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 (nonge nomic) action of antiestrogens on spontaneous and agonist-induced cont ractions of the human myometrium and uterine arteries. STUDY DESIGN: M yometrial strips and pieces of uterine arteries were obtained from non pregnant premenopausal women undergoing hysterectomy. Spontaneous acti vity of myometrium and responses of myometrium and artery to K+-depola rization and vasopressin were recorded under isometric conditions. Qua ntification of the responses was done by planimetry. RESULTS: The 50% inhibitory concentration values for tamoxifen, clomiphene, and cyclofe ril in the case of myometrial spontaneous activity were 2.8, 43, and 3 31 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 signi ficantly lower (p < 0.05) than that for the arteries (11 nmol/L). Alth ough tamoxifen caused no inhibition of responses induced by high potas sium chloride (80 mmol/L), responses induced by low potassium chloride (20 mmol/L) were inhibited by 40% to 50% in both the myometrium and a rteries. Glibenclamide reversed the inhibition by tamoxifen of spontan eous myometrial activity. CONCLUSIONS: Tamoxifen is a highly potent in hibitor of the contractile activity of the human nonpregnant myometriu m and uterine arteries. It is suggested that tamoxifen could have stro ng potential in the treatment of dysmenorrhea.