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Reproductive Endocrinology |
Medical Research Council Group in Molecular Endocrinology, Centre Hospitalier de l’Universite Laval Research Center, Le Centre Hospitalier Universitaire de Québec, and Laval University, Québec, G1V 4G2, Canada
Address all correspondence and requests for reprints to: Fernand Labrie, Laboratory of Molecular Endocrinology, CHUL Research Center, 2705 Laurier Boulevard, Québec, QC, G1V 4G2, Canada.
This study analyzes in detail the serum concentration of the active
androgens and estrogens, as well as a series of free and conjugated
forms of their precursors and metabolites, after daily application for
2 weeks of 10 mL 20% dehydroepiandrosterone (DHEA) solution on the
skin to avoid first passage through the liver. In men, DHEA
administration caused 175%, 90%, 200% and 120% increases in the
circulating levels of DHEA and its sulfate (DHEA-S), DHEA-fatty acid
esters, and androst-5-ene-3ß,17ß-diol, respectively, with a return
to basal values 7 days after cessation of the 14-day treatment. Serum
androstenedione increased by approximately 80%, whereas serum
testosterone and dihydrotestosterone (DHT) remained unchanged. In
parallel with the changes in serum DHEA, the concentrations of the
conjugated metabolites of DHT, namely androsterone glucuronide,
androstane-3
,17ß-diol-G, and androstane-3ß,17ß-diol-G
increased by about 75%, 50%, and 75%, respectively, whereas
androsterone-sulfate increased 115%. No consistent change was observed
in serum estrone (E1) or estradiol (E2) in men
receiving DHEA, whereas serum E1-sulfate and
E2-sulfate were slightly and inconsistently increased by
about 20%, and serum cortisol and aldosterone concentrations were
unaffected by DHEA administration. Almost superimposable results were
obtained in women for most steroids except testosterone, which was
about 50% increased during DHEA treatment. This increase corresponded
to about 0.8 nM testosterone, an effect undetectable in men
because they already have much higher (
15 nM) basal
testosterone levels. In women, the serum levels of the conjugated
metabolites of DHT, namely androsterone glucuronide,
androstane-3,17ß-diol-G, androstane-3ß,17ß-diol-G, and
androsterone-sulfate were increased by 125%, 140%, 120% and 150%,
respectively. The present study demonstrates that the serum
concentrations of testosterone, DHT, E1, and E2
are poor indicators of total androgenic and estrogenic activity.
However, the esterified metabolites of DHT appear as reliable markers
of the total androgen pool, because they directly reflect the
intracrine formation of androgens in the tissues possessing the
steroidogenic enzymes required to transform the inactive precursors
DHEA and DHEA-S into DHT. As well demonstrated in women, who synthesize
almost all their androgens from DHEA and DHEA-S, supplementation with
physiological amounts of exogeneous DHEA permits the biosynthesis of
androgens limited to the appropriate target tissues without leakage of
significant amounts of active androgens into the circulation. This
local or intracrine biosynthesis and action of androgens eliminates the
inappropriate exposure of other tissues to androgens and thus minimizes
the risks of undesirable masculinizing or other androgen-related side
effects of DHEA.
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