Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause

The adrenal production of the Delta5-androgens, dehydroepiandrosterone (DHE A) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines l inearly with aging. The evidence that DHEA or DHEAS administration may alle viate 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 n ormal or overweight body mass index (BMI), on the level of circulating ster oids, sex hormone binding globulin (SHBG), beta -endorphin and gonadotropin s, and on the adrenal gland response to dexamethasone suppression and adren ocorticotropic 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 y ears) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnanolone, androstenedione, testosterone, dihydrotesto sterone, 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 ste roid levels were used to assess the relative activities of the adrenal cort ex enzymes. Before and after 3 and 6 months of therapy, each women underwen t an ACTH stimulating test (10 mug i.v, in bolus) after dexamethasone admin istration (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 dihy drotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/sec ond month of treatment. Levels of SHBG significantly decreased from the sec ond month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained const ant in all groups, while 17-OH progesterone levels showed a slight but sign ificant increase in all groups. Allopregnanolone and plasma beta -endorphin levels increased progressively and significantly in the four groups, reach ing values three rimes higher than baseline. Levels of cortisol and gonadot ropins progressively decreased in all groups. The product/precursor ratios of adrenal steroid levels at the sixth month were used to assess the relati ve activities of the adrenal cortex enzymes and were compared to those foun d before therapy. The 17,20-desmolase, sulfatase and/or sulfotransferase, 1 7,20-lyase and 5 alpha -reductase activities significantly increased, while the 3 beta -hydroxysteroid-oxidoreductase activity did not vary. On the co ntrary, the 11-hydroxylase and/or 21-hydroxylase activities showed a signif icant 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 treatmen t for DHEA, DHEAS and allopregnanolone, while it remained unchanged for oth er steroids. Before treatment, ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in Delta5-and Delta4-androgens, progesterone and 17-OH progesterone, while cor tisol responded less in both younger and older normal-weight women. The end ometrial thickness did not show significant modifications in any of the gro ups of postmenopausal women during the 6 months of treatment. Treatment wit h DHEA war associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in the early p ostmenopausal women. In conclusion, the present findings confirm that DHEA supplementation produ ces physiological and supraphysiological modifications in steroid milieu an d adrenal function. The beneficial effects of DHEA on the quality of life a nd in reverting the aging process may be related to changes in the release of adrenal products and/or peripheral steroids, with an increase in anxioly tic (allopregnanolone), anabolic (androstenedione, (estrone, erone, dihydro testosterone) and estrogenic (estrone, estradiol) molecules, a beneficial d ecrease in cortisol and increase in pituitary beta -endorphin production.