INTRODUCTION: Hormone replacement therapy (HRT) is prescribed to women for the treatment of postmenopausal symptoms; however, there remains doubt about what kind of influence does it have on cognition. Previous studies, in animal models and observational clinical data, showed that estrogen could have a positive effect on the aging brain; but large clinical trials, such as the Women’s Health Initiative Memory Studies (WHIMS), showed a negative effect on cognition in older women. We aimed to explore possible reasons for such inconsistency, based on the results of the clinical studies classified according to patient age, duration and type of hormone replacement therapy. ----- METHODS: We carried out a literature search for the period between January 1995 to May 2018 in three databases (PubMed, Embase, Cochrane) using the following keywords: progesterone, estrogen, cognition. Inclusion criteria were the following: randomized controlled trial, cognition test(s), no additional pharmacological manipulations, no phytoestrogens/herbal preparations or selective estrogen receptor modulators (SERMs). ----- RESULTS: After application of the inclusion criteria, a total of 34 (35) articles out of 7,086 were included. Regarding the duration of therapy, 3 studies used acute (≤1 month), 18 subacute (1 month - 1 year) and 14 used chronic therapy (≥1 year). Most of the studies, (20/36) showed that HRT had no effect on cognition; whereas, an additional 6 showed positive influence on verbal cognition in younger women (medroxyprogesterone acetate was not the part of HRT). The remaining 9 studies showed a negative effect on cognition (6/9 done in older patients). ----- CONCLUSION: There is evidence of a positive effect with the use of unopposed estrogen or estrogen/micronized progesterone in younger women, with acute and subacute therapy. There is a negative effect on cognition with the use of conjugated equine estrogen/medroxyprogesterone acetate in older postmenopausal women. The great majority of studies included in our research showed that HRT had no effect on cognition. Future studies should focus on the research effect of natural progesterone and estrogen in younger postmenopausal women.