The adrenal production of the delta 5-androgens,
dehydroepiandrosterone (
DHEA) and its
sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that
DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month
DHEA supplementation in early and late postmenopausal women, with normal or
overweight body mass index (BMI), on the level of circulating
steroids,
sex hormone binding globulin (SHBG),
beta-endorphin and
gonadotropins, and on the adrenal gland response to
dexamethasone suppression and
adrenocorticotropic hormone (
ACTH) stimulation. Early postmenopausal women (50-55 years) both normal weight (BMI 20-24, n = 9) and
overweight (BMI 26-30, n = 9) and late postmenopausal women (60-65 years) both of normal weight and
overweight, were treated with oral
DHEA (50 mg/day). Circulating
DHEA, DHEAS, 17-OH
pregnenolone,
progesterone, 17-OH
progesterone, allopregnenolone,
androstenedione,
testosterone,
dihydrotestosterone,
estrone,
estradiol, SHBG,
cortisol,
luteinizing hormone,
follicle stimulating hormone and
beta-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal
steroid levels were used to assess the relative activities of the adrenal cortex
enzymes. Before and after 3 and 6 months of
therapy, each women underwent an
ACTH stimulating test (10 micrograms i.v. in bolus) after
dexamethasone administration (0.5 mg p.o.) to evaluate the response of
cortisol,
DHEA, DHEAS,
androstenedione, 17-OH
pregnenolone,
allopregnanolone,
progesterone and 17-OH
progesterone. The between-group differences observed before treatment disappeared during
DHEA administration. Levels of 17-OH
pregnenolone remained constant during the 6 months. Levels of
DHEA, DHEAS,
androstenedione,
testosterone and
dihydrotestosterone increased progressively from the first month of treatment. Levels of
estradiol and
estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in
overweight late postmenopausal women, while the other groups showed constant levels.
Progesterone levels remained constant in all groups, while 17-OH
progesterone levels showed a slight but significant increase in all groups.
Allopregnanolone and plasma
beta-endorphin levels increased progressively and significantly in the four groups, reaching values three times higher than baseline. Levels of
cortisol and
gonadotropins progressively decreased in all groups. The product/precursor ratios of adrenal
steroid levels at the sixth month were used to assess the relative activities of the adrenal cortex
enzymes and were compared to those found before
therapy. The
17,20-desmolase,
sulfatase and/or
sulfotransferase,
17,20-lyase and
5 alpha-reductase activities significantly increased, while the 3 beta-hydroxysteroid-
oxidoreductase activity did not vary. On the contrary, the 11-hydroxylase and/or
21-hydroxylase activities showed a significant decrease after 6 months of treatment. In basal conditions,
dexamethasone significantly suppressed all the adrenal
steroids and this suppression was greater after 3 and 6 months of treatment for
DHEA, DHEAS and
allopregnanolone, while it remained unchanged for other
steroids. Before treatment,
ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in delta 5- and delta 4-androgens,
progesterone and 17-OH
progesterone, while
cortisol responded less in both younger and older normal-weight women. The endometrial thickness did not show significant modifications in any of the groups of postmenopausal women during the 6 months of treatment. Treatment with
DHEA was associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in