Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis

Objective: To evaluate uterine contractility, oxytocin receptor (OTR) expression in myometrial smooth muscle cells (MSMCs) derived from uterine tissues from women with and without adenomyosis correlate OTR expression with uterine contractility and dysmenorrhea severity, and see whether trichostatin A (TSA) and andrographolide inhibit OTR expression. Design: Laboratory study using human tissues. Setting: Academic hospital. Patient(s): Twenty patients (cases) with histologically confirmed adenomyosis and 10 (controls) with leiomyomas, cervical dysplasia, and cancer but no adenomyosis or endometriosis. Intervention(s): Dysmenorrhea severity was scored by Visual Analog Scale. Uterine tissue samples were collected during hysterectomy. Myometrial smooth muscle cells derived from tissue samples were cultured and OTR protein levels were measured. The effect of TSA (0.5 or 1 mu M) and andrographolide (15 or 30 mu M) on OTR expression was evaluated. Main Outcome Measure(s): Visual Analog Scale scores, and contractile amplitude and frequency. The OTR protein levels in MSMCs were quantified by Western blot analysis. Result(s): The contractile amplitude and OTR expression levels were significantly higher in cases than in controls. Dysmenorrhea Visual Analog Scale scores correlated positively with contractile amplitude and OTR expression level. Both TSA and andrographolide dose-dependently inhibit OTR expression in MSMC. Conclusion(s): Oxytocin receptor overexpression in MSMCs may be responsible for increased uterine contractility and adenomyosis-associated dysmenorrhea. Both histone deacetylase inhibitors and andrographolide are therapeutically promising. (Fertil Steril (R) 2013;99:231-40. (C) 2013 by American Society for Reproductive Medicine.)