Clinical Information

Dehydroepiandrosterone (DHEA) is the principal human C-19 steroid. DHEA has very low androgenic potency but serves as the major direct or indirect precursor for most sex steroids. DHEA is secreted by the adrenal gland and production is at least partly controlled by adrenocorticotropic hormone. The bulk of DHEA is secreted as a 3-sulfoconjugate (DHEA-S). Both hormones are albumin bound, but binding of DHEA-S is much tighter. In gonads and several other tissues, most notably skin, steroid sulfatases can convert DHEA-S back to DHEA, which can then be metabolized to stronger androgens and to estrogens.

During pregnancy, DHEA-S and its 16-hydroxylated metabolites are secreted by the fetal adrenal gland in large quantities. They serve as precursors for placental production of the dominant pregnancy-related estrogen, estriol. Within weeks after birth, DHEA-S levels fall by 80% or more and remain low until the onset of adrenarche. Adrenarche is a poorly understood phenomenon peculiar to higher primates, which is characterized by a gradual rise in adrenal androgen production. It precedes puberty but is not causally linked to it. Early adrenarche is not associated with early puberty or with any reduction in final height or overt androgenization and is generally regarded as a benign condition, not needing intervention. However, girls with early adrenarche may be at increased risk of polycystic ovarian syndrome as adults, and some boys may develop early penile enlargement.

Following adrenarche, DHEA-S levels increase until the age of 20, up to maximum levels roughly comparable to that observed at birth. Levels then decline over the next 40 to 60 years to around 20% of peak levels. The clinical significance of this age-related drop is unknown and trials of DHEA-S replacement in the elderly have not produced convincing benefits. However, in young and old patients with primary adrenal failure, the addition of DHEA-S to corticosteroid replacement has been shown in some studies to improve mood, energy, and sex drive.

Elevated DHEA-S levels can cause symptoms or signs of hyperandrogenism in women. Men are usually asymptomatic, but through peripheral conversion of androgens to estrogens can occasionally experience mild estrogen excess. Most mild to moderate elevations in DHEA-S levels are idiopathic. However, pronounced elevations of DHEA-S may be indicative of androgen-producing adrenal tumors. In small children, congenital adrenal hyperplasia (CAH) due to 3 beta-hydroxysteroid deficiency is associated with excessive DHEA-S production. Lesser elevations may be observed in 21-hydroxylase deficiency (the most common form of CAH) and 11 beta-hydroxylase deficiency. By contrast, steroidogenic acute regulatory protein or 17 alpha-hydroxylase deficiencies are characterized by low DHEA-S levels.

An initial workup in adults might also include total and bioavailable testosterone (TTBS / Testosterone, Total and Bioavailable, Serum) measurements. Depending on results, this may be supplemented with measurements of sex hormone-binding globulin (SHBG /Sex Hormone-Binding Globulin [SHBG], Serum) and occasionally other androgenic steroids (eg, 17-hydroxyprogesterone).