Significance of Progesterone & Its Receptor (PR)- Progesterone NOT Prolactin?

[Type-IIx]

I have a question regarding the significance of the Progesterone Receptor (PR) in humans, progesterone levels, and how these relates to commonly used AAS such as MENT (trestolone), Deca (nandrolone/19-nortestosterone), Tren (trenbolone).

My question is:

Progesterone Receptor (PR) in humans: it's been demonstrated by mammalian reporter gene bioassay that the aforementioned compounds bind quite strongly DIRECTLY to the PR. @PeterBond 's Book on Steroids cites research demonstrating progesterone "appears to control the proliferation and morphogenesis of the luminal epithelium of the breast" (Book on Steroids, p. 88) in women at least, yet states it is unlikely to cause male gynecomastia as clinically presented. However, anecdotes abound of pain, sensitivity, even lactation, which is probably worse.

It's not unheard of that these compounds are associated with erectile dysfunction in addition to lactation in men.

Perhaps because of PR in the brain? Assuming that it's not an aromatizable compound (test!) increasing E2 that's causing these issues, what is it about these compounds that worsen symptoms?

Is it that they act as substrates for E2 (the compounds themselves?) Or does interaction directly with the PR cause these problems (assuming not test)? or is it almost certainly the aromatizing compounds (i.e., test) that cause these problems?

Presumably bloodwork won't even reflect these interactions? Certainly not by prolactin values.

Another major question, do guys confuse prolactin and progestersterone? I know it is common for guys to use caber or lately p5p (a form of vitamin B) when running these compounds. I don't even think they can affect progesterone? If guys take caber or p5p, what are they accomplishing? These drugs do seem to do something for the embarrassing side effects mentioned I think, but how?

 

[Type-IIx]

I should have said "My questions are" rather than "My question is." Sorry about that!

 

[RoadToMrOlympiaClassicBb]

Hmmm no one that's sad!
However I'm currently on 200mg NPP for the first time and I suffer from insomnia -.- I cannot fa asleep and stay asleep. So would p5p help me? My sex drive is ok. Is it prolactin? Or something dopamine related I'm a bit confused about this and try to research this stuff!

 

[Jestopherson]

I've seen it noted that upregulation of the progesterone receptors can cause increased estrogen receptor expression. So even if your E2 Is in range it can cause gyno/ED. Along with the fact that for myself nandrolone does aromatize as I have blood work to compare.

I ran nandrolone earlier this year. No matter how much caber/p5p I threw at it, I still had ed and nipple sensitivity running a dose of test I don't need an AI for. I started running adex at 0.25mg 2x a week and eventually ended at 0.5mg 3x a week and all ED issues were Essentially dealt with with no low e2 sides yet running 600mg of test solo id crash my estro.

Furthermore I'm on 200mg cruise and I now need am AI for it due to high estrogen sides. Zesty nips, no morning wood, slight water retention, and decreased libido. So I'm wondering if the nandrolone metabolites are having a lasting impact on my progesterone receptors and directly affecting my e2 receptors. Now I do not have any literature on this, this is purely speculation, personal experience, and information gathered from others experiences.

Happy to be corrected or to continue the discussion.

 

[RoadToMrOlympiaClassicBb]

I've seen it noted that upregulation of the progesterone receptors can cause increased estrogen receptor expression. So even if your E2 Is in range it can cause gyno/ED. Along with the fact that for myself nandrolone does aromatize as I have blood work to compare.

I ran nandrolone earlier this year. No matter how much caber/p5p I threw at it, I still had ed and nipple sensitivity running a dose of test I don't need an AI for. I started running adex at 0.25mg 2x a week and eventually ended at 0.5mg 3x a week and all ED issues were Essentially dealt with with no low e2 sides yet running 600mg of test solo id crash my estro.

Furthermore I'm on 200mg cruise and I now need am AI for it due to high estrogen sides. Zesty nips, no morning wood, slight water retention, and decreased libido. So I'm wondering if the nandrolone metabolites are having a lasting impact on my progesterone receptors and directly affecting my e2 receptors. Now I do not have any literature on this, this is purely speculation, personal experience, and information gathered from others experiences.

Happy to be corrected or to continue the discussion.

It's strange I have no high e sides no itchy nipples and or problems with ed. I have only problems with insomnia! Where does it come from? Dopamine? Do you know the correlation. It's without doubt that it started after I got on NPP.

 

[Jestopherson]

It's strange I have no high e sides no itchy nipples and or problems with ed. I have only problems with insomnia! Where does it come from? Dopamine? Do you know the correlation. It's without doubt that it started after I got on NPP.

I honestly can't say! As caber is a dopamine agonist and it did nothing. I also tried PT141 which also affects dopamine responses and still nothing.

On npp I got insomnia, insane tren sweats. Like drenched everything even the pillow. And extreme mental sides.

Only thing that helped was AIs.

 

[Type-IIx]

Oh yeah, just after I wrote this Peter Bond put out an article (Regulation of Testosterone Production - MESO-Rx) explaining how progesterone and its derivatives affect hypothalamic regulation of T and gonadotropins via KNDy dendron signaling significantly versus serum prolactin.

wrt NPP and insomnia there are a lot of studies lately into the DA (reward system/dopamine) and AAS/including nandrolone; evidence of cyclothymia (fast-cycling, subclinical hypomania); nandrolone and apoptotic (cell death) mechanisms that seem involved in AAS-induced neurotoxicity.

 

[Type-IIx]

Oh yeah, just after I wrote this Peter Bond put out an article (Regulation of Testosterone Production - MESO-Rx) explaining how progesterone and its derivatives affect hypothalamic regulation of T and gonadotropins via KNDy dendron signaling significantly versus serum prolactin.

wrt NPP and insomnia there are a lot of studies lately into the DA (reward system/dopamine) and AAS/including nandrolone; evidence of cyclothymia (fast-cycling, subclinical hypomania); nandrolone and apoptotic (cell death) mechanisms that seem involved in AAS-induced neurotoxicity.

Looking at the research and connecting the dots with something Peter Bond said earlier, I am fairly certain that the "neurotoxicity" evidence is extremely weak, though I believe AAS exert influence on the GABA system. Also nandrolone isn't some particularly bad compound, it's just one they studied.

 

[RoadToMrOlympiaClassicBb]

I honestly can't say! As caber is a dopamine agonist and it did nothing. I also tried PT141 which also affects dopamine responses and still nothing.

On npp I got insomnia, insane tren sweats. Like drenched everything even the pillow. And extreme mental sides.

Only thing that helped was AIs.

So caber is a dopamine agonist. They tell us to use caber and this kind of drugs if we have problems with nandrolone so there must be a connection. Vit b6 or especially P5P goes this pathway. We'll see how my sleep behaves this days yesterday I took a pill to sleep because I really wanted to sleep after some days constantly waking up. Today is day two of 300mg P5P.

 

[RoadToMrOlympiaClassicBb]

Oh yeah, just after I wrote this Peter Bond put out an article (Regulation of Testosterone Production - MESO-Rx) explaining how progesterone and its derivatives affect hypothalamic regulation of T and gonadotropins via KNDy dendron signaling significantly versus serum prolactin.

wrt NPP and insomnia there are a lot of studies lately into the DA (reward system/dopamine) and AAS/including nandrolone; evidence of cyclothymia (fast-cycling, subclinical hypomania); nandrolone and apoptotic (cell death) mechanisms that seem involved in AAS-induced neurotoxicity.

Could you explain how it works that some guys get insomnia on nandrolone and what part exactly dopamine here? I really would like to understand the things which are going on in my body

What does nandrolone? It deplete dopamine? Downregulated thee receptors? I actually think the DR are upregulated!

 

[Type-IIx]

Could you explain how it works that some guys get insomnia on nandrolone and what part exactly dopamine here? I really would like to understand the things which are going on in my body

What does nandrolone? It deplete dopamine? Downregulated thee receptors? I actually think the DR are upregulated!

Rather than focusing on dopamine and receptors, the evidence on psychological effects of androgens tends to suggest dysregulation of the GABA system which could affect sleep/insomnia. There's experimental evidence in rats of beta-endorphin concentrations in the VTA increasing dramatically, implicating the reward system. There's evidence of the neuropeptide systems being affected. But all the research adds up to is a small fragment of disparate evidence on mostly short-term cognitive effects in rats.

It's also been postulated that the insomnia effects could be related simply to increased training stressors.

There does seem to be an association with cyclothymia, subclinical mania/depressive symptoms, and AAS. It could be that you're experiencing something akin to low-level mania OR it could be that the insomnia is related to increased training stressors.

 

[RoadToMrOlympiaClassicBb]

Hmm its a maniac, maniac
Thanks for the explanation!

 

[GreenAmine]

I'm currently on the 5th week of my third tren cycle (50 mg/day tren ace) and I decided on day 1 to try taking Seroquel to mitigate side effects. I'm a weirdo who doesn't get negative mental side effects from tren, only positive effects (better mood, decreased propensity toward anger), but the insomnia and profuse sweating made me stop my previous 2 cycles after 4 & 6 weeks, respectively. I also experienced some gyno issues like tenderness and itchiness, but introducing primo at 100 mg/week took care of that.

The Seroquel (25 mg every night) has eliminated all negative side effects from this cycle, and it's my heaviest tren cycle - the first 2 were 105 mg/week, and 210 mg/week, both tren ace dosed daily.

With relevance to this thread, I have experienced zero gyno issues, despite the higher dose and the fact that I'm running test higher (350 mg/week test C), 50 mg/day anadrol, and trestolone (25 mg EOD trest ace), the latter two of which historically cause gyno flare-ups for me. A wet cycle, I know, but water retention is never a problem for me. I recently dropped the anadrol and added primo, but not to control gyno, since that was not an issue. Seroquel, as well as other antipsychotics, are known to lower progesterone markedly:

Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder - PMC

www.ncbi.nlm.nih.gov

 

[Tmisatix]

Selective progesterone receptor modulators control progesterone aka Mifepristone which was originally used in cushings but now used to stop pregnancy. I don’t know how you’d feel crushing progesterone .. I do feel like many of the estrogenic type Sides on certain compounds may be due to progesterone so handling it may reduce AI burden

I think there’s some literature on aromasin having a slight prof lowering effect too

caber and prami probably do close to nothing in terms of progesterone