DHEA and Pregnénolone: "Doctors Haven't Reinvented the Wheel"
Pregnenolone and DHEA: When Doctors Rediscover… the Wheel!
For some time now, there has been a surge in discussion about DHEA and pregnenolone, as if the medical community had suddenly discovered that these hormones exist, that they play a role in hormonal balance, and that their levels can decline with age.
Welcome to the wonderful world of steroidogenesis! (the production of steroid hormones such as cholesterol and vitamin D3, as well as all reproductive hormones—including progesterone, estrogen, and testosterone—and DHEA and pregnenolone)
You can almost hear them saying, “Look! Pregnenolone! DHEA! It’s amazing!”
Yes… wonderful. But there’s one small detail that we sometimes forget: hormones don’t just fall from the sky.
Above all, administering a hormone does not necessarily mean that the underlying cause of the body’s inability to produce enough of it has been corrected.
That is precisely where the mitochondrion comes into play.
Pregnenolone: The Starting Point of an Entire Hormonal Cascade
Pregnenolone is produced from cholesterol. This initial conversion takes place in the mitochondria and involves, in particular, the enzyme CYP11A1, also known as P450scc. The transfer of cholesterol into the mitochondria is an essential step in steroidogenesis.
In other words:
cholesterol → pregnenolone → various steroid hormones
From pregnenolone, the body can produce, depending on the tissues and enzymatic pathways involved, progesterone, DHEA, cortisol, androgens, and estrogens, among other substances.
The mitochondrion, therefore, is not simply a small powerhouse located somewhere inside the cell.
It plays a direct role in the production of steroid hormones.
And that's where things get a lot more interesting.
"Are you low on pregnenolone? Let's give you some pregnenolone!"
It's a bit like noticing that a car has stopped moving because its engine is having trouble and responding:
"It doesn't have enough power? Let's put more gas in it!"
This might get the car running temporarily.
But if the engine overheats, the oil is degraded, and parts are damaged, the underlying problem still hasn't been resolved.
When it comes to steroidogenesis, the reasoning must be much more nuanced.
When pregnenolone or DHEA levels are low, the obvious question is:
Why is this production declining?
Is it solely because the organism lacks a substrate?
Is this related to age?
Going through menopause?
Is it ovarian or adrenal insufficiency?
An enzymatic disturbance?
Chronic physiological stress?
Persistent inflammation?
Or to impaired mitochondrial function?
Because if the mitochondrial machinery isn't working properly, adding the end product or an intermediate compound doesn't necessarily solve the original problem.
Mitochondria: At the Heart of the Problem
The production of steroid hormones depends on an extremely complex cellular mechanism.
Cholesterol must be transported to the mitochondria and then made available to the CYP11A1 enzyme so that it can be converted into pregnenolone. The StAR protein, in particular, plays an essential role in the transport of cholesterol to the mitochondria.
This means that the ability to produce hormones also depends on the cell's ability to properly operate this machinery.
And a mitochondrion can be put under a great deal of stress by many factors.
Factors that can impair mitochondrial function include, among others:
- an excess of certain heavy metals;
- significant oxidative stress;
- chronic inflammation;
- persistent immune dysfunction;
- changes in energy metabolism;
- certain environmental hazards;
- metabolic disorders;
- and, in certain contexts, persistent or recurrent infections.
We can also consider the metabolic consequences of a mitochondrion that functions less efficiently.
When mitochondria can no longer properly produce the energy needed by the cell, metabolism can gradually become disrupted. This may be accompanied by a decrease in metabolic flexibility, less efficient use of energy substrates, and reduced insulin sensitivity.
Over time, this condition can lead to insulin resistance, increased energy storage, and, in some people, weight gain or being overweight (regardless of the quality or quantity of the food consumed).
This creates a real vicious cycle:
mitochondrial dysfunction → impaired energy utilization → decreased insulin sensitivity → insulin resistance → increased nutrient storage → weight gain → metabolic inflammation → worsening of oxidative stress and mitochondrial function.
And this cycle can, of course, be perpetuated by other factors: diet, a sedentary lifestyle, sleep disorders, chronic stress, inflammation, persistent infections, etc.
This is where I use the term“cold infections ”: persistent infections or infectious agents, sometimes with few symptoms, that can maintain chronic immune stimulation.
What if inflammation were also caused by these persistent infections?
When we talk about chronic inflammation, we often immediately look for:
diet,
stress,
the microbiome,
toxins,
excess weight,
insulin resistance…
But we also need to ask ourselves a question:
What if part of the immune system were constantly stimulated by persistent infectious agents?
In the terminology I use in my practice, I refer to these as“cold infections.”
Depending on the situation and the parties involved, this concept may include, among other things:
- certain persistent Borrelia infections;
- tick-borne co-infections such as Bartonella or Babesia;
- certain persistent or reactivated viruses, including EBV;
- CMV in certain contexts;
- certain intracellular bacterial agents;
- certain persistent gastrointestinal infections;
- certain fungal infections or fungal overgrowths;
- certain persistent parasitic infections.
⚠️ However, it is important to be precise: the presence of an infectious agent or antibodies does not automatically mean that an active infection is present. Diagnosis and interpretation must be based on appropriate clinical and laboratory data.
The interesting idea lies elsewhere:
Persistent immune stimulation may contribute to maintaining an inflammatory and oxidative environment.
And when a cell is exposed to this environment over a long period of time, the mitochondria may end up paying the price.
Immunooxidation: The Vicious Cycle
We can then imagine a circle:
persistent agent → immune stimulation → inflammation → oxidative stress → impaired mitochondrial function → decreased energy and metabolic capacity → disruption of certain cellular functions.
And the more a mitochondrion is under stress, the more vulnerable it can become.
This is particularly interesting when discussing steroid hormones, because mitochondria play a direct role in the early stages of their synthesis.
So yes, pregnenolone can be administered.
Yes, DHEA can be administered.
But if we don't identify the underlying cause that prevents the body from functioning properly, we risk treating only the symptom.
And what about cholesterol?
Here's another particularly interesting point.
We sometimes hear:
"Your cholesterol is high: you need to lower it."
But cholesterol isn't just a waste product that the body is desperately trying to get rid of.
It is also an essential precursor to steroid hormones.
Cholesterol is used, in particular, to produce pregnenolone, which serves as a starting point for many steroidogenesis pathways.
And that's why the question becomes much more interesting:
Why does cholesterol rise?
In some women, particularly around the time of menopause, significant changes in the lipid profile are indeed observed, including an increase in total cholesterol and LDL cholesterol. The decline in estrogen and the metabolic changes associated with the menopausal transition contribute to this change.
But be careful not to tell a story that's too simplistic.
It is not necessarily:
"The ovaries stop functioning → cholesterol levels rise simply because the body wants to produce more pregnenolone."
Physiology is much more complex.
Menopause alters, among other things, hepatic lipid metabolism, fat distribution, and the lipoprotein profile.
However, the link between cholesterol, mitochondria, and steroidogenesis clearly warrants further understanding before prescribing statins or even attempting to lower cholesterol.
So why does cholesterol levels rise?
Because cholesterol has many functions.
He is involved in:
- cell membranes;
- cell signaling;
- the synthesis of steroid hormones;
- the production of bile acids;
- various metabolic processes.
And when ovarian function declines—particularly during menopause— the ovaries' production of estrogen drops sharply.
The lipid profile also changes as a result.
But we must also ask whether, in some people, overall hormonal and metabolic production capacity is limited by the quality of mitochondrial function.
This is where the reasoning becomes much more interesting than:
"Low hormone levels = hormone replacement."
DHEA and pregnenolone aren't batteries that can be recharged indefinitely
That's the key point.
If the body has a reduced ability to produce certain hormones properly, temporarily administering pregnenolone or DHEA can alter circulating levels.
But that doesn't mean it has been restored:
- mitochondrial function;
- managing oxidative stress;
- inflammatory balance;
- energy metabolism;
- the capacity for steroidogenesis;
- or the reason for this decrease.
It is possible to maintain a track without having repaired the plant.
And that is precisely why, from a functional perspective, the question should not only be:
"Which hormone is missing?"
but also:
"Why is this hormone lacking?"
The real question: Why do mitochondria get tired?
That is why, when DHEA or pregnenolone levels are low, it is important to consider the overall health picture.
Heavy metals?
Oxidative stress?
Chronic inflammation?
Immune dysfunction?
Persistent infections?
Metabolic disorders?
Insulin resistance?
Weight gain or being overweight?
Decreased insulin sensitivity?
Mitochondrial dysfunction?
And most importantly:
Is there chronic immune stimulation caused by a persistent infection or another inflammatory factor?
Because you can always try to fill up the tank.
But if the mitochondrial engine is struggling, maybe it's time to take a look at the engine.
And that's where pregnenolone and DHEA really come into their own: not simply as substitutes, but as markers and key players in a hormonal system whose entire chain must be understood.
So perhaps medicine hasn't exactly reinvented the wheel.
She simply took another look at an old biochemical fact:
Cholesterol isn't just cholesterol, pregnenolone isn't just a hormone, DHEA isn't just a supplement… and behind it all, there's a mitochondrion working—often only part-time—which consequently leads to this drop in hormone levels.
And before asking her to produce more DHEA and pregnenolone or to supplement these hormones, it might be wise to consider her current condition and examine how her body functions.
