Sex hormones and biomarkers of neuroprotection and neurodegeneration: implications for female reproductive events in bipolar disorder

Abstract

Previous studies have suggested that women with bipolar disorder are at higher risk for mood episodes during periods of intense hormonal fluctuation (e.g., premenstrual, postpartum, perimenopause). There is converging literature showing that estrogen and progesterone can modulate neurotransmitter systems and intracellular signaling pathways known to be affected by mood stabilizing agents. Here, we critically review clinical aspects of reproductive cycle events in women with bipolar disorder and preclinical studies, with a focus on the functional interactions between sex hormones and biomarkers of neuroprotection and neurodegeneration that are thought to be involved in the neurobiology of bipolar disorder: brain-derived neurotrophic factor, oxidative stress, and inflammation. A MedLine search using estrogen, progesterone, brain-derived neurotrophic factor, oxidative stress, and inflammation as key words was conducted. Data showed that estrogen and progesterone closely interact with brain-derived neurotrophic factor, oxidative stress, and inflammation pathways. This relationship between sex hormones and the pathways of neuroprotection/neurodegeneration may be relevant to the psychopathological aspects of bipolar disorder in women.