Differences Between DHEA and DHEA-S

A 45-year-old patient comes in with fatigue, low mood, brain fog, and decreased libido. Even though cortisol levels look normal, the symptoms continue. 

In situations like this, understanding the difference between DHEA and DHEA-S can help clinicians get a clearer picture of adrenal function, androgen balance, and long-term hormone health. 

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) are related adrenal hormones, but they act differently in the body and are interpreted differently in tests. 

DHEA is a short-acting, time-of-day- and stress-dependent hormone, while DHEA-S is a more stable, stored form that reflects long-term adrenal and HPA-axis activity. 

DHEA-S is found in the blood at much higher levels than DHEA and persists longer, making it a better marker of long-term hormone patterns rather than short-term stress. 

Both DHEA and DHEA-S decrease with age, but at different rates and with different effects. 

Studies show that DHEA-S levels drop by about 80–90% between ages 25 and 75, making it a strong marker of aging.  

Low DHEA-S is linked to lower bone density, weaker immune function, and memory problems. High DHEA-S may suggest conditions like PCOS or adrenal hyperplasia, depending on the situation and symptoms. 

Understanding what sets DHEA apart from DHEA-S gives you the insight you need to pick the right test for your patient, whether you’re trying to determine whether stress is playing a role, assess how their adrenals have been functioning over time, or get to the bottom of androgen-related concerns. 

Let’s explore how each marker behaves in the body, when it makes sense to order them, and how to interpret the findings within the broader hormone and metabolic picture. 

Looking to interpret adrenal activity over time? The Comprehensive Hormone Panel includes both DHEA and DHEA-S to assess acute stress response and long-term adrenal output. 

Key Takeaways 

• DHEA is the more dynamic marker. It shifts with circadian rhythm and acute stressors, so timing and context matter.
• DHEA-S is more stable and circulates at much higher concentrations (often cited as 100–500× higher than DHEA), making it better for long-term pattern tracking.
• If the clinical question is hyperandrogenism source (e.g., PCOS or androgen-secreting tumor workup), DHEA can be a more targeted signal. For trend and resilience, DHEA-S is often preferred.
• Don’t interpret adrenal markers in isolation. DHEA/DHEA-S are most useful alongside cortisol rhythm and other adrenal precursors.
• DHEA output declines with age (after early adulthood), so reference ranges and interpretations should be age-aware. 

Table of Contents 

• What DHEA Actually Does in the Body
• Understanding DHEA-S and Why It’s Important
• DHEA vs. DHEA-S: Key Differences
• When and Why to Test Each
• Why DHEA and DHEA-S Should Be Interpreted Together 

What DHEA Actually Does in the Body

DHEA (dehydroepiandrosterone) is a steroid hormone produced primarily by the adrenal glands, with some production in the gonads and brain. 

DHEA functions as a precursor hormone. It supplies substrate for downstream sex steroids, including testosterone and estradiol, through tissue-specific enzymatic pathways. 

DHEA itself is a relatively weak androgen. Its value lies in its ability to be converted into more active hormones in response to local needs. 

Enzymes like 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase convert DHEA into androstenedione, testosterone, and estradiol. 

This local conversion (intracrine activity) helps explain why checking DHEA can be useful even when someone’s circulating sex hormones look normal on paper. 

You’ll often see DHEA come up when evaluating energy, libido, immune function, and how well someone recovers from stress, usually as part of a more comprehensive hormone workup. 

DHEA production follows a predictable arc throughout life. It peaks in your 20s and then declines steadily, about 2% per year after age 30. 

DHEA also has a short half-life in the bloodstream, which means it’s more responsive to current conditions: stress, skipping meals, illness, or even a tough workout. That’s why a single DHEA test can vary widely depending on timing. 

DHEA’s Role in the Brain

DHEA isn’t just a hormone. It’s also made directly in the brain, where it acts as what’s called a neurosteroid. Research shows that DHEA and its breakdown products can influence neurotransmitter systems involved in mood, the stress response, and cognitive function. 

This is part of why it makes sense to check DHEA when patients come in with complaints like low mood, feeling worn down by stress, or brain fog, especially in older adults or people who’ve been under chronic stress. 

DHEA and Metabolism, Immunity

DHEA also has a hand in metabolism and immune function. 

Research suggests it may affect insulin sensitivity and help regulate inflammation, including the balance of signaling molecules like cytokines. These connections are nuanced and depend heavily on context, which is why DHEA works best when viewed alongside other adrenal and metabolic markers rather than in isolation. 

Understanding DHEA-S and Why It’s Important

DHEA-S (DHEA sulfate) is the storage version of DHEA, formed when a sulfate group gets attached to DHEA in the adrenal glands and liver. 

That sulfate group changes how DHEA-S behaves once it’s in the bloodstream: it binds more tightly to carrier proteins, circulates at much higher levels, sometimes 100 to 500 times higher than DHEA, and sticks around longer thanks to a longer half-life. 

DHEA-S acts as a reservoir hormone. Tissues can reconvert DHEA-S back into active DHEA as needed, which is part of why DHEA-S is widely used as a marker of long-term adrenal output and HPA-axis activity, rather than moment-to-moment stress fluctuations. 

Because adrenal hormones don’t work in isolation, DHEA and DHEA-S tell you the most when you look at them alongside other adrenal markers. As Dr. Mitch Ghen, integrative medicine physician and educator with 33 years of experience, shared in our Access Live: 

“You should always look at the other adrenal hormones, including DHEA and pregnenolone, because they all come from the adrenal cortex and influence one another.” — Dr. Mitch Ghen 

DHEA gives you a snapshot of what’s happening right now, more dynamic, short-term shifts, while DHEA-S reflects the bigger picture of adrenal output over time. When you pair them with related hormones, you get a more accurate read on what’s actually going on. 

DHEA vs. DHEA-S: Key Differences 

DHEA and DHEA-S are closely related biochemically, but they play very different roles when you’re assessing adrenal and endocrine function. Knowing how they differ helps you pick the right test depending on whether you’re investigating acute stress responses, hyperandrogenic conditions, or overall adrenal resilience over time. 

As Dr. Mitch Ghen explains, “DHEA and DHEA-S are found in two forms in the human body. DHEA is unconjugated and released in bursts as your body needs it, while DHEA-S, the sulfated form, is about 98 percent of what’s in circulation and far more stable. The half-life of DHEA-S is roughly 10 hours, compared to only 15 to 20 minutes for DHEA.” 

He continues. “If you’re trying to pinpoint the source of a hyperandrogenic state, something like PCOS or an androgen-secreting tumor, DHEA is your test. But for wellness or functional workups, DHEA-S offers the most reliable picture of adrenal reserve over time.” 

DHEA shifts throughout the day with the circadian rhythm and reacts to immediate stressors. DHEA-S provides a window into chronic metabolic and endocrine health, capturing sustained adrenal production rather than momentary fluctuations. 

This distinction is supported by research showing that DHEA fluctuates with circadian rhythms and acute stress. DHEA-S serves as a chronic biomarker of metabolic and endocrine health, reflecting sustained adrenal production rather than momentary changes. 

When and Why to Test Each

When you need to assess what’s happening with the adrenals in real time, DHEA is the better choice. Its short half-life means levels can change rapidly in response to immediate factors like stress, a workout, skipped meals, being under the weather, or a bad night's sleep. 

For a longer-term view of adrenal function and resilience, DHEA-S is more useful. It remains stable in circulation and captures ongoing adrenal and HPA-axis activity, making it well-suited for monitoring patterns that develop over weeks to months. 

Adrenal hormones should be considered part of a broader adrenal profile. Looking at just one marker without considering the others can leave you with an incomplete picture.

Why DHEA and DHEA-S Should Be Interpreted Together

Grasping this difference is what keeps a “normal cortisol” from turning into a clinical dead end. It’s also what helps you connect the dots between fatigue, mood shifts, libido issues, and hyperandrogenic patterns. 

Here’s the other piece: adrenal hormones don’t work alone. As Dr. Mitch Ghen puts it, “You should always look at the other adrenal hormones, including DHEA and pregnenolone, because they all come from the adrenal cortex and influence one another.” 

Pairing DHEA and DHEA-S with cortisol rhythm, thyroid markers, and precursor hormones gives you context that a single value can’t. 

So which test should you order? It depends on what you’re trying to find out. 

DHEA tells you about current adrenal activity and what’s happening today. 

DHEA-S shows you the trend line and how the adrenals have been performing over weeks or months. 

If you want the complete picture, order both as part of a comprehensive hormone panel. That way, you’ll have enough information to interpret the results correctly and figure out your next move. 

Want the adrenal story, not just a single plot point? The Comprehensive Hormone Panel includes both DHEA and DHEA-S, so you can separate “today’s stress spike” from the longer-term trend—and interpret what to do next with way more confidence. 

Disclaimer: Content on the Access Medical Labs blog is for informational purposes only and reflects the views of individual contributors, not necessarily those of Access Medical Labs. We do not endorse specific treatments, products, or protocols. This content is not a substitute for professional medical advice. Always consult a qualified healthcare provider regarding any medical concerns.

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