Abstract
Differences in the rates of affective disorders between women and men may relate to gender differences in gonadal steroid levels such as estrogen that have effects on brain monoamines important to mood regulation. Changes in estrogen secretion patterns during the perimenopause and menopause may be relevant to the increased risk for affective symptoms at that time. This study examined whether 17β-estradiol (E2) administration can modify the mood effects of experimental psychosocial stress following acute monoamine depletion in postmenopausal women. Subjects consisted of 15 normal postmenopausal women (PMW) (ages 67.1±11.2 years) blindly placed on either oral placebo or E2 (1 mg/day for 1 month, then 2 mg/day for 2 months). At the end of the 3-month treatment phase, subjects participated in three blinded depletion challenges in which they ingested each of three amino-acid mixtures: deficient in tryptophan, deficient in phenylalanine/tyrosine, or nutritionally balanced. After 5 h, subjects performed the Trier Social Stress Test (TSST), followed by mood and anxiety ratings. E2-treated subjects exhibited a significant increase in negative mood and anxiety after the TSST compared to placebo-treated women. These effects were independent of monoamine depletion and were not manifest before the TSST or at baseline. Exogenous estrogen administration in PMW may alter or modulate emotional reactivity to stressful events and may alter the sensitivity of emotional regulation. This modulation appears to be independent of alterations in monoaminergic neurotransmission. The dose of estrogen used after menopause may be important in determining the effects of gonadal steroids on emotional regulation.
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Acknowledgements
This work was supported by an independent investigator award from NARSAD and R01 AG021476 to PN, CIHR grant MOP-150051 to SNY, and GCRC M01-00109. None of the sponsors had any role in the design or conduct of the study, management, analysis, and interpretation of the data, or preparation, review, or approval of the manuscript. We thank Dori Weigand, RNC, MSN, Judy Kerr, RN, and the staff of the University of Vermont General Clinical Research Center for their efforts in support of this project and our research volunteers for their dedication to clinical research.
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A partial version of this work was previously presented as a poster at the American College of Neuropsychopharmacology Annual Meeting, San Juan, Puerto Rico, December 8–12, 2002.
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Dr Newhouse acknowledges that he is on Speaker Bureaus for Forest and Pfizer and has received research support (not for this project) in the last 12 months from Astellas, Pfizer, and Wyeth. Drs Sites, Dumas, Benkelfat, Naylor, Young, and Ms Hancur-Bucci report no potential conflicts.
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Newhouse, P., Dumas, J., Hancur-Bucci, C. et al. Estrogen Administration Negatively Alters Mood Following Monoaminergic Depletion and Psychosocial Stress in Postmenopausal Women. Neuropsychopharmacol 33, 1514–1527 (2008). https://doi.org/10.1038/sj.npp.1301530
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