ObjectiveFemale sexual hormones (estrogens and gestagens) may affect neurocognitive functioning and mood. Thus, the use of oral hormonal contraceptives (OHC) bears the risk of psychiatric adverse drug reactions such as depression and psychosis. However, the available empiric evidence regarding this connection is conflicting, and, moreover, female sex hormones seem to feature also mood-stabilizing and antidepressive effects. Hence, individual susceptibility factors and preparation-specific pharmacologic properties might play a pivotal role in the development of mood disturbances related to OHC. Single case reports provide empiric data for further systematic approaches. MethodsA clinical case is presented and discussed. ResultsA 36-year-old female patient with recurrent major depressive disorder developed rapid relapse in depression after initialization of OHC with ethinyl estradiol 30 μg/chlormadinone acetate 2 mg. This OHC combination was described to particularly feature positive effects on depressive mood. ConclusionsOHC may induce serious mood disturbances and should be administered with care, particularly in patients with affective disorders.