandrolone acts on the progesterone receptor. I’m wondering if this activation replaces taking exogenous progesterone at all, even if nandrolone won’t increase progesterone in the serum.

 

[JimGainz]

Normal therapeutic nandrolone doses will not increase progesterone - or only by a point or two if anything. Personally I would cut back on progesterone a bit and add it back slowly after being on nandrolone to be on the safe side (I am overly cautious) but I would expect zero interaction.

 

[Wilson7]

Go to Figure 1 in the paper attached. Gives a laundry list of compounds and their interaction with various hormonal receptors. Yes nandrolone dose activate the PR.

 

[Cataceous]

Normal therapeutic nandrolone doses will not increase progesterone - or only by a point or two if anything. Personally I would cut back on progesterone a bit and add it back slowly after being on nandrolone to be on the safe side (I am overly cautious) but I would expect zero interaction.

By what mechanism would nandrolone increase progesterone at any dose? Or are you just referring to progestogenic activity and not actual progesterone? Isn't nandrolone likely to be suppressive of endogenous production? Is the effect of nandrolone at progesterone receptors additive with respect to progesterone, except attenuated to 22% because of its lower affinity?

 

[DixieWrecked]

By what mechanism would nandrolone increase progesterone at any dose? Or are you just referring to progestogenic activity and not actual progesterone? Isn't nandrolone likely to be suppressive of endogenous production? Is the effect of nandrolone at progesterone receptors additive with respect to progesterone, except attenuated to 22% because of its lower affinity?

This is exactly what occurs. In hindsight this is exactly what I felt on it, estrogen dominance despite nandrolone not increasing estrogen significantly.

It seems it would make sense to supplement with either pregnenolone or progesterone when on Nandrolone.

 

[Cataceous]

This is exactly what occurs. In hindsight this is exactly what I felt on it, estrogen dominance despite nandrolone not increasing estrogen significantly.

It seems it would make sense to supplement with either pregnenolone or progesterone when on Nandrolone.

That's confusing. I thought the point of nandrolone was to reduce estrogenic and androgenic effects. Progesterone itself has some aromatase-inhibiting activity, and it also downregulates estrogen receptors. It seems plausible that nandrolone does the latter when it activates progesterone receptors.

 

[DixieWrecked]

That's confusing. I thought the point of nandrolone was to reduce estrogenic and androgenic effects. Progesterone itself has some aromatase-inhibiting activity, and it also downregulates estrogen receptors. It seems plausible that nandrolone does the latter when it activates progesterone receptors.

Nandrolone was an add-on to my TRT protocol. So I'm speculating that if my progesterone was low, even if my e2 was only slightly above range, I was feeling estrogen dominance.

 

[benaoao]

That's confusing. I thought the point of nandrolone was to reduce estrogenic and androgenic effects. Progesterone itself has some aromatase-inhibiting activity, and it also downregulates estrogen receptors. It seems plausible that nandrolone does the latter when it activates progesterone receptors.

It’s likely that you get the effect that you get from partial agonists ie. opposite of full agonists. Meaning that such a weak binding of the progesterone receptor will actually favor estrogen dominance. My theory is that way less E2 is needed for proper function on Deca. This one dude who reached out to Dr. O’Connor with E2 in the single digits for years feeling perfectly fine on Deca+EQ comes to mind.

People go by the numbers but it’s an entirely different chemical situation vs physiological testosterone, progesterone, etc.

I would supplement pregnenolone tho. But I’d always supplement it when shutting down the HPTA since LH is important for metabolism of cholesterol into preg. Then the body decides what to do with that supplemental pregnenolone based on its own needs. I’d leave it alone with that instead of trying to bring downstream hormones to arbitrary numbers based on science established in natural adult males.

 

[Cataceous]

...
I would supplement pregnenolone tho. But I’d always supplement it when shutting down the HPTA since LH is important for metabolism of cholesterol into preg. Then the body decides what to do with that supplemental pregnenolone based on its own needs. I’d leave it alone with that instead of trying to bring downstream hormones to arbitrary numbers based on science established in natural adult males.

But it's also possible that HPTA suppression leaves the body without proper feedback about "its own needs." If this is the case and some downstream hormone levels are relatively low then it may well be better to target healthy average levels. It's also guesswork as to how much pregnenolone to take and in what form. Oral administration probably yields very different and less natural results than a parenteral route.

 

[benaoao]

Sure thing but healthy based on what? If you’re on a nandrolone base then cellular ratios are completely different so serum levels mean… not much?

Deca base 300/wk
EQ is in and out
GH is in there as well.

Lab review 4min20sec in. E2 sensitive is 6.0, reports feeling great. It’s anecdotal but it’s in line with studies on nandrolone only where they don’t bother tweaking anything and quality of life seems fine.

 

[Gman86]

That's confusing. I thought the point of nandrolone was to reduce estrogenic and androgenic effects. Progesterone itself has some aromatase-inhibiting activity, and it also downregulates estrogen receptors. It seems plausible that nandrolone does the latter when it activates progesterone receptors.

Was just listening to a podcast this morning where the guy from Ray peats forum, Haidu, was mentioning how progesterone has some aromatase inhibiting properties, as well as downregulates estrogen receptors, just like u said. He also said vitamin E does these two exact things as well. Have u ever heard or read about vitamin E inhibiting aromatase and downregulating estrogen receptors?

 

[benaoao]

It’s a partial agonist, so it replaces progesterone while exerting a weaker effect. So that triggers estrogen dominance. Read up on partial agonists.

 

[Cataceous]

Sure thing but healthy based on what? If you’re on a nandrolone base then cellular ratios are completely different so serum levels mean… not much?
...

There is more uncertainty. However, there are still hormones downstream of pregnenolone that have independent importance. DHEA, for example.

...
Deca base 300/wk
EQ is in and out
GH is in there as well.
...

As is pointed out in the YouTube comments section, the doctor erroneously ordered the immunoassay free T test, which reacted to the nandrolone. In reality his free testosterone is probably negligible. Interesting that the patient's subjective results weren't too bad. Still, he's wise to be getting off of that regimen.

 

[benaoao]

I’m aware that his free T is misinterpreted by the doctor. That’s not too relevant tho since total T LCMS comes back at 3 and some change

Dhea should be pumped out by the adrenals, however since it opposes cortisol at the receptor site and nandrolone also does that it’s expected to have lower levels of DHEA. Supply and demand. Furthermore, Dhea converts into estradiol so supplementing it while on Deca would lead to more estrogen dominance.

It’s some tricky stuff totally flipping over regular human biochemistry, and I think regular serum testing doesn’t apply in the context of a Deca base. It’s quite intuitive to understand. We do the same thing all the time with women who receive synthetic progestins and we certainly don’t try to get them all to whatever “normal” levels. If they feel good then rock n roll.

 

[benaoao]

I think prolactin should be used by default as a far superior indicator of dopaminergic vs serotoninergic and androgen/progesterone/estrogen activity. Being in the single digits shows that everything is in check and the guy is mostly doing fine, except for EQ skyrocketing his CBC

 

[Cataceous]

It’s a partial agonist, so it replaces progesterone while exerting a weaker effect. So that triggers estrogen dominance. Read up on partial agonists.

Do you have a source for this? Nandrolone has a lower affinity for the progesterone receptor than progesterone, which reduces its relative activity. But I've so far found nothing saying that the effect after binding is weaker. The relatively large doses of nandrolone seem sufficient to promote normal and above progestogenic activity.

 

[Gman86]

It’s a partial agonist, so it replaces progesterone while exerting a weaker effect. So that triggers estrogen dominance. Read up on partial agonists.

Progesterone supposedly inhibits aromatase and downregulates estrogen receptors. If nandrolone partially agonizes progesterone receptors, how would this create estrogen dominance?

 

[Gman86]

Do you have a source for this? Nandrolone has a lower affinity for the progesterone receptor than progesterone, which reduces its relative activity. But I've so far found nothing saying that the effect after binding is weaker. The relatively large doses of nandrolone seem sufficient to promote normal and above progestogenic activity.

So do u think someone on test with nandrolone would require less exogenous progesterone than someone on just test alone?

 

[Gman86]

@benaoao so if nandrolone replaces progesterone at the prog receptor, and exerts a weaker effect, does this mean it can block actual prog, endogenous or exogenous, and therefore a person using nandrolone would require more exogenous prog to get the same effect as someone not on nandrolone and say on test alone?

 

[Cataceous]

Progesterone supposedly inhibits aromatase and downregulates estrogen receptors. If nandrolone partially agonizes progesterone receptors, how would this create estrogen dominance?

The idea is that nandrolone is competing with endogenous progesterone to bind at the progesterone receptors. It only has 20% or so of the binding affinity of progesterone, but in sufficient amounts it would be displacing some progesterone from the receptors. If nandrolone activates the progesterone receptor as much as progesterone then the displacement of progesterone doesn't matter in terms of overall activity. But if nandrolone is weaker than progesterone in receptor activation, as claimed by @benaoao, then it's possible for overall progestogenic activity to be reduced. However, sources such as Wikipedia refer to nandrolone as "a potent progestogen", and also list it as a PR agonist without qualification.

Furthermore, there are anecdotal reports that some guys who take only nandrolone supplement with estradiol. You'd think that would not be a viable strategy if nandrolone were already increasing estrogenic activity.

So do u think someone on test with nandrolone would require less exogenous progesterone than someone on just test alone?

Yes, I think this is likely. Of course this assumes there's not additional suppression of endogenous progesterone caused by the nandrolone. Otherwise, assuming nandrolone is a full agonist of PR, then you could multiply the weight of the nandrolone you're taking by some factor, maybe 20%, and view that as the equivalent amount of progesterone you're getting.

Was just listening to a podcast this morning where the guy from Ray peats forum, Haidu, was mentioning how progesterone has some aromatase inhibiting properties, as well as downregulates estrogen receptors, just like u said. He also said vitamin E does these two exact things as well. Have u ever heard or read about vitamin E inhibiting aromatase and downregulating estrogen receptors?

I have seen that post, which says that vitamin E can antagonize estrogen receptors, inhibit aromatase, and also down-regulate aromatase expression. Of course it also says that "Vitamin E reduced androgen signaling without affecting androgen metabolism." This could be counterproductive.