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haidut

haidut

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Well, apparently pregnenolone (at least taken orally) will convert around 50% to progesterone, so maybe the antiandrogenic results some people is seeing with pregnenolone (discussion here) is not only because of the progesterone conversion but also because of the progesterone conversion to allopreg and then causing GnRH inhibition. I'm starting to suspect that these kind of problems do not depend that much about the dose "per se" but depend on a ratio, like if you have a good endogenous production of androgens (or taking them exogenously) to oppose all that antiandrogenic activity.

I agree, and that is why I think it is important to add DHEA or another androgen to pregnenolone/progesterone. Pregnenolone actually may be OK as in lower doses it does seem to favor both the DHEA and the proegsterone route and only in higher doses does it become predominantly progesteronic. But if only progesterone is taken then I would definitely add DHEA and ideally DHT.
 

Quality

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What????? Testicular shrinkage from pregnenolone? Where do you get that from? Please share whatever info you have on that!

Im not saying it does, I am ASKING, and Im saying people seem to reluctant to give me information about it in general when I asked on other forums.
 

Quality

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If your question is specifically about 5a-DHP then the answer is that it does not seem to inhibit steroid synthesis except estrogen and prolactin, which should actually improve androgenic status. Yes, it does convert into allopregnanolone and that steroid may have antigonadotropic properties but the doses used in the animal studies (5mg - 7mg HED) are probably not achievable with 5a-DHP supplementation unless somebody takes 20mg -30mg. However, the doses used for the anti-depressive effects (1mg - 2mg HED) are achievable with a few milligrams of 5a-DHP.
Btw, adding just a little pregnenolone (1uM/L, so about 5mg - 10mg) completely overcomes the inhibitory effects of allopregnanolone on GnRH. So that could be an option for people experimenting with high doses, which is probably not advisable anyways as even the low doses of 5a-DHP (~5mg HED) were quite effective against estrogen and prolactin.
The neuroactive steroid allopregnanolone suppresses hypothalamic gonadotropin-releasing hormone release through a mechanism mediated by the gamma-aminobutyric acidA receptor

Interestingly, another study found that allopregnanolone actually increased GnRH release, even in non-stimulated conditions.
A progesterone metabolite stimulates the release of gonadotropin-releasing hormone from GT1-1 hypothalamic neurons via the gamma-aminobutyric acid ... - PubMed - NCBI

So, I think the jury is still out on whether allopregnanolone is suppressive or not.
Thanks man thats a great reponse, cause I couldnt imagine it would be bad and was a little shocked when I read the page about allopregnanolone.
It does make sense when you think about it, for example when someones estrogen is above their baseline (which is very common in the toxic environment we live in), a small dose of 5a-DHP/ALLO would be anti-estrogenic/mood enhancing, we all know that anti-estrogens have the possiblity to raise T (clomid/anastrazole etc for example).
 

Drareg

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haidut,

I hope you find some time to answer this question. Please follow me on this train of thoughts :

- When I say "feminizing" I use indistinctly for "anti-androgenic". Same thing for the matter.

- 5a-DHP is an agonist at progesterone and androgens receptors.

- 5a-DHP has been found to stimulate pregnenolone and progesterone production.

- You have said in other threads and also there's annecdotal evidence in this forum that progesterone can have anti-androgenic effects. Normally big doses but still people with moderate doses got feminizing effects. This also happens with pregnenolone, which shouldn't happen, but it happens. You said it so also. Probably via conversion to progesterone.

- You also said in another 5a-DHP thread it can have antigonadotropic properties.

- 5a-DHP doses of 5-6 drops should not convert to DHT via the alternative pathway, you need more in the range of 15-30 drops. It's written on this thread. This is the two modes of action of 5a-DHP. Doses inbetween seem to be not effective.

Following this train of thoughts (I hope I'm wrong), in certain individuals/hormone profiles like PFS or stuff like that, we might a cocktail for anti-androgenicity.

Then my question is : Is it possible that 5a-DHP has anti androgenic activity ? Wether systemical or in the brain. Because if it is a progesterone agonist, it could have feminizing effects. And maybe the androgen agonism is not enough to oppose that. At least if we're talking about 5-6 mg doses.

I'm asking you this because I used 5a-DHP for a couple of days and I felt much less interest in women. Less libido. More femenine attitude like less assertive, etc.

Also you mentioned in another thread that allopregnanolone can have anti-sexual effects. I'm not sure what do you mean by that. Just reduced libido ?

Other than that I must say this supplement is one of the BEST ones I ever tried for improving mood and cognition and energy levels. IMPRESSIVE. However I'm really worried about that antiandrogenic aspect. Maybe it was just coincidence but I'm very sensitive to these things and I pay a lot of attention to them and notice it right away. I hope you can chime in.
@Wagner83

Maybe you don’t need it,have you checked your levels or is it more just experimenting?
If under stress we look to increase said steroids you may still have this capacity and be in good health in this area so adding more might not be the way forward.
I think the past underlying and now current epigentic imprinting can’t be ignore either.

I’m not saying you here but some people look for miracles from substances over a week period,it’s crazy to think like that in most cases,people can have years of issues imprinted into the structure of the body and it’s not going to turn around in a week,for example if you lift weights it has been shown to improve DHT levels,you been active a certain way in the environment is looking to create new structure and the activity requires dht.
The mood lift is good but was your mood very bad to begin with? It’s like having a good week and being ok with it and then winning 1 million dollars tax free,you will be happier than previously in most cases but what do these feelings say.
 

ddjd

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rat took first 5 drop today and is experiencing some nausea and need to throw up. anyone elses rats experienced this?
 

ddjd

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I've been experimenting with different doses with my rat. I doses twice a day, starting with 1 drop, then 2, then 4, and today 8 drops in the morning. 1 and 2 drops were great for libido and calm, but increasing doses increase joint pains, diarrhea, nausea, irritability, irrational aggression, with decreased libido. I have seen many of these symptoms from my rat with high doses of vitamin E, so possibly there is too little estrogen or estrogen flushing from the cells. Maybe people that are not seeing results should try a lower dose.
i seem to got a nausea reaction also, are you still having this issue
 

Pointless

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i seem to got a nausea reaction also, are you still having this issue

I seem to get it with AIs. Letting my milk warm up a little outside the refrigerator for 10-15 min. has helped, but I don't know if that applies to your situation. Watch out for Lisuride and Metergoline.
 

Frankdee20

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It would be feasible but I think that if GABA-A agonism is your main goal there are plenty of other substances that are just as potent and also OTC. Aside from progesterone, which is a potent GABA-A agonist, the amino acids theanine and taurine are also very good at GABA agonism. Some androgens like androsterone and its metabolites are also pretty good as GABA agonists. I am wary of the 5-AR glucocorticoids as there is some evidence that despite being weaker glucocorticoid agonists than cortisol, they are still capable of doing it and thus causing metabolic issues. But I will look into it.
Oh, one last thing - pregnenolone in the lower doses that you use it a GABA agonist as well. Only the higher doses may cause some insomnia and agitation as a big pregnenolone dose gets converted into pregnenolone sulfate (PS) and the PS is antagonist at GABA. So, you should probably keep the physiological doses pregnenolone and maybe try some theanine with them. Even 200mg theanine seems to have potent GABA-ergic effects.

To your knowledge, would any of these, Taurine, low dose Pregnenalone, Theanine, Progesterone, cause GABA downregulation from the agaonism ? Would that not apply if they're indirect GABA boosters like Theanine ?
 

Andman

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You are more than welcome. I have not experienced such dramatic effects with continued usage so I have been trying to cycle it.

It does bring a sense of calm but I can feel the anti estrogenic effects fairly quickly. If I dose too much I notice sleep becomes worse, this is usually a very low e2 side for me. I am wondering if I managed to have all of my other hormones in a better balance, 5a DHP would work its magic much better!


@haidut Your knowledge on hormones seems extensive and I am trying my best to study your posts as much as I can.

Since coming off of HCG and TRT I have felt like ***t. Initially I felt better then seemed to have crashed. The confusing thing for me is I have extremely high SHBG (in the 70's) and very low free T and low E2. I have not had any sexual functioning in 3 months now. My testes do not feel atrophied. I did have my LH and FSH checked once coming off TRT and they had recovered. I am just wondering as to why I am left with this high SHBG with such low E2.

All I can find on high SHBG is liver issues (which I do not seem to have) and raised E2. Now with high SHBG does that mean I potentially have even lower free E2? My joints are cracking and popping, skin is really dry, sleep not as good although the right dose of 5a DHP really does help!

I know you are not a Dr and I appreciate it would be best to have a Dr's opinion. The only problem is I am in the UK and Endo's and GP's are completely clueless. Last endo I saw told me men did not need Estrogen and that SHBG was irrelevant seen as my total T was acceptable.


I am desperate to feel well. Thank you again. This forum is such a help!

Kinda sounds like my situation a lot, Test & HCG never made me feel much better..over time i became more and more robotic/asperger-like. (Athlethic benefits were obviously huge however, also improved confidence etc) - after quitting there was an initial improvement, afterwards back to normal. doing PCT right now.

5a-DHP also helps me a great deal in the ways you describe, however these effects are not permanent unfortunately :(

@haidut Seeing as it is a progestin, this would fit strangely well with gbols theory no?
 
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To your knowledge, would any of these, Taurine, low dose Pregnenalone, Theanine, Progesterone, cause GABA downregulation from the agaonism ? Would that not apply if they're indirect GABA boosters like Theanine ?

I think only taurine has so far had reports of "withdrawal" due to GABA downregulation, and that was in doses of 5g+ daily. In theory others can cause it too but I have not heard complaints after stopping say progesterone.
 
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haidut

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Kinda sounds like my situation a lot, Test & HCG never made me feel much better..over time i became more and more robotic/asperger-like. (Athlethic benefits were obviously huge however, also improved confidence etc) - after quitting there was an initial improvement, afterwards back to normal. doing PCT right now.

5a-DHP also helps me a great deal in the ways you describe, however these effects are not permanent unfortunately :(

@haidut Seeing as it is a progestin, this would fit strangely well with gbols theory no?

What would be his theory on progestins?
 

Frankdee20

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I think only taurine has so far had reports of "withdrawal" due to GABA downregulation, and that was in doses of 5g+ daily. In theory others can cause it too but I have not heard complaints after stopping say progesterone.

Thank you, I did see that Taurine thread.
 

Frankdee20

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Some other thread on this forum has an excerpt on how Pregnenalone agonized GABA and cases down regulation.
 

Quality

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Taurine raises my libido to annoying high proportions especially at 2-3 grams twice a day.
Instead of doing work at work I keep fantasizing about female colleages and makes me feel way too uninhibted, bit like a low dose alcohol with beneficial health effects. Oil for my soul so to speak.

Pregnenolone itself was junk for me, after my experience yesterday with 2.5mg sublingual I have decided not to touch that ***t again untill someone can convince on a dose that would raise GABA as 2.5mg definatly was anxiogenic for me after ~2hours of intake, the first 2hours It was ok, but after 2hours, its trash for me.
Are there any people on here that have experience with pregnenolone, progesterone and 5a-DPH and can give some side by side comparison on how they affected them.
 

Frankdee20

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Taurine raises my libido to annoying high proportions especially at 2-3 grams twice a day.
Instead of doing work at work I keep fantasizing about female colleages and makes me feel way too uninhibted, bit like a low dose alcohol with beneficial health effects. Oil for my soul so to speak.

Pregnenolone itself was junk for me, after my experience yesterday with 2.5mg sublingual I have decided not to touch that ***t again untill someone can convince on a dose that would raise GABA as 2.5mg definatly was anxiogenic for me after ~2hours of intake, the first 2hours It was ok, but after 2hours, its trash for me.
Are there any people on here that have experience with pregnenolone, progesterone and 5a-DPH and can give some side by side comparison on how they affected them.

I was also skeptical about Pregnenalone after my initial trial at 10mg oral, for a few days. I didn't notice that calmness I wanted, it was stimulating and felt like it converted to stress hormones. Gave me headaches too. Then, after a month hiatus, I was determined to try again. I split the capsule in food, never going over 5 mg a day here and there. One time, I was shocked to see how well it shut off a stress reaction. I noticed now it is very tolerable, even if one can't predict the pathway. I get DHEA like effects from it, even today, I took 5 mg at noon, orally. My voice gets deeper, brow and gaze get more "manly" like. I feel okay, not sedated. Sometimes it would just make me tired. But I'm accustomed to the dosing now, I like it. I wonder if I go up to 10mg again how I'll respond. So at best, the conversion is variable. In ten times I've taken it, 4-5 were stimulating, 2-3 relaxing, 2-3 slightly DHEA like.
 

Frankdee20

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Taurine raises my libido to annoying high proportions especially at 2-3 grams twice a day.
Instead of doing work at work I keep fantasizing about female colleages and makes me feel way too uninhibted, bit like a low dose alcohol with beneficial health effects. Oil for my soul so to speak.

Pregnenolone itself was junk for me, after my experience yesterday with 2.5mg sublingual I have decided not to touch that ***t again untill someone can convince on a dose that would raise GABA as 2.5mg definatly was anxiogenic for me after ~2hours of intake, the first 2hours It was ok, but after 2hours, its trash for me.
Are there any people on here that have experience with pregnenolone, progesterone and 5a-DPH and can give some side by side comparison on how they affected them.

I should also mention that sublingual has more affinity to go down unconverted pathway as PS, which is stimulating anyway. Perhaps, topical or oral before you give up ?
 

Quality

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Yeah thats what I did, broke a source naturals 10mg pregnenolone pill in quarters, crushed the piece with the back of a spoon on a plate, put the powder under my tongue for ~15mins, then choked down the remains with water, after about 2hours, get pressure on both sides of my head, left and right and getting anxious, first 2hours i felt as if it made me somewhat calm though.

Could it be that my body burned through the 2.5mg within the first 2hours, leaving me 'drained' afterwards.

I want to try progesterone and 5a-dhp next unless theres another kind of protocol for me to use pregnenolone.
Looking for the emotional benefits by the way for which progesterone apparantly seems to fit me better from what Ive read, I got no libido problems at all.

The women I hang around with often say im too rude, I just end up having sex with them and then end of the day I still dont have a relationship and most of the days im alone in the evening.
I also get frustrated when I see 'happy families' with kids n stuff, guess im jealous? idk, anyway I feel as if either progesterone/5a-dhp got me more to offer than pregnenolone.
 

Frankdee20

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Yeah thats what I did, broke a source naturals 10mg pregnenolone pill in quarters, crushed the piece with the back of a spoon on a plate, put the powder under my tongue for ~15mins, then choked down the remains with water, after about 2hours, get pressure on both sides of my head, left and right and getting anxious, first 2hours i felt as if it made me somewhat calm though.

Could it be that my body burned through the 2.5mg within the first 2hours, leaving me 'drained' afterwards.

I want to try progesterone and 5a-dhp next unless theres another kind of protocol for me to use pregnenolone.
Looking for the emotional benefits by the way for which progesterone apparantly seems to fit me better from what Ive read, I got no libido problems at all.

The women I hang around with often say im too rude, I just end up having sex with them and then end of the day I still dont have a relationship and most of the days im alone in the evening.
I also get frustrated when I see 'happy families' with kids n stuff, guess im jealous? idk, anyway I feel as if either progesterone/5a-dhp got me more to offer than pregnenolone.

Give it a shot, you'll go down direct route. Yeah, I tend to have meaningless sex too, and I wouldn't change a thing. Sincerely, shallow Hal
 

Koveras

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I think only taurine has so far had reports of "withdrawal" due to GABA downregulation, and that was in doses of 5g+ daily. In theory others can cause it too but I have not heard complaints after stopping say progesterone.

@Frankdee20 @haidut

"Research on progesterone withdrawal syndrome has shown that progesterone withdrawal causes anxiety, moodiness, and depression due, in large part, to its GABA-A receptor interactions (Rupprecht, 2003; Gulinello et al., 2003; Smith, 2002; Kulkarni and Reddy, 1995). Of the many possible side effects in humans, PW can cause anxiety, mood swings, depression, increased seizure susceptibility, and excitotoxicity (Rupprecht, 2003). These behavioral and molecular consequences of PW can inhibit both the short- and long- term contributions of a 5-day progesterone regimen to recovery after TBI, since the withdrawal symptoms are observed after as little as 4 days of treatment (Gallo and Smith, 1993)."

"In conclusion, although progesterone treatment decreases inflammation and apoptosis, acute withdrawal increases activity in some apoptotic and inflammatory pathways and increases anxiety behavior during the acute healing phase. A tapered withdrawal of the hormone further enhances short-term recovery after TBI."

Tapered progesterone withdrawal enhances behavioral and molecular recovery after traumatic brain injury. - PubMed - NCBI
 

Frankdee20

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@Frankdee20 @haidut

"Research on progesterone withdrawal syndrome has shown that progesterone withdrawal causes anxiety, moodiness, and depression due, in large part, to its GABA-A receptor interactions (Rupprecht, 2003; Gulinello et al., 2003; Smith, 2002; Kulkarni and Reddy, 1995). Of the many possible side effects in humans, PW can cause anxiety, mood swings, depression, increased seizure susceptibility, and excitotoxicity (Rupprecht, 2003). These behavioral and molecular consequences of PW can inhibit both the short- and long- term contributions of a 5-day progesterone regimen to recovery after TBI, since the withdrawal symptoms are observed after as little as 4 days of treatment (Gallo and Smith, 1993)."

"In conclusion, although progesterone treatment decreases inflammation and apoptosis, acute withdrawal increases activity in some apoptotic and inflammatory pathways and increases anxiety behavior during the acute healing phase. A tapered withdrawal of the hormone further enhances short-term recovery after TBI."

Tapered progesterone withdrawal enhances behavioral and molecular recovery after traumatic brain injury. - PubMed - NCBI

That's a bummer man, I guess the only things that don't cause downregulation of a neurotransmitters are raw precursors (Glutamine, Tyrosine, Tryptophan, Aspartic Acid, Choline) then use cofactors for increased synthesis via Glutamic Acid Decarboxylase, Dopamine Hydroxylase, etc. Doesn't this bypass direct agonism of a receptor?
 

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