5α-Dihydroprogesterone (5α-DHP) - The Primary Progestogen Neurosteroid

It has been shown that progesterone rapidly metabolizes into more saturated metabolites such as 5α-Dihydroprogesterone (5α-DHP) and tetrahydroprogesterone (also known as allopregnanolone or Allo). The enzyme 5-AR is the one responsible for the saturation, just as it is responsible for the conversion of T into DHT. The saturation metabolism of progesterone happens predominantly in the brain, and also during pregnancy. It has been shown that at least in the brain, it is the saturated progesterone metabolites such as 5α-DHP and Allo that are responsible for the vast majority of the beneficial effects ascribed to progesterone. Administering progesterone together with a 5-AR inhibitor such as finasteride or dutasteride almost completely abolished the beneficial effects of progesterone in the brain and peripheral nervous system. Most successful SSRI drugs are actually potent stimulators of Allo synthesis and it has been shown that saturated progesterone metabolites like 5α-DHP and Allo share the same beneficial CNS properties as progesterone, while often being considerably more effective and in lower doses. These properties include GABA agonism, glycine channel activator, anti-excitotoxic, anti-depressant, anti-seizure, protection from neurodegenerative conditions, recovery from trauma and injury (especially TBI), radiation protection, and last but not least powerful anti-aging effects in the brain.
The studies below focus on the saturated progesterone 5α-DHP and demonstrate that it may in fact be the primary progestogen neurosteroid.

Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features. - PubMed - NCBI
"...Many of the effects of PROG are due to its metabolites, DHP and THP (allopregnanolone). For instance, these two PROG metabolites mediate the protective action of PROG against excitotoxicity (Ciriza et al. 2006), THP reduces seizures (Frye and Scalise, 2000) and exerts protective effects in stroke (Sayeed et al., 2006), oxygen-glucose deprivation (Ardeshiri et al., 2006) and TBI (Djebaili at al. 2005). THP is also a potential candidate for the treatment of mood and anxiety disorders (Wirth, 2011)."

Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone aceta... - PubMed - NCBI
"... In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone."

Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone aceta... - PubMed - NCBI
"...Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5alpha-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3alpha-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone."

The Anticonvulsant Effects of Progesterone and 5α-dihydroprogesterone on Amygdala-kindled Seizures in Rats - Lonsdale and - 2003 - Epilepsia - Wiley Online Library
"...Conclusions: Progesterone is anticonvulsant only at high doses when tested against amygdala kindled seizures. 5α-dihydroprogesterone is considerably more potent than progesterone. At low, nonsedative doses, it was effective against both the kindled amygdala focal afterdischarge and the generalized convulsion."

Pregnancy without progesterone in horses defines a second endogenous biopotent progesterone receptor agonist, 5α-dihydroprogesterone. - PubMed - NCBI
The anticonvulsant effects of progesterone and its metabolites on amygdala-kindled seizures in male rats. - PubMed - NCBI
Effects of progesterone derivatives, dihydroprogesterone and tetrahydroprogesterone, on the subependymal layer of the adult rat. - PubMed - NCBI
Reduced progesterone metabolites protect rat hippocampal neurones from kainic acid excitotoxicity in vivo. - PubMed - NCBI
The anticonvulsant effects of progesterone and 5alpha-dihydroprogesterone on amygdala-kindled seizures in rats. - PubMed - NCBI
The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders. - PubMed - NCBI
Neuroendocrine metabolism of progesterone and related progestins. - PubMed - NCBI
Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. - PubMed - NCBI
Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum. - PubMed - NCBI
Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation. - PubMed - NCBI
Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is the metabolite responsible for anesthesia induced by 5 alpha-pregnanedione in the mouse. - PubMed - NCBI

 

Would an allopregnenolone product be next ?

 

I was thinking about it, but it is legally risky as I explained in the master thread on 5a-DHP. Quite a few companies are running clinical trials with allopregnanolnone proper and there is also the patented synthetic version called Ganaxolone. So, if any of the trials with it ends up with a socalled "new drug application" approval then FDA will start regulating it like a drug and it would be illegal to sell it. The 5a-DHP is much safer legally and has estrogen and prolactin blocking effects that allopregnanolone doesn't.

 

Haidut..Will 5α-DHP be available again anytime soon? I don't see it at the web site.

 

Bio-identical Allopregnenolone would be awesome to experiment with! Please re-consider haidut

 

I sent you a PM.

 

The majority of 5a-DHP quickly metabolizes into allopregnanolone. It has nowhere to go but to metabolize into allopregnanolone. Just as cholesterol has no where to go but pregnanolone. The allopregnanolone yield from 5a-DHP is upwards of 80%.

 

Thanks

 

My third day with the product... The rat is very relaxed... Heavy eyes while at work, but still able to think cleary... the rats penis appears Fuller and still had morning wood... And the rats pectorals are not bloated like they get on regular progesterone... So those are great positives. ...@Haidut, it seems that finasteride holds progesterone high, and disables 5-alpha enzyme from converting it to dhp... So the effects of hair growth are from high levels of progesterone , but the side effects of depression and sexual side effects are from high levels of regular progesterone without it being able to go to allo pregnenolone and DHP... Does finasteride lower prolactin levels though?

 

soo......finasteride stops progesterone converting into anything ?

 

That's what I'm speculating.. Haidut was saying that the 5 Alpha reductase enzyme converts progesterone into a allopregnenolone and other steroids Downstream... and since finasteride is a 5 Alpha reductase inhibitor, and also chemically identical to Progesterone, I'm thinking that by taking finasteride we're taking a synthetic progestin that does not get converted into other neurosteroids, which would then cause depression and mental disturbances... which finasteride does.

 

@tallglass13 are you currently taking anything else among with 5a-DNP? Any negatives to report?

 

I purchased most all the steroids but I took a break for two weeks prior to using the 5 DHP... at this time Im only using the 5DHP... and I only use the tiniest dosage of all of them so with the 5DHP I've only used two drops at most per day... maybe today I will do the 5 to 6 milligrams that's basically the minimum to lower prolactin 70%, but I believe I have at least lower prolactin 30 to 50% with the 2 milligram dosage... so I can't really report any negatives because I was feeling under the weather the last few days that might have Been related to my heavy eyes and tired feeling during the day. .

 

Excellent, thanks for the great feedback! Yes, finasteride does raise progesterone levels as it prevents conversion through 5-AR. I have long suspected that this is its main effect, which also suggests that combining finasteride with inhibitors for 17a-HSD and 3b-HSD will keep progesterone levels high as it would prevent it metabolism into any other steroid. So, that may boost hair growth even more.
The data on finsateride and prolactin is mixed. Some studies show it increases it while others show no effects. I think as long as you are producing decent amount of androgens like T every day then finasteride is not going to affect prolactin levels much. But if T synthesis is subnormal, then finasteride can make things worse by raising prolactin.

 

No, stops it just from converting down the 5-AR pathway. Other possible pathways are through 17a-HSD and 3b-HSD. So, inhibiting those as well would block progesterone metabolism and raise its levels. But blocking 5-AR alone is enough to elevate progesterone levels, which is probably what produces the beneficial effects no hair growth. Blocking all 3 enzymes (which can be dangerous) may increase hair growth even more. But no need to do dangerous stuff like that when you can just rub progesterone on the scalp.

 

The main thread on 5a-DHP has a link to its neurosteroid effects. As a few of the studies there say, administering 5-AR blocker like finasteride together with progesterone abolished almost all of the beneficial effects on the nervous system seen when administering progesterone. So, the path through 5-AR and thus 5a-DHP is crucial for progesterone to exert its beneficial effects through its metabolites like 5a-DHP and allopregnanolone. So, administering finasteride prevents the synthesis of 5a-DHP from progesterone, and hence allopregnanolone (which is synthesized from 5a-DHP). Without the 5-AR pathway metabolites, progesterone is mostly a pro-metabolic steroid.

 

I would be willing to test this topically. The thing is if the product is going to be discontinued I would probably not even start as it would be a committed treatment. I would also have to use a decent amount to cover the top of the scalp. If I did use topically can I dilute it some water or ethanol so I can spread it better? Also, do you think taking 5a-DHP orally at higher concentrations can promote hair growth?

 

The product is probably not going to be discontinued, but it will be sold with a disclaimer. If you go to the ordering website you will see a link with the title "disclaimer" under 5a-DHP. It leads to the thread with discussion on 5a-DHP and breast dysplasia. So, you can order it. We have a few decent supplier lined up for it so it should be stable product, just not a commonly used one like say EstroBan.
Not aware of any effects on hair growth and also since it is dissolved in tocopherol/MCT, if you want to dilute it should be with more MCT. Alcohol probably won't work as it does not mix well with oil.

 

Respect.

 

Excellent, that works fine with me. Glad it's still going to be available.