1.
Interactive effects of estrogen and serotonin on brain activation during working memory and affective processing in menopausal women.
Epperson, CN, Amin, Z, Ruparel, K, Gur, R, Loughead, J
Psychoneuroendocrinology. 2012;(3):372-82
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Abstract
While cognitive changes and mood instability are frequent symptoms reported by menopausal women, the degree to which the decline in estrogen production is responsible is not yet clear. Several lines of evidence suggest that estrogen may produce its effects on cognition and mood through modulation of serotonergic function. To test this hypothesis, we used the tryptophan depletion (TD) paradigm to lower central serotonin levels and pharmacologically manipulated estrogen levels in healthy menopausal women. We examined the individual and combined effects of estradiol and serotonin on working memory, emotion processing and task-related brain activation. Eight healthy predominantly early postmenopausal women underwent TD or sham depletion followed by functional magnetic resonance imaging (fMRI) both before and after short-term transdermal estradiol 75-150 μg/d administration. There was an estradiol treatment by TD interaction for brain activation during performance on both the N-back Task (working memory) and Emotion Identification Task (affective processing). During the 2-back condition, TD attenuated activation prior to, but not after, estradiol treatment in the right and left dorsal lateral prefrontal and middle frontal/cingulate gyrus. During emotion identification, TD heightened activation in the orbital frontal cortex and bilateral amygdala, and this effect was attenuated by estradiol treatment. These results provide preliminary evidence that serotonergic effects directly mediate the impact of estrogen on brain activation during working memory and affective processing.
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Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids.
Genazzani, AD, Stomati, M, Bernardi, F, Pieri, M, Rovati, L, Genazzani, AR
Fertility and sterility. 2003;(6):1495-501
Abstract
OBJECTIVE To evaluate the effects of a low-dose DHEA supplementation on hormonal parameters in early and late postmenopausal women. DESIGN Prospective case study. SETTING Postmenopausal women in a clinical research environment. PATIENT(S): Twenty postmenopausal women were divided in two groups according to age (50-55 and 60-65 years). INTERVENTION(S): All patients underwent hormonal evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA orally). Pelvic ultrasound examination and Kupperman score were performed before and after 3, 6, and 12 months of therapy. MAIN OUTCOME MEASURE(S): Plasma DHEA, DHEAS, estrone (E1), E2, P, androstenedione (A), T, dihydrotestosterone, 17alpha-hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, beta-endorphin, sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations. RESULT(S): The levels of all the steroids that derive from DHEA metabolism increased in plasma with DHEA administration. Also neurosteroids (namely allopregnanolone) and endorphin showed increased plasma levels, whereas both gonadotropins were significantly reduced. Endometrial thickness did not change throughout the study period. CONCLUSION(S): Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climateric symptoms, similarly to estroprogestin replacement therapy. These data suggest that DHEA supplementation is a more effective replacement therapy than a simple "dietary supplement."