Is it weird to have a favorite hormone?

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Or favorite neurotransmitters for that matter? Probably, but I like odd things.

A blog post by a colleague reminded me of my favorite hormones – dehydroepiandrosterone (DHEA) and its sulfated counterpart dehydroepiandrosterone sulfate (DHEAS). Actually, I’m more partial to DHEAS than DHEA. DHEA is cool, but DHEAS has an element of practicality to it that I find appealing. DHEAS is the fixer, the mom of the hormone chain; hanging out in the background until needed and then stepping in to clean things up when the teenagers below overdo themselves.

A little background; DHEA and DHEAS are adrenal androgens. They are produced in a region of the adrenal glands called the zona reticularis (the deep inner region of the gland). Recall that cortisol, the stress hormone, is produced in the adrenal cortex as well, although in the middle layer called the zona fasciculata. The outermost layer of the adrenal cortex is where aldosterone, the mineralcorticoid is produced (it regulates kidney function and sodium/potassium balance).

DHEA is a precursor hormone. That means other downstream hormones like testosterone (and other androgens) and the estrogens (estrone, estradiol and estriol) are synthesized from DHEA. Similar to other precursor hormones such as pregnenolone or progesterone, the concentrations of DHEA impact the synthesis of downstream counterparts. Its sulfated counterpart, DHEAS, can be compared to reservoir for emergency use DHEA. That is, whenever the body needs more DHEA, the sulfate is removed by enzymes and more DHEA is released into circulation.

Both DHEA and DHEAS are active in the body and in the brain. In the body, DHEA initiates puberty, is critical for pregnancy (precursor for estriol, the pregnancy estrogen), and interacts with every organ in the body, influencing immune function and especially inflammation. DHEA and DHEAS modulate what are called interleukins or cytokines – these are the cells that control inflammation. DHEA/DHEAS levels increase from birth through our 20’s and 30’s and decline thereafter. By the time we reach our 60’s-70’s, DHEA levels are virtually non-existent, leading researchers to investigate supplementation to ward off the effects of aging. The research is mixed; I would argue more so because of study design than lack of effect, but that is a topic for another conversation.

In the brain, DHEA/DHEAS modulate virtually every neurotransmitter system, but are particularly active at the GABA cells- one of my favorite neurotransmitters (dopamine is the other). GABA, short for gamma amino butyric acid, is our body’s sedative, our natural Valium. Of the steroid hormones, progesterone (and metabolites like allopregnanolone) and DHEA/DHEAS are particularly important to GABA regulation. Progesterone increases GABA, increases sedation, while DHEA and DHEAS both block GABA and decrease sedation or increase anxiety.

Think about how you feel at different points across the menstrual cycle, across pregnancy and postpartum and you’ll understand the interplay between these hormones and GABA. Around ovulation, and probably through the first week post ovulation, women typically feel pretty good. We have ever increasing doses of our Valium like substance, progesterone and just the right amount of other hormones to temper the sedation, so that we are relaxed but not totally sedated.

But then all good things must come to an end. Towards the end of the menstrual cycle, during menses itself and following childbirth—what happens? We withdraw from our sedatives. Progesterone crashes and we get cranky; really, really cranky.

But wait, there’s more. DHEA/DHEAS increases in some women and the crankiness is cranked up quite a bit. From a neurochemical standpoint, menstruation and pregnancy/postpartum are quite similar to a Valium addiction/withdrawal syndrome; ever increasing doses of progesterone, followed by rapid withdrawal, compounded by an anxiety inducing dose of DHEA/DHEAS. When folks sarcastically attribute mood changes to hormones, they are actually correct. Hormones act on the brain in much the same way as drugs do. Harness that power and we have a whole new set of drugs.

If blocking GABA by DHEAS makes us anxious and cranky, why is it my favorite hormone? Why isn’t progesterone a favorite? Progesterone, after all, is a happy, peaceful hormone. Well, progesterone is one of my favorites, precisely because it works on GABA, but there’s something about DHEAS that intrigues me. It may hold the key to so many diseases and I find this even more exciting than the sedation inducing properties of progesterone.

Lucine Woman

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  1. Thanks for your reply! Yes, I am looking into curing my mitochondria, but it’s not an easy fix and will probably take some time. The hormones are only a crutch until my mitochondrial (hopefully) will do their job again.

  2. Dear Dr. Chandler, I currently tested for pregnenolone-s and DHEA-S (female, 39) and both came back very low (preg-s was 13, ref.range 45-150; DHEA-s was 49, ref.range 100-280). There may be mitochondiral issues at the bottom of the problem.

    The pregnenolone helps me with the pain I had for years, with exhaustion and with long term insomnia.
    But: the effect reminds me or is very similar to that of benzodiatepines or pregabaline! I had horrible withdrawal symptoms from coming off pregabaline which lasted several months, so I think I may be especially sensitive to gaba induced addiction.

    I was told pregnenolone has the opposite effect and its sulfate form is binding on NMDA-receptors, opposing gaba effects. What I suspect in my case is that it readily converts into progesterone and its metabolite allopregnanolone, causing the sedation.

    I don’t want to take pregnenolone forever, as it causes severe bloating and intestinal issues, only until my levels are back to normal again. My big fear is that the pregnenolone will cause me withdrawal issues similar to those I had with pregabaline. I guess my gaba receptors don’t adjust very fast once down regulated.
    In your article you wrote that DEHA-S opposes the the gaba effects. So I ask myself if it would be wise to counterbalance the allopregnanolone effects with DHEA?

    Any suggestions/experiences about the “withdrawal”-part? Did you ever hear someone has problems coming off pregnenolone/progesterine? Thank you so much!

    1. Like anything taken for an extended period of time, the body will adapt to it and make changes, whether it is a drug or hormone. When you come off of these substances, it is important to reduce your usage very, very gradually over an extended period of time to allow your body to re-adapt. I would imagine coming off of pregnenolone rapidly would be similar to the hormone crash many women get postpartum. As far as counterbalancing, I wouldn’t suggest it. Just go very slowly. I would suggest, however, that you looking into potential mitochondrial issues, the nutrients that feed and support mitochondria so that the mitochondria can produce the hormones versus having to take them.

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