Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium

Objective: To determine the effects of single dose tamoxifen on plasma estrogen (E)-binding equivalents and endometrial estradiol (E₂) and progesterone (P) receptors. Design: Controlled clinical study. Setting: Normal human volunteers were studied in an academic research environment. Patients: Premenopausal and postmenopausal women with histologically normal endometrium undergoing curettage or hysterectomy were selected. Interventions: Tamoxifen was administered orally; blood and endometrial samples were collected 4 to 96 hours after tamoxifen administration. Main Outcome Measures: Plasma E-binding equivalents, endometrial cytosolic and nuclear E₂ and P receptors. Results: (1) Plasma E-binding equivalents increased eightfold at 4 to 24 hours of tamoxifen administration and declined exponentially thereafter, reaching control levels at 73 to 96 hours. Plasma E-binding equivalents were not affected by endogenous E₂ levels. (2) Endometrial total E₂ and P receptor levels increased in all women 2.9 to 19.2-fold after tamoxifen. (3) Tamoxifen resulted in an increase in the fraction of the E₂ receptor measured in the nuclear extract 2.1 to 7.5-fold in midcycle, secretory, and menopausal endometria but not in proliferative endometrium. Conclusions: (1) Tamoxifen has an E₂ agonistic effect on histologically normal human endometrium. (2) Irrespective of the total level of the endometrial E₂ receptor, the nuclear capacity of that receptor in vivo is limited (approximately 75% to 80% of the total level).