The physiological importance and therapeutical interest of
dehydroepiandrosterone (
DHEA) and its
sulfate ester (DHEAS) are still controversial.
Panhypopituitarism is characterized by the absence of secretion of adrenal and gonadal
steroids and thus the production of their metabolites. The conversion of
DHEA given orally into delta 5 derivatives,
androgens,
androgen metabolites, and
estrogens was studied in ten patients with complete
panhypopituitarism. Sex
steroid therapy was withdrawn for at least 2 months. Each patient received, at 1-month intervals and in a random order, two single oral doses of
DHEA (50 mg and 200 mg) and placebo. During each treatment, urine samples were collected for 24 h, and blood samples were drawn at hourly intervals for 8 h. In patients with pituitary deficiency, plasma
DHEA and DHEAS were not detectable and increased, with the 50 mg dose, up to levels observed in young adults. The administration of 200 mg of
DHEA induced an increase of both
steroids to supraphysiological plasma levels. A small increase of
delta 5-androstenediol was observed. In contrast, the increase of plasma delta 4-androstenedione was important and dose dependent.
DHEA was also converted into the potent sex
steroid testosterone (T). The administration of a 50 mg dose of
DHEA restored plasma T to levels similar to those observed in young women. The 200 mg dose induced an important increase of plasma T, slightly below the levels observed in normal men. The increase of plasma
dihydrotestosterone levels was small at both doses of
DHEA, in contrast with the large conversion of
DHEA into
androsterone glucuronide and androstanediol
glucuronide. Finally,
DHEA administration induced a significant and dose dependent increase of plasma
estrogens and particularly of
estradiol. In conclusion, this short term study demonstrates that: 1)
panhypopituitarism is a model of interest to study the metabolism of
DHEA; 2) in the absence of
pituitary hormones and of adrenal and gonadal
steroids,
DHEA given orally is mainly converted into delta 4 derivatives, which in turn are strongly metabolized into 5 alpha-3keto-reduced
steroids; 3) a significant increase of sex active
hormones was observed in plasma after 200 and even 50 mg of
DHEA. Thus, biotransformation of
DHEA into potent
androgens and
estrogens may explain several of the reported beneficial actions of this
steroid in aging people.