Objective: To study the effectiveness and reliability of estrogen treatment on Alzheimer disease, and analyze the possible reason of the controversy between domestic and abroad researches. Data sources: Using the key terms "estrogen and Alzheimer or cognition or human brain or neuroprotection" and "hormone replacement therapy and ovarian cancer", we searched the MEDLINE database in English from January 2000 to December 2004. Meanwhile, using the key terms "estrogen and Alzheimer Disease", we searched the Chinese journals full-text database in Chinese from January to December 2004. Study selection: All articles were selected firstly, and those contained treatment group and control group were selected. The non-randomized controlled trials were excluded and the rest full text was looked up to judge whether they were randomized clinical trials. The inclusion criteria were: 1 It should be randomized controlled trial whatever they were single-blind, double-blind or non-blind. 2 The control group was placebo group. 3 The treatment group was estrogen treatment group and estrogen and progestogen therapy group. 4 The objects observed were Alzheimer disease or mild cognitive impairment diagnosed by Diagnostic and Statistical Manual of Mental Pisorder IV. Data extraction: A total of 19 articles were collected, 11 were relevant to randomized or non-randomized trials about the estrogen treatment on Alzheimer disease, and 8 were about American Women's Health Initiative trial. Fourteen articles met inclusion criteria, and 5 articles were exluded because of duplicated summarizations. Data synthesis: Totally 61 299 patients were involved in 14 tests, which assessed the estrogen treatment on Alzheimer disease. Several side effects showed in 4 tests and they were mainly ovarian cancer, breast cancer, thromboembolic disease and stroke. Conclusion: There is not enough evidence to prove the definite effect of estrogen treatment on Alzheimer disease, nor there is enough evidence to prove the side effect.