Increased interest in the complex interplay between gonadal steroids and neurotransmitter systems involved in mood has led investigators to question the role of gonadal steroids in the treatment of affective disorders, especially in women.ObjectivesThe purpose of this article is to provide a rationale for using gonadal hormones in the treatment of depression in women.MethodsThe literature is reviewed regarding 1) sex-specific phenomenologic and epidemiologic differences in the manifestation of psychiatric illness, 2) sex-specific differences in the therapeutic and adverse effects of psychotropic medications, 3) the complex interplay between gonadal steroids and neurotransmitter systems implicated in psychiatric disorders, and 4) the growing literature regarding the use of estrogen and progesterone in the treatment of mood disorders in women and androgens in the treatment of depression and sexual dysfunction in both men and women.ResultsFindings from pharmacologic trials of estrogen and androgens are encouraging, albeit mixed, in the treatment of mood disorders and decreased libido in women, respectively. Controlled studies have failed to confirm early open-label reports of the effectiveness of progesterone in the treatment of premenstrual syndrome.ConclusionsPending replication, estrogen may become an important pharmacologic agent in the treatment of postnatal and perimenopausal depression, whereas androgens have been shown to improve libido in postmenopausal women and hypogonadal men. Progesterone cannot be recommended as a treatment for premenstrual sydrome or postnatal depression.