pregnenalone, DHEA and cortisol

[mhr4]

Hey Group,

Does pregnenalone and/or DHEA impact cortisol levels? I ask because my doc recently prescribed these for me and when I took them today, it really did a number on me. I had to go to bed and I feel very brain fogged. I suffer from adrenal fatigue and I am currently taking 25mg of HC. Thanks for any info.

mhr4

[DrMariano2]

@mhr4 2922 wrote:

Hey Group,

Does pregnenalone and/or DHEA impact cortisol levels? I ask because my doc recently prescribed these for me and when I took them today, it really did a number on me. I had to go to bed and I feel very brain fogged. I suffer from adrenal fatigue and I am currently taking 25mg of HC. Thanks for any info.

mhr4

I don’t use the term adrenal fatigue. One can call it hypothalamic-pituitary-adrenal axis dysregulation – which is the psychiatric term for the condition. One short-hand term I like is adrenal dysregulation.

Pregnenolone and DHEA can be given when adding Hydrocortisone in an adrenal signaling support treatment. This helps reduce the risk of side effects from giving hydrocortisone alone – which is an incomplete treatment since it also reduces one’s own adrenal output. For example, the addition of an androgen like DHEA helps reduce the risk for bone density loss and insulin resistance.

However, even the addition of Pregnenolone and DHEA can still be incomplete. For example, progesterone signaling is suppressed by the addition of Hydrocortisone. Progesterone is calming and mood stabilizing to the brain, among its many actions. Its loss may result in an increase in anxiety/stress signaling. Testosterone and estrogen production is suppressed by hydrocortisone. These can be particularly worrisome to women since it can result in impaired cognition and mood worsening.

Pregnenolone and DHEA are also precursors for many estrogens. The increase in estrogen signaling, if in excess in susceptible persons (since not all persons convert pregnenolone and DHEA to excess estrogens), can then significantly reduce thyroid signaling by stimulating an increase in thyroid binding globulin. This can then increase stress signaling and inflammatory cytokine signaling. The estrogens, themselves, in excess, can directly lead to an increase in inflammatory cytokine signaling. The sum of these signaling changes and the downstream cascade of signaling changes includes changes in brain structure (including loss of brain mass in certain areas, hypersensitivity of certain sensory neurons such as pain center neurons, etc.), and behavioral changes such as fatigue, loss of motivatino for activities, impaired concentration, impaired memory, social isolation, excessive non-restorative sleep, aches and pains, a variable change in appetite (up or down), etc. The signaling changes can further dysregulate adrenal function, lowering cortisol and other signaling in response to stress.

These problems do not occur with everyone. In general, adding pregnenolone and DHEA to a person deficient in these signals has positive effects. A small subset of persons may experience the negative effects. And thus one has to be alert to the possible undesired downstream signaling changes that may occur by adding a signal. This can result in the opposite of one’s intended effect.

[mhr4]

Thanks for the response Dr. M. I hope you don’t mind, I just have one more question. Do you know why some people get very irritable and anxious after taking pregnenalon?

Thanks.

[DrMariano2]

@mhr4 2936 wrote:

Thanks for the response Dr. M. I hope you don’t mind, I just have one more question. Do you know why some people get very irritable and anxious after taking pregnenalon?

Anxiety and irritability are emotions triggered by excessive norepinephrine signaling.
Norepinephrine is the primary distress signal, among its many functions.

Pregnenolone is the precursor for all the cholesterol-based hormones.

Some of them, such as the estrogens, can lead to signaling cascades which increase norepinephrine signaling.

Some of them, such as testosterone and progesterone, can lead to signaling cascades that decrease norepinephrine signaling.

Depending on the sum of the the signaling cascades – and everyone is different – though generally the changes are positive – one can get anxious and irritable rather than calm on pregnenolone.

[mhr4]

Great! Thanks again for the response.

Cheers.

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