So many people taking pregnenolone!
I posted recently that I personally didn’t use it in my patient population because I didn’t feel that there was good research in humans to support its use. So I thought I would return to the literature to see if this still held true. I’ll show you what I’ve found below.
Additionally, I tend not to use the hormone because of where it sits in the “hormone cascade.” Recall that we make our sex and adrenal hormones using cholesterol as a precursor. This sits on the very top of the cascade hill, and it is immediately converted to pregnenolone.
Don’t Confuse Hormone Replacement with Game Theory
Did you ever play a Pachinko game? If not, just Google one and you will know what I am talking about. When we give a hormone so high up on the cascade, we really don’t know where it is going to go. It can theoretically “pachinko” down to any number of different metabolites.
But what about Progesterone? It is the hormone immediately below pregnenolone. Don’t we use that all of the time? Wouldn’t it have a similar random, pachinko-like response?
That’s a good question, and I have pondered it myself. I think that in a woman, progesterone is simply used more. It has more cell-based actions, particularly around management of the uterus and menstrual cycle. So it gets consumed as progesterone before it travels down the pathway.
I recalled having done a literature search not too long ago looking for human trials on pregnenolone, and feeling that there weren’t many. I looked again today and confirmed this. There was one paper (cited below) that had a relatively good design that showed that there was some improvement in depression in patients treated with pregnenolone.
But this was only in one of the metrics used, the IDS-SR. The other test used, the HSRD, didn’t show an improvement.
There is a lot of bench research—looking at cells, biochemical pathways and other things that happen in test tubes and petre dishes. And there are plenty of mouse and animal trials. But there are not so many clinical trials of pregnenolone on humans.
Bottom Line: Pregnenolone is Not my First Choice for Hormone Replacement
My bottom line is to not use this hormone because in my patient population, particularly my fatigued patients, I find that I often have so many other things to focus on. I try to be clean and directed with my medication and supplement use. I’d rather have a patient use three focused treatments than handfuls of supplements of unknown quality and unknown drug-drug interactions. Cost, safety, practicality—all of these factor into this decision.
But if you are using pregnenolone, feel great, and have either clinical or measured evidence of balanced hormonal function in all of the “downstream” hormones. I’d say keep on using it.
It is pretty safe, and like the saying goes:
“If it ain’t broke, don’t fix it.”
Neuropsychopharmacology. 2014 Nov; 39(12): 2867–2873. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression