A clinical trial of the effects of tibolone administered with gonadotropin-releasing hormone analogues for the treatment of uterine leiomyomata

Abstract

Objective: To evaluate the effects of tibolone therapy in association with GnRH-a on uterine leiomyomata, on climacteric-like symptoms, on bone metabolism, and on the lipid profile. Design: A prospective, randomized, double-blind, placebo-controlled, clinical trial. Setting: Department of Gynecology and Obstetrics, University of Naples “Federico II,” Naples, Italy. Patient(s): Fifty women with symptomatic uterine leiomyomata. Intervention(s): Six months of treatment with leuprolide acetate (3.75 mg every 28 days IM) combined with daily placebo tablets (group A) or with 2.5-mg of tibolone per os (group B). Main Outcome Measure(s): Uterine and uterine leiomyomata sizes, lumbar spine bone mineral density, biochemical markers of bone metabolism, lipid profile, and myoma-related symptoms were measured at baseline and after 6 months of treatment. Daily symptom diary in which hot flushes and vaginal bleeding episodes were recorded. Result(s): No differences between the 2 groups in uterine and uterine leiomyomata size and myoma-related symptoms were detected. After 6 months of treatment, there were statistically significant changes from baseline in bone mineral density and in biochemical markers of bone metabolism in group A but not in group B. Vasomotor symptoms were significantly lower in group B than in group A. There was a statistically significant increase ( P<.01) in serum total cholesterol, high-density lipoprotein cholesterol, and triglycerides in group A after 6 months of treatment in comparison with baseline values. The difference in serum total cholesterol and triglyceride levels after 6 months of treatment in group B was not statistically significant in comparison with baseline values, but was statistically significant in comparison with group A values ( P<.01). In group B, levels of high-density lipoprotein cholesterol were significantly lower after 6 months of therapy in comparison with baseline values and in comparison with group A values ( P<.01). There were no statistically significant changes at baseline and after 6 months of treatment in the level of low-density lipoprotein cholesterol in either group. Conclusion(s): Administration of tibolone in association with GnRH-a reduces vasomotor symptoms and prevents bone loss, without compromising the therapeutic efficacy of GnRH-a alone.