Hormone replacement therapy (HRT) is highly effective for women suffering from climacteric symptoms, with occasionally severe side effects. To determine which women needs HRT for climacteric symptoms indeed, pharmacogenetical approach for HRT was performed. Under the condition of minimal HRT, 33 patients required HRT for more than 1 year and the remaining 156 did not. Three single nucleotide polymorphisms (SNPs) in estrogen receptor alpha (ER alpha) gene and 3 SNPs and a microsatellite polymorphism in estrogen receptor beta (ER beta) gene were analyzed using LightTyper and PCR. Homozygous for 18 CA repeats of D14S1026 (OR 8.00, 95% CI 2.56-25.02, P < 0.001) and rs1256049 (OR 6.35, 95% CI 2.38-16.92, P = 0.004) in ER beta associated with minimal HRT. In contrast, rs1271572 in 789 bp upstream region of ER beta (OR 0.30, 95% CI 0.14-0.65, P = 0.002) gene decreased HRT. rs2228480 in ER alpha gene also increased HRT. Tailored decisions can be expected on the future use of HRT referring genetic polymorphisms of individuals. (c) 2008 Published by Elsevier Inc.