Increases in steroid binding globulins induced by tamoxifen in patients with carcinoma of the breast.

The effects of tamoxifen on cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) were studied in 25 women and one man with breast cancer. These patients were in various endocrine states according to age (15 post-menopausal women) or previous endocrine surgery (ovariectomy, two patients; ovariectomy plus adrenal surgery, five patients; hypophysectomy, three patients; ovariectomy plus hypophysectomy, two patients). The administration of tamoxifen (20-40 mg/day) resulted in increases in the level of CBG in all patients (mean rise in binding capacity 10.8 microgram cortisol/100 ml plasma) and in the level of SHBG in 21 patients (mean rise in binding capacity 0.79 microgram dihydrotestosterone/100 ml plasma for all patients). These increases were positively correlated. They were not associated with any alteration in the association constants of the steroid binding globulins. The effect of tamoxifen on CBG diminished with increasing age. The changes in the levels of CBG and SHBG were independent of the endocrinological state of the patient. It is inferred that tamoxifen has a direct oestrogen-like action on the liver which results in increased production of CBG and SHBG. Tamoxifen therapy for carcinoma of the breast appeared to be least effective in those patients in whom the drug caused the highest increase in the concentration of CBG.