Endocrine ,neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women

Abstract

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of β-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women.

Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day) ,the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day ,estradiol 50 μg/patch) and the third with transdermal estradiol alone (n = 6) (50 μg/day). Before and after 1 ,2 and 3 months of therapy ,the following circulating steroid and protein hormone levels were evaluated: DHEA ,DHEAS ,androstenedione ,testosterone ,estrone ,estradiol ,17-hydroxyprogesterone ,sex hormone-binding globulin (SHBG) ,follicle-stimulating hormone (FSH) ,luteinizing hormone (LH) ,β-endorphin ,growth hormone (GH) and Cortisol ,and a Kupperman score was performed. Before and after treatments ,plasma β-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine ,an a₂-presynaptic adrenergic agonist (1.25 mg IV); (b) naloxone ,an opioid receptor antagonist (4 mg IV) and (c) fluoxetine ,a serotonin selective reuptake inhibitor (30 mg PO).

In both groups of women treated with DHEAS ,mean basal serum DHEA ,DHEAS ,androstenedione ,and testosterone levels significantly increased after treatment ,while no changes were shown in the group receiving estradiol alone. Serum estradiol ,estrone ,GH and plasma β-endorphin levels significantly increased progressively for the three months of treatment ,with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG ,Cortisol ,and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine ,naloxone and fluoxetine stimuli failed to modify circulating β-endorphin levels. After each of the treatments ,the β-endorphin response was completely restored and was similar ,independent of the kind of therapy.

Restoration of the β-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary β-endorphin secretion ,which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.

Key Words:

• DHEAS
• Postmenopause
• β-Endorphin
• Neuroendocrine Tests
• Behavior
• Clonidine
• Naloxone
• Fluoxetine