TITLE:
Hormonal Treatments for Bipolar Disorder: A Review of the Literature
AUTHORS:
Tuong-Vi Nguyen, Nancy C. P. Low
KEYWORDS:
Tamoxifen; Hormone Replacement Therapy; Oral Contraceptives; Mood; Mania; Depression
JOURNAL NAME:
Journal of Behavioral and Brain Science,
Vol.2 No.1,
February
29,
2012
ABSTRACT: Hormonal therapies may play a role in the treatment of bipolar disorder. Preliminary evidence suggests that: 1) tamoxifen has anti-manic properties; 2) hormone replacement therapy represents a good augmentation strategy in treatment-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 increasing GABAA receptor activation through its active metabolite allopregnanolone, which may be the basis of its anxiolytic, 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 osteoporosis 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 contra-indications to other psychotropic medications are present. Institution of regular monitoring for medical complications and drug-drug interactions are essential to minimize risks and maximize benefits.