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).