Veralipride for hot flushes induced by a gonadotropin-releasing hormone agonist: A controlled study

Objectives: To evaluate the efficacy of veralipride, a benzamide derivative, in the treatment of hot flushes induced by GnRH agonists (GnRH- a) and to study peripheral blood mononuclear cell β-endorphin concentrations during drug administration. Design: Randomized, placebo-controlled, double- blind trial. Setting: Academic department of obstetrics and gynecology. Patients: Forty women of mean age 43 ± 5 years who experienced disturbing hot flushes during a 4-month course of tryptorelin depot for myoma-associated menorrhagia. Interventions: Treatment with oral veralipride 100 mg/d (20 subjects) or matching placebo (20 subjects) during the third month of GnRH-a administration. Main Outcome Measures: Modifications of frequency and severity of hot flushes as shown by a 0 to 6-point vasomotor scoring system and variations of β-endorphin levels in peripheral blood mononuclear cells. Results: Two subjects in each group dropped out of the study. The median (range) vasomotor score at the end of the second month of treatment was 4 (3 to 6) in both the veralipride and placebo group. At the end of the third and fourth months the median (range) scores were, respectively, 2 (0 to 6) versus 4 (1 to 6) and 2 (0 to 5) versus 4 (1 to 6). No significant variations in mononuclear cell β-endorphin concentrations were recorded. Serum PRL levels rose from 11.7 ± 5.7 to 132.3 ± 65.0 ng/mL (conversion factor to SI unit, 1.0) during veralipride administration and returned to 10.6 ± 3.7 ng/mL after drug withdrawal. Conclusion: Veralipride reduced vasomotor symptoms induced by a GnRH-a. Transient hyperprolactinemia was the main side effect observed. The mode of action of the drug in GnRH-a-treated patients and possible interactions with endogenous opioid peptides need further elucidation.