estrone-sulfate and droloxifene

Droloxifene (3-hydroxytamoxifen) is a novel antiestrogen currently undergoing clinical investigations for treatment of breast cancer patients. We measured plasma levels of sex hormone binding globulin (SHBG) and the gonadotrophins (LH and FSH) at baseline and after 3 months on treatment in a group of fourteen postmenopausal women treated with droloxifene 40 mg daily. Plasma levels of estrone (E1), estradiol (E2) and estrone sulphate (E1S) were measured in a subgroup of eight patients. Plasma SHBG increased during treatment with droloxifene by a mean value of 16.6% (P < 0.05), while plasma levels of LH and FSH decreased by a mean value of 15.7% (n.s.) and 18.1% (P < 0.05), respectively. Plasma levels of E2 and E1 fell slightly (mean decrease 19.4 and 16.7% respectively, n.s.). On the contrary, plasma levels of E1S increased by a mean value of 23.5% (P = 0.068). The ratio of E1S to E1 and E1S to E2 increased by a mean value of 48.3% (P < 0.025) and 53.2% (P < 0.025), respectively. The effect of droloxifene 40 mg daily on plasma levels of SHBG resembles what is seen during treatment with tamoxifen but occurs to a smaller extent. Contrary to tamoxifen, droloxifene caused a minor suppression of plasma LH levels, suggesting droloxifene to have less estrogen agonistic effects on the pituitary.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Estradiol; Estrogens; Estrone; Female; Follicle Stimulating Hormone; Follow-Up Studies; Humans; Luteinizing Hormone; Postmenopause; Sex Hormone-Binding Globulin; Tamoxifen; Time Factors

Plasma levels of oestradiol (Oe2), oestrone (Oe1) oestrone sulphate (Oe1S), androstenedione, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG) and the gonadotrophins (FSH and LH) were determined in 20 postmenopausal women with breast cancer treated with the anti-oestrogen droloxifene (3-hydroxytamoxifen). Plasma oestrogens were measured before and after 3, 6 and 12 months of therapy. The other hormones were measured before and after 6 months of therapy. Droloxifene treatment had no significant influence on plasma levels of Oe2. Plasma levels of Oe1 and Oe1S increased during treatment (mean increase of 11.9-15.9% and 24.5-69.4% respectively after different time-intervals on treatment). The Oe1S/Oe1 and Oe1S/Oe2 ratios increased by mean values of 13.8-45.2% and 25.9-52.4% respectively. Plasma SHBG increased significantly by a mean value of 73.9%, while FSH and LH fell non-significantly by 19.7% and 20.4% respectively. Plasma levels of testosterone, androstenedione, DHEA and DHEAS all increased during treatment, but none of these alterations were of statistical significance. While the influence of droloxifene on plasma SHBG resembled that which is seen during treatment with tamoxifen, its influence on plasma oestrogens and the gonadotrophins seems to be different. Possible explanations of such differences and the clinical implications of alterations in plasma hormones during treatment with droloxifene are discussed.

Topics: Aged; Breast Neoplasms; Estradiol; Estrogen Antagonists; Estrogens, Conjugated (USP); Estrone; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Luteinizing Hormone; Middle Aged; Postmenopause; Sex Hormone-Binding Globulin; Tamoxifen; Time Factors