Several forms of depression are unique to women becauseof their apparent association with changes in gonadal hor-mones, which in turn modulate neuroregulatory systemsassociated with mood and behavior. This review examinesthe evaluation and treatment of depression that occurspremenstrually, postpartum, or in the perimenopause onthe basis of current literature. The serotonergic antide-pressants consistently show efficacy for severe premen-strual syndromes (PMSs) and premenstrual dysphoric dis-order (PMDD), and are the first-line treatment for thesedisorders. The use of antidepressants for postpartumdepression is compromised by concerns for effects in theinfants of breast-feeding mothers, but increasing evidencesuggests the relative safety of the antidepressant medica-tions, and the risk calculation should be made on an indi-vidual basis. Estradiol may be effective for postpartumdepression and for moderate-to-severe major depressionin the perimenopause. In spite of its frequent use, proges-terone is not effective for the mood and behavioral symp-toms of PMS/PMDD, postpartum depression, or peri-menopausal depressive symptoms.Dialogues Clin Neurosci. 2002;4:177-191.pproximately 20% of women experience anepisode of major depression, a rate that is twice that ofmen.1 The period of greatest vulnerability for womenappears to be the childbearing years, with the initialonset of depression most likely to occur between theages of 25 and 44.2 Several forms of depression areunique to women because of their apparent associationwith changes in reproductive hormones: premenstrualdysphorias, including premenstrual syndromes (PMSs)and premenstrual dysphoric disorder (PMDD), post-partum depression (PPD), and depression in the peri-menopausal period. The link among these depressivedisorders appears to be a sensitivity to normal shifts ingonadal hormones, which affect neuroregulatory systemsthat play a role in affective disorders.3,4 Such shifts occurduring the menstrual cycle, in pregnancy and postpar-tum, and with ovarian aging in the years leading to themenopause.Historically, depression has been underrecognized andundertreated. Until recently, diagnostic criteria wereimprecise, clinical trials of purported treatments formenstrually related depressions were lacking or poorlydone, and treatment options were generally unsupportedP h a r m a c o l o g i c a l a s p e c t s1 7 7Treatment of depression associatedwith the menstrual cycle: premenstrualdysphoria, postpartum depression, andthe perimenopauseEllen W. Freeman, PhDAKeywords: depression; premenstrual syndrome; postpartum depression; peri-menopause; antidepressant; estrogen; gonadal hormone; treatmentAuthor affiliations: Research professor, Departments of Obstetrics/Gynecology and Psychiatry, University of Pennsylvania, Pa, USACorresponding author: Department of Obstetrics and Gynecology, 2Dulles/Mudd Suite, Hospital of the University of Pennsylvania, 3400Spruce Street, Philadelphia, PA 19104, USA(e-mail: freemane@mail.med.upenn.edu)