Rather than hyped features of DHEA as a supplement, I focus on its neurosteroid effects and explain compelling reasons to get it checked and optimize it naturally.

This story does not include health advice. It is for information, inspiration, and awareness purposes.

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DHEA is a hormone of considerable importance, extensively researched yet mired in controversy due to its potential for misuse. Too much or too little of DHEA can be problematic. Before unfolding its intricacies with nuances based on my intense research, I’d like to highlight its indirect role as a neurosteroid, a facet often overlooked but significant, particularly concerning cognitive function, which interests me.

Although DHEA is adrenal androgen, it is a precursor of the neurosteroid androsterone. As documented in this paper:

“As DHEA acts directly as a neurosteroid and serves as an indirect precursor of several neurosteroid hormones, it is possible that alterations in neurosteroid levels within the CNS could contribute to the antidepressant effects of DHEA described in preliminary reports.”

A neurosteroid is a steroid hormone synthesized within the central nervous system by glial cells and neurons, including the brain and spinal cord. Neurosteroids exert neuromodulatory effects on the brain. Neuromodulatory effects mean the ability of specific molecules or signals to regulate or modify the activity of neurons in the nervous system.

As documented in this paper,:

“Based on structural features, neurosteroids can be classified as pregnane neurosteroids, like allopregnanolone and THDOC, androstane neurosteroids, like androstanediol and etiocholanone, and sulfated neurosteroids, like pregnenolone sulfate and DHEAS.”

First, let me clarify the difference between DHEA and DHEA-S. They are two forms of the same hormone, but they serve different purposes in the body. DHEA is the parent hormone synthesized by the adrenal glands, and it serves as a precursor to other hormones like testosterone and estrogen.

On the other hand, DHEA-S is a sulfated form of DHEA that circulates in the bloodstream at much higher levels than DHEA. DHEA-S is a storage form of DHEA, and it is less active biologically than DHEA. However, DHEA-S can be converted back into DHEA as needed by the body to regulate hormone levels and perform various physiological functions.

DHEA and its sulfate ester DHEA-S play roles in neuroprotection, mood regulation, and cognitive function. They modulate neurotransmitter systems, including GABA, glutamate, and dopamine, regulating mood, stress response, and cognitive function in the brain.

So, three essential neuro-functions of DHEA/DHEA-S as a neurosteroid are modulating neurotransmission, neural excitability, and neuroprotection. They can interact with neurotransmitter receptors, like GABA and NMD receptors, influencing neuronal activity and synaptic transmission.

In simple terms, synaptic transmission refers to the process by which nerve cells communicate with each other through the transmission of electrical or chemical signals across synapses, enabling the transfer of information within the nervous system.

As documented in Frontiers, neurosteroids have been implicated in regulating mood, anxiety, stress response, and cognitive functions like memory and attention. They have been investigated for their potential therapeutic effects in neurological and psychiatric disorders, including depression, anxiety disorders, epilepsy, and neurodegenerative diseases.

Neurosteroids represent molecules that contribute to the complex regulation of brain function and may hold promise for developing novel treatments for neurological and psychiatric conditions. Steroid hormones and neurosteroids are believed to play a vital role in the sex-specific forms of epilepsies and gender-related seizure susceptibility.

Research suggests they play pivotal roles in neurological and psychiatric conditions like epilepsy, anxiety, and depression, offering potential therapeutic avenues. Their pharmacological effects mainly stem from their ability to enhance GABA-A receptors, highlighting their significance in brain function and mental health.

After this brief background to neurosteroids, I want to give an overview of DHEA more specifically and why this hormone matters for our physical and mental health.

Quick Insights for Nuances of DHEA from the Literature

The discovery of the chemical structure of important DHEA metabolites earned Adolf Butenandt and Leopold Ruzicka the Nobel Prize in 1939.

Much attention has been paid to DHEA and DHEA-sulfate, which represent the significant androgens secreted by the adrenal glands that have progressed in the last few decades. DHEA helps produce other hormones, including testosterone and estrogen.

This 2022 paper critically reviews DHEA’s biological effects, mechanism of action, and therapeutic potential, especially in CNS disorders. In summary, DHEA is a vital steroid hormone primarily produced in the adrenal cortex, the outer portion of the adrenal glands located on top of the kidneys.

More specifically, as documented in this paper, “DHEA is produced by the adrenal gland in humans and is taken up by several tissues, including the brain, liver, kidney, and gonads, where it is metabolized to 5-androstene-3β,17β-diol, 4-androstene-3,17-dione, testosterone, estrogen, and other biologically active steroids, depending on the tissue.”

As documented in this paper, various functions, including metabolic, immune, and cognitive effects, have been attributed to this steroid. Since the levels of DHEA correlate with general good health, and aging is associated with a decline in the secretion of this steroid, a growing interest in replacing DHEA in elderly people has developed.

Some support for DHEA as a therapeutic compound has been demonstrated for postmenopausal women, in vitro fertilization, and several autoimmune disorders, and adverse health effects, such as acne, embryo virilization during pregnancy, and possible endocrine-dependent cancers.

As reported in this paper: “Low levels of DHEA have been associated with mental health disorders like schizophrenia and early onset dementia. DHEA treatment has shown promise in improving symptoms of schizophrenia and depression, although the role of abnormal brain DHEA synthesis in these conditions is debated. DHEA administration may also reduce inflammation in the brain by lowering pro-inflammatory cytokines and potentially protecting against brain injury.”

Over a decade, this comprehensive review paper informed that while initially hailed as an ‘anti-aging’ hormone based on animal studies, recent human trials have validated some of these claims.

The review pointed out that in the elderly, DHEA improves immune function, muscle strength, bone density, and psychological well-being while reducing body fat and skin aging. In conditions like adrenal insufficiency and systemic lupus erythematosus, DHEA shows promise in restoring hormone levels and improving symptoms.

The review paper also mentioned that it exhibits cardiovascular and anti-inflammatory benefits, and it may help in conditions like asthma and allergies. However, inconsistent study results stem from various factors, including differences in dosing, metabolism, and reliance on animal models.

It concludes that despite this, emerging evidence suggests DHEA could be a valuable treatment for specific human diseases, pending further large-scale clinical trials for precise dosing and indications.

Another 2014 review mentioned that a neuroactive hormone, DHEA, along with other hormones and transmitters, significantly affects some aspects of mood and modifies some features of human emotions and behavior.

The review informed that its medical administration can increase feelings of well-being and is useful in alleviating atypical depressive disorders. It has neuroprotective and anti-glucocorticoid activity and modifies immune reactions, and some authors have also reported its vital role in degenerative brain diseases.

Is supplementation of DHEA Necessary?

DHEA affects our organs and systems, showing potential as a pharmacological agent as it has neuroprotective, cognitive, and mood-related benefits. Clinical studies only support its use in hypoadrenalism, depression, and cognitive disorders. However, misuse of DHEA as a dietary supplement among healthy people has risen in the 1980s and 1990s

Regarding its supplementation, this 2008 study (Double-blind, randomized, controlled clinical trial) confirmed that “DHEA supplementation has no benefit on cognitive performance or well-being in healthy older adults, and it should not be recommended for that purpose in the general population.”

As updated by USADA in December 2023, “While DHEA is allowed in the U.S. in both medications and over-the-counter supplements, it is considered a prohibited anabolic agent in sport. Athletes should be mindful that DHEA has limited medical purposes, and despite being allowed in dietary supplements, there is no evidence that DHEA supplements are a safe or effective treatment for any disease.”

WebMD informed that “DHEA is banned by the National Collegiate Athletic Association (NCAA), the International Olympic Committee, and the World Anti-Doping Agency (WADA).”

DHEA levels fluctuate throughout life, with higher levels linked to longevity. Conditions like adrenal insufficiency, severe diseases, stress, and anorexia can decrease DHEA levels. Recent research highlights its importance in the central nervous system (CNS), although its specific receptor remains unidentified.

Like in the USA, DHEA supplements are sold over the counter in some countries. But some others ban it.

Why is checking DHEA levels important?

Checking DHEA hormone levels can be helpful for people of all ages and genders, as it profoundly influences various aspects of health and well-being.

In men, the test for DHEA-S is typically performed in conjunction with assessments for testosterone and other male hormones to evaluate the adrenal glands’ functionality.

This evaluation might distinguish conditions originating from the adrenal glands, testicles, or ovaries, and it facilitates the diagnosis of adrenal gland tumors and adrenal cancers—furthermore, the test aids in identifying congenital adrenal hyperplasia and adrenal gland enlargement in adults.

Additionally, DHEA-S levels are analyzed alongside other hormones to investigate virilization in young girls and early puberty in young boys.

Similarly, in women, DHEA-S levels are assessed alongside other hormonal markers to diagnose various conditions, including polycystic ovary syndrome, infertility, amenorrhea, and hirsutism.

A comprehensive evaluation allows healthcare providers to gain insights into the hormonal balance and potential underlying issues affecting women’s reproductive health and overall well-being.

Therefore, the measurement of DHEA-S levels plays a vital role in diagnosing and managing hormonal imbalances and related health concerns in men, women, and children throughout their lifespan.

DHEA, a precursor hormone, is pivotal for testosterone and estrogen production and is vital for reproductive health in both genders. It offers insights into adrenal gland function, which is crucial for stress management and energy regulation.

Imbalances signal adrenal fatigue, leading to fatigue and mood changes. Adequate DHEA’s natural anti-aging properties can enhance vitality, immune function, cognitive health, and bone density, which are crucial as we age.

For women in menopause, monitoring DHEA levels aids in managing symptoms like hot flashes and mood swings.

According to this verified testing resource, excess DHEA-S might go unnoticed in adult men. Trigger early puberty in young boys. Result in amenorrhea and virilization in girls and women, like hirsutism. And cause ambiguous external genitalia in female babies at birth. Here’s guidance from testing.com:

For women experiencing symptoms like irregular periods, infertility, or signs of developing masculine features, a DHEA-S test might be necessary. These features include a deeper voice, excessive body hair (hirsutism), male pattern baldness, increased muscle mass, acne, Adam’s apple enlargement, or reduced breast size.

In some cases, it is also ordered when there’s uncertainty about genitalia appearance in girls. In young boys, a DHEA-S test may be needed if signs of early puberty appear, such as a deepening voice, early growth of pubic hair, muscle development, or enlargement of the penis before the usual age of puberty.

Like other hormones, DHEA levels can be tested via blood, as this Mediplus article explains.

How to Optimize DHEA Levels?

You may ask, if health authorities do not recommend supplementation, how can we optimize this vital hormone?

Like all other hormones, optimizing DHEA levels can be approached by balancing fundamental lifestyle aspects like a nutritious diet, adequate sleep, and regular exercise.

The key point for these lifestyle factors is managing stress, as our adrenal function significantly affects the balance of DHEA. Maintaining a healthy weight is also an excellent contributor to its optimization.

Maintaining a healthy weight can indirectly contribute to optimizing DHEA levels by promoting hormonal balance, metabolic health, inflammation reduction, and stress management.

Two indirect risk factors for its decline are alcohol and caffeine. Excessive alcohol consumption and high caffeine intake can disrupt hormonal balance. Although caffeine does not directly affect DHEA, it can negatively impact adrenal function and decrease insulin sensitivity. Thus, limiting alcohol and caffeine intake might support overall hormone health, including DHEA.

As documented in this paper, “Chronic consumption of a large amount of alcohol disrupts the communication between the nervous, endocrine and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiological and behavioral levels.”

In some medical conditions, supplementation with DHEA may be recommended under the guidance of a healthcare professional. However, supplementation should only be considered after a thorough evaluation of hormone levels and consultation with an endocrinologist.

Conclusions and Takeaways

DHEA, a hormone affecting the nervous system, works with other hormones and brain chemicals to influence our mood, emotions, and behavior. DHEA can protect the brain cells and reduce the effects of stress hormones like cortisol. It also can impact the immune system and may play a role in diseases that affect the brain as they progress.

From my experience and discussions with endocrinologists, DHEA-S levels aren’t typically checked as part of routine testing by family doctors. However, family doctors or endocrinologists may order a DHEA-S test and other hormone tests if there is suspicion of excess or insufficient androgens or to assess adrenal gland function.

The function of the adrenal glands is crucial for several reasons. Firstly, they produce hormones that regulate metabolism, immune function, blood pressure, and stress response. Without proper adrenal function, hormone levels can become imbalanced, leading to health issues like fatigue, weight fluctuations, immune system dysfunction, and mood disorders.

Additionally, adrenal glands are vital in managing stress by releasing cortisol, the primary stress hormone. Chronic stress can tax the adrenal glands, leading to adrenal fatigue or dysfunction, which further exacerbates health problems. Therefore, maintaining adrenal gland health is essential for overall well-being and resilience to stressors.

Based on our current knowledge, DHEA supplementation is generally unnecessary for healthy people, but it can be prescribed to treat certain health conditions. Therefore, its use should be supervised by qualified healthcare professionals to ensure appropriate dosage and safety.

We must have a healthy lifestyle to optimize DHEA levels like other hormones. This includes consuming nutritious whole foods, managing stress through regular exercise, adequate rest, quality sleep, leisure activities, and avoiding harmful substances.

Thank you for reading my perspectives. I wish you a healthy and happy life.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.