Dear Mark: Pregnenolone

In today’s edition of Dear Mark, I’m talking about pregnenolone, the “master hormone.” Most of the hormones we talk about, like testosterone, estrogen, and cortisol, all have pregnenolone as their precursor hormone. What can happen when pregnenolone goes too low? Can taking pregnenolone solve any problems? Is menopause actually a pregnenolone deficiency?

Let’s find out….

Referring to the “precursor hormone” pregnenolone, AJ requested:

I want to know more about this!
Mark – please do a post about this.

How about a Dear Mark answer?

Let’s get this out of the way: For menopause, I’m not sure if pregnenolone is the solution, or if low pregnenolone is even a problem. A 1992 study examined the basal hormone levels of women of varying ages, including reproductive, premenopausal, and postmenopausal. As age increased, levels of all hormones dropped—except for pregnenolone. They had plenty of precursor hormone. They just weren’t converting.

Another study seems to confirm. They compared hormone levels of postmenopausal women, women who’d had their ovaries removed, and a control group. Only the group without ovaries had low pregnenolone levels (cholesterol conversion to pregnenolone occurs in the ovaries). The other two groups, including the postmenopausal women, had normal levels.

That’s not to say pregnenolone isn’t useful. It is the precursor to the various steroid hormones, so if for some reason you’re low in pregnenolone, you’ll probably be low in testosterone, estrogen, and progesterone. Some of those symptoms could feel an awful lot like menopause.

Pregnenolone may help other conditions, for what it’s worth.

In patients with schizophrenia, pregnenolone supplementation improved functional capacity (but not cognitive function). Another study combined pregnenolone with L-theanine, the anti-anxiety compound found in green tea, finding that the combination reduced anxiety and other negative symptoms in schizophrenia patients. It can also help recent-onset schizophrenia patients.

Pregnenolone regulates the connections between your amygdala—the emotional center of the brain—and the rest of your brain. If pregnenolone is too low, the connectivity goes wild, triggering fear and anxiety; giving pregnenolone reduces this connectivity and quells the anxiety. If only as a basic emotional regulator, pregnenolone appears useful.

Pregnenolone is useful in the context of cannabis use. When THC hits cannabinoid receptors in the brain, the brain upregulates pregnenolone production to regulate intoxication. This can limit the effects, and supplemental pregnenolone may be able to reduce cannabis-induced impairments to cognitive function and social interactions.

Pregnenolone is clearly helpful and important, but, perhaps, not in most cases of menopause. If menopause coincides with low pregnenolone levels, by all means try it.

Now let’s hear from you. Have any of you seen results with pregnenolone? Has it helped with menopause, or any other condition?

Thanks for reading, and take care.


Akamatsu T, Chiba H, Kamiyama H, Hirose K, Saito H, Yanaihara T. Menopause related changes of adrenocortical steroid production. Asia Oceania J Obstet Gynaecol. 1992;18(3):271-6.

Ohta H, Nozawa S, Nemoto K. [Influences of menopause and oophorectomy on sex steroids secretion and metacarpal bone mineral content]. Nippon Sanka Fujinka Gakkai Zasshi. 1991;43(2):213-20.

Marx CE, Lee J, Subramaniam M, et al. Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. Psychopharmacology (Berl). 2014;231(17):3647-62.

Kardashev A, Ratner Y, Ritsner MS. Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Schizophr Relat Psychoses. 2018;12(1):31-41.

Ritsner MS, Bawakny H, Kreinin A. Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial. Psychiatry Clin Neurosci. 2014;68(6):432-40.

Sripada RK, Welsh RC, Marx CE, Liberzon I. The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity. Hum Brain Mapp. 2014;35(7):3249-61.

Sripada RK, Marx CE, King AP, Rampton JC, Ho SS, Liberzon I. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol Psychiatry. 2013;73(11):1045-53.

Vallée M, Vitiello S, Bellocchio L, et al. Pregnenolone can protect the brain from cannabis intoxication. Science. 2014;343(6166):94-8.

Welberg L. Addiction: pregnenolone limits effects of cannabis. Nat Rev Neurosci. 2014;15(2):66-7.

Busquets-garcia A, Soria-gómez E, Redon B, et al. Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice. Mol Psychiatry. 2017;22(11):1594-1603.

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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10 thoughts on “Dear Mark: Pregnenolone”

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  1. Something seems to be going on with the RSS feed. Didn’t get updates yesterday or today. Just deleted and resubscribed and only get the previous 10 stopping at Saturday. Anyone else having this issue?

    1. Yea, the site’s acting weird. On my phone, posts from June are popping up on the site’s “latest posts” feed; gotta refresh to get the actual lastest posts.

  2. I took pregnenalone under the care of an acupuncturist due to low hormone levels from endometriosis and adrenal fatigue. But it pas part of a cocktail that included DHEA, melatonin, licorice, 5-HTP, l-tyrosine, and a strong pack of vitamins and fish oil. Started feeling better after a couple of months and was able to get pregnant. I was 36 at the time so not in menopause but my estrogen levels were at premenopausal levels.

  3. What? No pregnenolone and men section? Like DHEA does it not have a roll in men’s hormones?

  4. I’m a 46 year old male. I take between 50-150mg per day 4-5 days per week. I take it because it seems to have the effect of blunting stress from my job. I don’t get stressed or anxious and am better able to deal with problems. My libido is improved. Other “things” work way better – like I’m 20 again. It definitely helps me and even though I’ve read plenty about it, I am not sure exactly why it seems to work well for me.. I take it mainly in the evening. Recently I began taking resveritrol with it and am keeping my preg dose around 50mg per day. This seems to work well with good sleep, mood, low stress, etc.

  5. I knew about the THC pot thing only after I noticed it completely blocked my high and did research on it. If I have supplemented that day, I can’t get even remotely head high. Even with double my usual dose that I occasionally use for nausea and sleep. I feel it in the body but nothing in the brain. It’s pretty incredible. Don’t take if you actually want to be high. Wastes your money!

    1. Ok so pregnenolone is good me… a man.. to reduce anxiety? And I won’t grow breasts? ? Seriously though…

  6. I am a 46 year old woman, and for several years after about age 42-43 I was sufferring with nightly migraines that would wake me up at around 2am. I would sometimes have a couple of month break but then they would start up again. This was hugely disruptive to my life as I was taking excedrin every night because it was the only thing to get rid of the migraine, but the excedrin was causing my stomach lining to become inflamed and it was very painful, as well as my sleep being interupted nightly.

    No doctors were helpful, honestly most of them just shrug their shoulders and profess that migraines are a mystery.

    After searching and searching, I finally came across one tiny little tidbit of info that made all the difference for me. It seems that in perimenopause it is common for estrogen to swing around, and often it dips drastically in the wee morning hours. A drastic dip in estrogen can trigger a migraine.

    I immediately began taking a pregnonolone with dhea supplement, and the nightly migraines stopped with the first dose. I get an occasional middle of the night migraine, perhaps once a month or so, but the effect was immediate. Also I am much more even tempered. I was mood swinging prior to this supplement and my poor kids were taking the brunt of that. Now I am much more reasonable except that 2 days or so before my period where I am on edge, hate the world and have zero patience. So business as usual ?

    1. do you take this dhea/pregnonolone at night before bed , or in morning?