INFLUENCE OF TAMOXIFEN ON SEX-HORMONES, GONADOTROPINS AND SEX-HORMONEBINDING 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 sh own that tamoxifen inhibits the uptake and metabolism of E(1)S to estr adiol (E(2)) in cell cultures. To evaluate a possible influence of tam oxifen 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 cance r patients before and during tamoxifen treatment. In a subgroup of 10 patients, we measured 24 h urinary excretion of estrogen metabolites t o 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) (m ean 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 plasm a E(1) was reduced (mean reduction of 12.1%, P < 0.005). The fall in p lasma E(2) was probably secondary to a fall in plasma T (mean reductio n of 11.9%, P < 0.05) due to a reduced ovarian excretion of this andro gen. The mechanism may be a reduced gonadotrophin stimulation of the o vary, as plasma FSH and LH fell by mean values of 45.5 and 48.1%, resp ectively (P < 0.0001 for both). The increase in plasma E(1)S was accom panied by a reduced ratio of 2OHE(1)/E(1) in urine (mean reduction of 38.2%, P < 0.025) indicating reduced 2-hydroxylation. Possible mechani sms for these alterations are discussed.