ABSTRACT The biological plausibility for the effect of sex hormones on the central nervous system is now supported by a considerable amount of clinical data. This critical review guides the reader through the plethora of data, from the earliest reports of menstrual madness in the nineteenth century to neurobiological work in the new millennium. It illustrates through the scientific evidence base that, although the effect of estrogen on the central nervous system, particularly on mood and depression, remains a controversial area, there is now considerable evidence for the psychotherapeutic benefits of estrogens in the triad of hormone-responsive depressive disorders: postnatal depression, premenstrual depression and perimenopausal depression. The article also reviews the compelling data that testosterone supplementation has positive effects for depression, libido and energy, particularly where patients have only partially responded to estrogen therapy
