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 (ACTH). The bulk of DHEA is secreted as a 3-sulfoconjugate dehydroepiandrosterone sulfate (DHEAS). Both hormones are albumin bound, but DHEAS binding is much tighter. As a result, circulating concentrations of DHEAS are much higher (>100-fold) compared to DHEA. In most clinical situations, DHEA and DHEAS results can be used interchangeably. In gonads and several other tissues, most notably skin, steroid sulfatases can convert DHEAS back to DHEA, which can then be metabolized to stronger androgens and to estrogens.

During pregnancy, DHEA/DHEAS and their 16-hydroxylated metabolites are secreted by the fetal adrenal gland in large quantities. They serve as precursors for placental production of the dominant pregnancy estrogen, estriol. Within weeks after birth, DHEA/DHEAS levels fall by 80% or more and remain low until the onset of adrenarche at age 7 or 8 in girls and age 8 or 9 in boys. Adrenarche is a poorly understood phenomenon, peculiar to higher primates, that is characterized by a gradual rise in adrenal androgen production. It precedes puberty but is not casually linked to it. Early adrenarche is not associated with early puberty or with any reduction in final height or overt androgenization. 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/DHEAS levels increase until the age of 20 to a maximum 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/DHEAS replacement in older individuals have not produced convincing benefits. However, in younger and older patients with primary adrenal failure, the addition of DHEA/DHEAS to corticosteroid replacement has been shown in some studies to improve mood, energy, and sex drive.

Elevated DHEA/DHEAS levels can cause signs or symptoms 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 DHEAS levels are idiopathic. However, pronounced elevations of DHEA/DHEAS may be indicative of androgen-producing adrenal tumors. In small children, congenital adrenal hyperplasia (CAH) due to 3 beta-hydroxysteroid dehydrogenase deficiency is associated with excessive DHEA/DHEAS 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 (STAR) or 17 alpha-hydroxylase deficiency is characterized by low DHEA/DHEAS levels.

For more information see Steroid Pathways.