Hormonal Treatments for Bipolar Disorder: A Review of the Literature

Abstract

Hormonal therapies may play a role in the treatment of bipolar disorder. Preliminary evidence suggests that: 1) Ta-moxifen has anti-manic properties; 2) Hormone replacement therapy represents a good augmentation strategy in treat-ment-resistant peri-menopausal depression; and 3) Certain oral contraceptives could prevent menstrual exacerbations of affective symptoms. Potential neurobiological mechanisms of the anti-manic effects of tamoxifen include the inhibition of protein kinase C in addition its anti-estrogenic effects. Estrogen is a serotonergic and adrenergic agonist as well as an agent promoting neurogenesis in the hippocampus through glutamatergic synaptic formation, which may be the basis of its antidepressant activity. Progesterone appears to decrease serotonergic and adrenergic tone and activity, while in-creasing GABA A receptor activation through its active metabolite allopregnanolone, which may be the basis of its anx-iolytic, sedative, and potentially anti-manic properties. Although there is consistency between the evidence for clinical efficacy and neurobiological mechanisms of hormonal treatments, the current state of knowledge relies on studies with several methodological limitations. On the other hand, benefits of hormonal treatment include protection from osteopo-rosis and several gynecological cancers, as well as safe contraception in a population at-risk for unplanned pregnancy. Nonetheless, hormonal treatments should be reserved for treatment-resistant bipolar depression or mania, or when con-tra-indications to other psychotropic medications are present. Institution of regular monitoring for medical complica-tions and drug-drug interactions are essential to minimize risks and maximize benefits.