Although DHEA-S itself is hormonally inert, it has been thought that it can be converted back into DHEA, which is weakly androgenic and estrogenic, and that DHEA in turn can be transformed into more potent androgens like testosterone and dihydrotestosterone (DHT) as well as estrogens like estradiol. As such, it has been thought that DHEA-S is a prohormone with the potential for androgenic and estrogenic effects. However, a 2005 study found that DHEA could be converted into DHEA-S but found no evidence of conversion of DHEA-S into DHEA.
DHEA-S can be converted back into DHEA via steroid sulfatase (STS). In premenopausal women, 40 to 75% of circulating testosterone is derived from peripheral metabolism of DHEA-S, and in postmenopausal women, over 90% of estrogens, mainly estrone, are derived from peripheral metabolism of DHEA-S. A study found that administration of exogenous DHEA-S in women who were pregnant increased circulating levels of estrone and estradiol. DHEA-S serves as a depot for potent androgens like testosterone and dihydrotestosterone in prostate cancer, which fuel the growth of this cancer.
The elimination half-life of DHEA-S is 7 to 10 hours, which is far longer than that of DHEA, which has an elimination half-life of only 15 to 30 minutes.
DHEA and DHEA-S are the most abundant circulating steroids in the body. Plasma levels of DHEA-S are 100 or more times higher than those of DHEA, 5 to 10 times higher than those of cortisol, 100 to 500 times those of testosterone, and 1,000 to 10,000 times higher than those of estradiol.
Levels of DHEA and DHEA-S vary throughout life. They remain low during childhood until adrenarche around 6 to 8 years of age, at which point they markedly increase, eventually peaking at around 20 to 30 years of age. From the third decade of life on, DHEA and DHEA-S levels gradually decrease. By the age of 70, levels of DHEA and DHEA-S are 20 to 30% lower than those of young adults, and in people more than 80 years of age, DHEA and DHEA-S levels can reach 80 to 90% lower than those of younger individuals.
DHEA-S levels are higher in men than in women.
The Endocrine Society recommends against the therapeutic use of DHEA-S in both healthy women and those with adrenal insufficiency, as its role is not clear from studies performed so far. The routine use of DHEA-S and other androgens is discouraged in the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, menopause due to ovarian surgery, glucocorticoid use, or other conditions associated with low androgen levels; this is because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk.
In otherwise elderly women, in whom an age-related fall of DHEA-S may be associated with menopausal symptoms and reduced libido, DHEA-S supplementation cannot currently be said to improve outcomes.
DHEA-S levels above 1890 μM/L or 700 to 800 μg/dL are highly suggestive of adrenal dysfunction because DHEA-S is made by the adrenal glands and also synthesized in the brain. The presence of DHEA-S is therefore used to rule out ovarian or testicular origin of excess androgen.
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