Pregnenolone and Progesterone not coupled in Bloodwork's.
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I (M 25) started taking pregnenolone (25-50mg daily) and DHEA (5-10 mg) a few weeks back. I chose Preg over Prog because that seems to be consensus peat advice for men and a lot of it should convert to Progesterone anyhow. Imagine my surprise to get bloodwork back a couple of days ago, and it's telling me Pregnenolone is off the charts (8,5 ng/ml), and progesterone is almost nonexistent (0,7 ng/ml). Oestradiol is low which is nice and I think tracks with my experience on the supplements, Test and DHEA are both fine. I've looked through both forums and haven't been able to find anything similar so far, my best assumption so far is that either the preg to prog conversion is messed up (3β-HSD problem?), which might go against the low oestradiol though, or progesterone is converting immediately further which would prob mean cortisol is off the charts - unfortunately its not in my bloodwork-, which would track with my stressed out state atm. Any ideas for explanation or treatment would be greatly appreciated.
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Ok so after some more research, there seems to be a thing called Pregnenolone steal where it all goes into cortisol. Which would align with my second intuition. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684134/) This is messed up, my body is robbing me.
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Haidut seems to believe theres no such thing, but hes also talking about DHEA/cortisol connection, and that most people with Pregnenolone Steal dont have low Progesterone, which I clearly have. Since Preg is anti-cortisol, should I just try a bigger dosage?
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Dr Peat responding to the Pregnenolone 'Steal' Theory
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@Peatly Thank you this is very interesting, from what I understand from that, Ray speaks against Pregnenolone Steal as a regular direct mechanism, but acknowledges that in a stressed system, lacking thyroid for example, the system can turn to converting most pregnenolone to cortisol.
"sometimes the stressed system is able to sustain only cortisol and aldosterone production, and that leads to degenerative problems."
Which is what I would assume is happening then. Its good to be aware of how things like thyroid etc. affect and regulate this mechanism, but in principle, if I read him right, the body is still "stealing" all the preg for cortisol production.
Ill try progesterone directly to adress this.
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I asked PeatBot about the Pregnenolone Steal:
User: what is Pregnenolone steal
Peatbot: Pregnenolone steal is a concept that suggests when the body is under stress, it preferentially diverts pregnenolone, which is a precursor to various steroid hormones, to produce cortisol, the stress hormone. This diversion is thought to occur at the expense of other hormones that pregnenolone could otherwise help synthesize, such as progesterone, DHEA, and subsequently, the sex hormones like testosterone and estrogen.
The idea is that in a state of chronic stress, the body's need for cortisol increases to manage the stress response. Since pregnenolone is the starting material for the synthesis of all steroid hormones, it is "stolen" or shunted towards the production of cortisol and away from the production of other hormones, potentially leading to imbalances or deficiencies in these other hormones.
However, Dr. Peat, in the context provided, seems to suggest that the body should normally have a surplus of pregnenolone and progesterone, and that only small amounts of the downstream hormones like cortisol and estrogen should be made as needed. He implies that pregnenolone and progesterone are stabilizing materials rather than hormones with direct effects, except for pregnenolone's role in helping tissues release excess water and regain normal tone in connective tissue. Dr. Peat's perspective appears to challenge the notion of pregnenolone steal as a significant concern under normal physiological conditions.
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@mouse I didn't interpret his response as agreeing with the idea of a ‘steal’. Peatbot is pretty close, thanks @DavidPS
Ray Peat - From Pms To Menopause
“Many steroids have a protective ("catatoxic") action against a wide variety of poisons. Some of the quick effects (e.g., within 10 minutes) of progesterone and pregnenolone probably represent a
catatoxic action, as well as a neutralizing or balancing of excessive estrogen or cortisol. Improved metabolic efficiency, sparing oxygen and glucose, will have a quick effect in reducing edema.”The question is do you have a clean source of pregnenolone?
Anyway, at the age of 25 do you need to be supplementing hormones? Dhea is particularly risky to supplement.
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@Peatly I will try to get a cleaner preg supplement, but since my preg bloodwork is way up, it seems to be working at getting in the body at least. Whats the DHEA risk with such low dosages?
How do you interpret this quote?
"sometimes the stressed system is able to sustain only cortisol and aldosterone production, and that leads to degenerative problems."I struggle to understand it as anything else but in certain circumstances, cortisol can dominate the hormonal pathways.
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@mouse Many things can stress the system. It probably means the person doesn’t have the resources to produce the protective hormones, progesterone and pregnenolone. If blood sugar is low this will increase cortisol and if sodium is low, aldosterone. High estrogen will increase cortisol. Hypothyroidism...........etc.
"By the 1930's, it was well established that the resistance of the
organism depended on the energy produced by respiration under the influence of the thyroid gland, as well as on the adrenal hormones, and that the hormones of pregnancy (especially progesterone) could substitute for the adrenal hormones. In a sense, the thyroid hormone is the basic antistress hormone, since it is required for the production of the adrenal and pregnancy hormones." FROM PMS TO MENOPAUSEPregnenolone is relatively safe if the source is clean.
Dr Peat on DHEA. This discussion is age specific but I think it might apply to younger men too.
He talks favourably of it in this interview so you need to weight up the benefits vs. the risks
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Why are you taking these in those higher doses and what have the effects been? If its just making you stressed more, you should lower or stop taking them for a while.
