Metabolism of DHEA in postmenopausal women following percutaneous administration.
The marked decline in serum dehydroepiandrosterone (DHEA) with age is believed to play a role in health problems associated with aging, these health issues being potentially preventable or reversible by the exogenous administration of DHEA. In the present study, liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and gas chromatrography/mass spectrometry (GC/MS) were used to measure the serum levels of DHEA and 11 of its metabolites in seventy-five 60-65-year-old Caucasian women who received 3g of 0.1%, 0.3%, 1.0% or 2.0% DHEA cream or placebo applied twice daily on the face, upper chest, arms and legs. The serum levels of DHEA increased 574% over control at the 2.0% DHEA dose while the sum of the androgen metabolites androsterone glucuronide (ADT-G), 3alpha-androstenediol-3G (3alpha-diol-3G) and 3alpha-diol-17G increased by only 231%. On the other hand, serum testosterone and dihydrosterone were increased by 192% and 275%, respectively, above basal levels compared to 139% and 158% for estrone and estradiol. Such data show that the transformation of exogenous DHEA in postmenopausal women is preferentially into androgens rather than into estrogens. On the other hand, the present data indicate that serum DHEA measurements following DHEA supplementation in postmenopausal women are an overestimate of the formation of active androgens and estrogens and suggest a decreased efficiency of transformation of DHEA into androgens and estrogens with aging.
Labrie
Fernand
F
Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Canada. fernand.labrie@crchul.ulaval.ca
Bélanger
Alain
A
Bélanger
Patrick
P
Bérubé
René
R
Martel
Céline
C
Cusan
Leonello
L
Gomez
José
J
Candas
Bernard
B
Chaussade
Véronique
V
Castiel
Isabelle
I
Deloche
Claire
C
Leclaire
Jacques
J
D000279:Administration, Cutaneous; D000368:Aged; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D010919:Placebos; D017698:Postmenopause / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D010919:Placebos; D003687:Dehydroepiandrosterone