Influence of the catechol‐O‐methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women

BACKGROUND: Catechol‐O‐methyltransferase (COMT) is the principal enzyme in the conjugation pathway for hydroxylated estrogens. We hypothesize that blood 17β‐estradiol (E2) and estrone (E1) levels in postmenopausal women receiving an oral E2 preparation are dependent on the enzyme activity of COMT. METHODS: To determine the influence of this enzyme on E2 serum levels three groups of 12 selected from 159 healthy normotensive postmenopausal women were selected according to their codon 158 COMT genotype (COMTHH, COMTHL, COMTLL) which is known to be associated with enzyme activity. All selected women received one 2 mg tablet estradiol valerate and blood samples were taken before treatment and after 1, 3 and 48 h. RESULTS: After 3 h the serum levels of E2 were significantly higher in women with the COMTLL genotype (median 69 pg/ml, range 58–91) and the COMTHL genotype (median 69 pg/ml, range 43–84) compared with women with the COMTHH genotype (median 45 pg/ml, range 15–68, P < 0.005). In a univariate analysis of variance, considering age, body weight, and COMT genotype, body weight (P = 0.034) and COMT genotype (P < 0.001) were independently related to the increase of serum E2 levels, whereas age was not. CONCLUSIONS: Our data demonstrate that serum E2 levels significantly correlate with the COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases such as hormone‐dependent cancers, coronary heart disease and on efficacy of hormone replacement therapy.