DHEA and DHEA-S

Prohormone, mild androgen, and other effects.

Both DHEA (dehydroepiandrosterone) and DHEA-S (dehydroepiandrosterone sulfate) are generally misunderstood, despite being one of the most abundant hormones in humans. Both are considered prohormones (or precursor hormones) that are converted downstream to androgens (testosterone, DHT) and estrogens (estrone, estradiol), but they also have some important direct hormonal effects as well.

Similar to testosterone, it is known that DHEA and DHEA-S levels can decline with aging, but it can decrease due to chronic stress and other factors we’ll discuss.

DHEA vs DHEA-S:

First, let’s clear up the difference between DHEA and DHEA-S and talk about where these are made.

These hormones are primarily made in the adrenal glands, although they are made in lesser extents in the gonads (testes and ovaries), brain, liver, and skin.

Recall from our discussion of pregnenolone that it can be converted either to progesterone or DHEA, either of which can be converted to androstenedione (similar to DHEA, this is primarily a prohormone, but has some weak androgenic effects as well).

Once DHEA is formed, it can be converted to DHEA-S through a sulfation reaction, which involves the addition of a sulfate group to the DHEA molecule by the enzyme sulfotransferase 2A1 (SULT2A1). Again, the majority of this reaction occurs in the adrenals, but also occurs in other tissues as well. When you take supplemental DHEA, the sulfation reaction occurs in the intestines and liver.

Summary of differences between DHEA and DHEA-S:

• Our levels of DHEA-S are typically 250-300 times the amount of DHEA in circulation. (Most labs report DHEA levels in ng/dL and DHEA-S levels in mcg/dL).