INFLUENCE OF TAMOXIFEN ON SEX-HORMONES, GONADOTROPINS AND SEX-HORMONE BINDING GLOBULIN IN POSTMENOPAUSAL BREAST-CANCER PATIENTS

Estrone sulphate (E(1)S) may be an important estrogen source in breast cancers, particularly in postmenopausal women. Recent studies have shown that tamoxifen inhibits the uptake and metabolism of E(1)S to estradiol (E(2)) in cell cultures. To evaluate a possible influence of tamoxifen on E(1)S disposition in vivo, we measured plasma levels of E(1)S together with unconjugated estrogens (E(1) and E(2)), androgens (T, A, DHEA and DHEAS), SHBG, FSH and LH in 32 postmenopausal breast cancer patients before and during tamoxifen treatment. In a subgroup of 10 patients, we measured 24 h urinary excretion of estrogen metabolites to evaluate the influence of tamoxifen treatment on estrogen metabolism and total estrogen production. Tamoxifen increased plasma levels of E(1)S (mean increase of 18.1%, P < 0.05) and the ratio of E(1)S/E(1) (mean increase of 25.7%, P < 0.01) and E(1)S/E(2) (mean increase of 34.7%, P < 0.0005). No significant change in plasma E, was seen, but plasma E(1) was reduced (mean reduction of 12.1%, P < 0.005). The fall in plasma E(2) was probably secondary to a fall in plasma T (mean reduction of 11.9%, P < 0.05) due to a reduced ovarian excretion of this androgen. The mechanism may be a reduced gonadotrophin stimulation of the ovary, as plasma FSH and LH fell by mean values of 45.5 and 48.1%, respectively (P < 0.0001 for both). The increase in plasma E(1)S was accompanied by a reduced ratio of 2OHE(1)/E(1) in urine (mean reduction of 38.2%, P < 0.025) indicating reduced 2-hydroxylation. Possible mechanisms for these alterations are discussed.