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Dear Mark: Pregnenolone

In today’s edition of Dear Mark [1], 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 [2] 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 [3] 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 [4] 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 [5] functional capacity (but not cognitive function). Another study [6] 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 [7].

Pregnenolone regulates the connections [8] 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 [9], 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 [10]. This can limit the effects [11], and supplemental pregnenolone may be able to reduce cannabis-induced impairments to cognitive function and social interactions [12].

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.

References:

Akamatsu T, Chiba H, Kamiyama H, Hirose K, Saito H, Yanaihara T. Menopause related changes of adrenocortical steroid production [3]. 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 [4]]. 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 [5]. 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 [6]. 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 [7]. 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 [8]. 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 [9]. Biol Psychiatry. 2013;73(11):1045-53.

Vallée M, Vitiello S, Bellocchio L, et al. Pregnenolone can protect the brain from cannabis intoxication [13]. Science. 2014;343(6166):94-8.

Welberg L. Addiction: pregnenolone limits effects of cannabis [11]. 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 [12]. Mol Psychiatry. 2017;22(11):1594-1603.