The present study examines the relationship between estrogen receptor (ER) gene polymorphism and undefined complaints to clarify the aging process of the genitospinal center. Pvu II and Xba I restriction fragment length polymorphism (RFLP) of the estrogen receptor (ER) gene and its relationships to undefined symptoms was examined in 507 Japanese peri- and postmenopausal women who were classified in 3 groups by serum estradiol (E2) values; group A:E2>30 pg/ml; group B:E210-30 pg/ml; group C:E2<10 pg/ml. The percentage of women grouped A was significantly higher than that of group B in genotype Pp. Furthermore, the frequency of Ppxx in group A was significantly higher than that of group B or C. On the other hand, the frequency of ppxx in group A was significantly lower than that of group B (p=0.0042) or C (p=0.049). Neither FSH nor LH differed significantly between Ppxx and ppxx. On the other hand, the plasma estradiol level differed significantly between Ppxx and ppxx (p=0.0004). Moreover, a higher incidence of mental symptoms was observed in group A than in groups B or C (p<0.01). The present results suggest that ER gene polymorphism influences aging of the genitospinal center, and may explain in part the pathophysiology and cause of undefined perimenopausal complaints.