Objectives: The aim of this specialist study is to establish, and to show if there are any treatments for depression in menopausal women. To show the benefits of combination therapy with antidepressants, hormone replacement therapy compared to monotherapy with antidepressants, and hormone replacement therapy. Materials and Methods: The development and shaping of this work was done in a systematic and retrospective review of the literature in the field of psychiatric disorders, pharmacotherapy and gynecological endocrinology with emphasis on therapeutic options. They used Summaries of Product Characteristics of drugs registered in these studied treatment groups: the database interaction Lexicomp and Drugs.com, and search of the database PubMed for keywords: antidepressants, antidepressive effects of estrogen, depression, depression in women, hormone replacement therapy, interactions of antidepressants, estrogen-serotonin interactions, combined therapy in depression, postmenopausal depression. On the basis of selected works, knowledge of certain drugs, their pharmacokinetics, pharmacodynamics conclusions were made, and proper consideration of the studied subject. Conclusion: The possibility of combination therapy is based first of all on the fact of how changes in the reproductive status affect the response to treatment with antidepressants. While estrogen monotherapy provides solutions in terms of mitigation of somatic and mild symptoms. For women in perimenopausal, antidepressant monotherapy has its place with women who have a contraindication to the use of estrogen or after completion of their application. Regarding to the review of the interaction of these two classes of drugs, it is recommended that priority should be given to antidepressants which do not use CYP3A4, CYP1A2 isoenzyme, and avoid St. John's wort as a possible antidepressant of choice. The best results of the combined treatment with estrogen showed selective serotonin reuptake inhibitors (SSRI). Better response to SSRI administered in combination with hormone replacement therapy has been noticed during the late perimenopausal and the first year after menopause, and postmenopausal in comparison to estrogen monotherapy and placebo. Since depression is significantly heavier and is resistant to usual antidepressants, that postmenopausal combined therapy offers better therapeutic result.