Title:Neurobiological Underpinnings of the Estrogen - Mood Relationship
Volume: 8
Issue: 3
Author(s): Whitney Wharton, Carey E. Gleason, Olson Sandra, Cynthia M. Carlsson and Sanjay Asthana
Affiliation:
Keywords:
Affect, Cognition, Estrogen Therapy, Hormone Therapy, Mood, Women’s Health Initiative, Neuroendocrinology, Menopause, Amygdala, Estrogen
Abstract: Women are at a higher risk than men to develop mood disorders and depression. The increased risk is
associated with fluctuating estrogen levels that occur during reproductive cycle events, particularly during the menopausal
transition, a time characterized by drastic fluctuations in estrogen levels and increases in new onset and recurrent
depression. Conversely, recent data show that hormone therapy, particularly transdermal estradiol formulations, may
prevent mood disorders or even serve as a treatment regimen for women with diagnosed mood disturbances via estrogen
regulation. While the exact mechanism is unknown, there is compelling scientific evidence indicating the neuromodulatory
and neuroprotective effects of estrogen, which are directly relevant to mood symptomotology. Specifically,
affective regulation has been linked to neural structures rich in estrogen receptors and estrogenic regulation of
neurotransmitters. While a wealth of basic science, observational and clinical research support this rationale, potential
mediating variables, such as estrogen formulation, proximity of administration to menopause, and the addition of
progestins should be considered. Furthermore, the nature of postmenopausal exogenous hormone formulations in relation
to premenopausal endogenous levels, as well as the ratio of estrone to estradiol warrant consideration.