Pregnenolone – the little talked about hormone. In fact, it goes so unchecked that a LabCorp bloodwork slip doesn’t place a reference range of “normal” alongside the pregnenolone lab result. Now, the scarcity of practitioner-ordered pregnenolone inquiries may not be the true reason as to why a reference range of “low to high normal” is not well established, but it is interesting to note! And, to be fair, as an immediate disclaimer, World Link Medical training (from where my advanced bioidentical hormone therapy certification originates) also does not advocate for the routine checking of pregnenolone levels. They teach that pregnenolone research is somewhat weak in its use as a bioidentical hormone replacement therapy strategy. However, in clinical practice, I have seen arguable justification for pregnenolone’s therapeutic application and so, I find it relevant to acknowledge its presence amongst this hormone community space. Sometimes, a little bit of pregnenolone goes a long way!
I credit the following expression to the late Dr. James Meehan, under whom I originally trained. “Pregnenolone is the grandparent hormone”, he would say whilst on telehealth consultations providing hormonal education to his clients. “It’s also the secret weapon of public speaking”, he would advocate while picking up his own stash of bottled-up pregnenolone capsules and shaking them in front of the telehealth screen. What did he mean by this? When looking at the hormonal hierarchy, or – as I call it – the hormonal family tree, pregnenolone supersedes the sex hormones, in lineage, that we are all well aware of called estradiol, progesterone and testosterone. In fact, estradiol, progesterone and testosterone are technically the “kids” of the family and laughably so, as they get all the media attention, are “rowdy” and you’ll know when they’re misbehaving! However, before estradiol, progesterone and testosterone ever came to be, there existed a parent and grandparent hormone as progenitors – these being: pregnenolone and dehydroepiandrosterone (DHEA). Furthermore, upstream to these, cholesterol originates pregnenolone… a point we will circle back to later in this discussion.
Now, pregnenolone has unique functions independently. It preserves your color vision as you age. It helps maintain verbal fluency (hence the “public speaker weapon” commentary). It not only plays a crucial substrate role in deriving your sex hormones by providing downstream benefits of good sleep, stable moods and a robust libido but pregnenolone also supplies your daily cortisol replenishment. *Remember this tidbit – it becomes important for later.
Pregnenolone, as a derivative of cholesterol, is made in the adrenal glands, gonads, liver, brain and other organ tissues. Pregnenolone relies on healthy mitochondrial function as the chemical conversion of cholesterol into pregnenolone occurs in the cell organelle, the mitochondria.
When your endogenous (internal, authentic, original) production of pregnenolone decreases, hormonal imbalances can occur. Perimenopause, menopause and “andropause” (male menopause) classically exhibit this crime scene. Reduced levels of pregnenolone in these states can lead to worsening (or onset of) hot flashes, decreased libido, poor memory and mood and muscular weakening. However, it is not just perimenopause, menopause and andropause that prompt pregnenolone atrophy. Chronic stress, trauma and illness can also incite a pregnenolone crisis. Recall from earlier that pregnenolone replenishes your cortisol. So, under times of prolonged and/or intense fight or flight stress, your ever-so-smart and adaptable body will utilize pregnenolone as a first line survival strategy. In doing so it will take pregnenolone and progenate it, of chief priority, into cortisol thereby cutting off the sex hormone production line factory’s access to one of its chief ingredients. As a result, your adrenal glands will thrive but at the expense of your sex hormones repository. This tactical play of bodily survival is coined “The Pregnenolone Steal” and it can happen at any age and season of life.
What else contributes to pregnenolone’s possible decline? Natural aging, poor sleep, malfunctioning mitochondrial activity, dietary deficits and routine statin use are all common etiologies.
[A word on statins here: as one of the most commonly prescribed medications in the United States, a target consequence of its use will be the reduction of pregnenolone in statin-users’ bodies. I am not aware of a particular study commenting on the direct, adverse impact of statin’s reduction on pregnenolone depletion. However, I can say, from situational observations – the amount of dementia, cognitive decline and poor memory I witnessed in statin taking clients, does ring true. I believe there is credence to the circulating theory that poor neurocognitive health may be exacerbated or accelerated in statin using populations, as a function of pregnenolone decline].
Another non-evidence based but experienced-derived observation of mine has been that males tend to recognize the favorable impact of pregnenolone more than females. For my female clientele, I most typically enact a pregnenolone script when they are postmenopausal and looking to “toe-dip” themselves into bioidentical hormone therapy. Supplying the female body with the grandparent and parent hormones (pregnenolone and DHEA) to “turn the lights back on” and “water the hormonal hierarchy garden” can be a suitable strategy without women having to dive head on into estradiol, progesterone and testosterone replacement scripts. For some women, this is gentle and subtle enough for their favorable improvement. Postmenopausal women will tell me that they feel “more like themselves”, sleep better and have heightened mental clarity when using pregnenolone. However, for most postmenopausal females, pregnenolone and DHEA alone are not potent enough to mitigate all of their postmenopausal symptoms. In males though, I have more often than not witnessed a beneficial testimony with pregnenolone use. Their feedback is such that pregnenolone improved their mental capacity, eliminated brain fog and provided notable energy.
[Perhaps, as women, who tend to chronically worry and stress a little more than the male counterpart – perhaps, women burn through their pregnenolone more quickly and thus do not notice its effect as advantageously as males? Just saying!].
Again, the above personal observations I cannot claim evidence-based support. And, as mentioned in the opening, World Link Medical advanced bioidentical hormone therapy training would also not defend pregnenolone’s routine use for mitigating hormonal imbalances. However, it isn’t unreasonable to have a conversation with your provider (if they are familiarized with pregnenolone!) to consider its use in the realm of hormonal replenishment and as an option in the advanced bioidentical hormone therapy medical toolbox.
Pregnenolone, when compounded, can be delivered in oral capsules, sublingual tablets or topical cream forms. There are oral, over the counter formulas available generically at your Sprouts, Natural Grocers or other ready-to-market supplement storefronts. However, to ensure pregnenolone’s potency, purity and shelf-life, I recommend sourcing pregnenolone from a compounded, prescriptive supplier.
Ps. What level is “good enough” when it comes to checking your pregnenolone? Especially, if LabCorp et alt labs do not provide a reference range? Achieving a 50ng/dL minimum base is generally well received.