Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies

Abstract

<b><i>Objective:</i></b> The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. <b><i>Design:</i></b> This was a controlled and prospective ex vivo study. <b><i>Setting:</i></b> The work was conducted as a collaboration between 4 academic departments. <b><i>Materials and Methods:</i></b> Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; <i>N</i> = 15), and ovarian (<i>N</i> = 15), endometrial (<i>N</i> = 15), synchronous ovarian-endometrial (<i>N</i> = 3), and cervical cancer (<i>N</i> = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. <b><i>Results:</i></b> Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all <i>p</i> &#x3c; 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both <i>p</i> &#x3c; 0.001). <b><i>Limitations:</i></b> These results require now to be placed into a firm clinical context. <b><i>Conclusions:</i></b> Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.