Chris Kresser: There’s still a whole lot we don’t understand about pregnenolone and particularly about DHEA. I mentioned that in the unit because it’s very difficult to study DHEA in animals. It’s not produced in the same way in animals that it is in humans, and so all of the ways that we rely on studying hormones in animals, we can’t do that with DHEA, so it’s a little bit of a black box. Pregnenolone, as I mentioned, is a neurosteroid. It does play important roles in the brain and in the nervous system overall and in the HPA axis in particular, and it is the mother of all hormones in that it’s used for synthesizing these different hormones, but the thing that we need to get away from is this idea that there’s just one pool of pregnenolone in the adrenal glands that is used to synthesize all the hormones and if that pool is sort of drained to produce cortisol, then not enough will be left over to produce other hormones. That’s the part that’s incorrect.
In terms of what’s actually happening and what do we do with that information, the studies have shown that supplementing with DHEA and pregnenolone don’t tend to raise levels of downstream hormones like estrogen and progesterone, so using it in that fashion is probably not what provides the benefits that some people see when they take pregnenolone. There are some studies that have shown that pregnenolone supplementation may be beneficial, but that’s probably due to its effects as a neurosteroid rather that as a kind of precursor material for producing downstream hormones.
Having said all that, because of the role that pregnenolone plays in hormone production and HPA axis function, it’s certainly reasonable to assume that it is affected by stress and HPA axis dysregulation. It’s just that from a clinical and therapeutic perspective, we don’t have a lot of information on whether measuring pregnenolone levels affects the course of treatment and what to do with pregnenolone supplementally.