Potent inhibition by tamoxifen of spontaneous and agonist-induced contractions of the human myometrium and intramyometrial arteries.

OBJECTIVE

Our purpose was to elucidate the mechanism of direct (nongenomic) action of antiestrogens on spontaneous and agonist-induced contractions of the human myometrium and uterine arteries.

STUDY DESIGN

Myometrial strips and pieces of uterine arteries were obtained from nonpregnant premenopausal women undergoing hysterectomy. Spontaneous activity of myometrium and responses of myometrium and artery to K(+)-depolarization and vasopressin were recorded under isometric conditions. Quantification of the responses was done by planimetry.

RESULTS

The 50% inhibitory concentration values for tamoxifen, clomiphene, and cyclofenil in the case of myometrial spontaneous activity were 2.8, 43, and 331 nmol/L, respectively. Vasopressin-induced contractions in both the myometrium and arteries were potently inhibited by tamoxifen, and the 50% inhibitory concentration for the myometrium (1.4 nmol/L) was significantly lower (p < 0.05) than that for the arteries (11 nmol/L). Although tamoxifen caused no inhibition of responses induced by high potassium chloride (80 mmol/L), responses induced by low potassium chloride (20 mmol/L) were inhibited by 40% to 50% in both the myometrium and arteries. Glibenclamide reversed the inhibition by tamoxifen of spontaneous myometrial activity.

CONCLUSIONS

Tamoxifen is a highly potent inhibitor of the contractile activity of the human nonpregnant myometrium and uterine arteries. It is suggested that tamoxifen could have strong potential in the treatment of dysmenorrhea.