Raloxifene enhanced the efficacy of GnRHa treatment in uterine leiomyomas in premenopausal women

OBJECTIVE To determine if there is any enhancement of e⁄cacy with the addition of raloxifene to gonadotropin-releasing hormone agonist (GnRHa) treatment for uterine leiomyomas in premenopausal women. DESIGN Multicentre, randomized, double-blind (subject and assessor), placebo-controlled trial. Allocation was by computer-generated list. SETTING Three university hospitals in Italy. SUBJECTS One hundred premenopausal women, mean age 49 years, who requested medical treatment for symptomatic uterine leiomyomas.Women with low bone mineral density (BMD) or very low or high body mass index were excluded. Nine randomized women (9%) did not complete the study, a similar proportion in each group. INTERVENTION All women received leuprolide acetate depot 3.75 mg every 28 days for six cycles. Fifty women were randomized to receive, in addition, oral raloxifene 60 mg and another 50 women to receive placebo, one tablet daily for six cycles. Uterine and leiomyoma volumes were measured by transvaginal ultrasonography at baseline and after six cycles of treatment. MAIN OUTCOME MEASURES Change in total uterine, leiomyoma, and non-leiomyoma uterine volumes and leiomyoma-related symptoms, frequency of vaginal bleeding and hot £ushes. MAIN RESULTS On average, women in both groups had signi¢cant reductions from baseline in total uterine, leiomyoma, and non-leiomyoma uterine volumes. After six cycles of treatment, the total uterine volume decreased from baseline by a mean (7SD) 58711%* in the raloxifene group, compared to 49713%* in the placebo group (po0.001, absolute treatment e¡ect [ATE] 9%, 95% CI 4^14w). Leiomyoma volume decreased by 7078%* and 39711%*, respectively (po0.0001, ATE 31%, CI 27^35)w. The mean decrease in non leiomyoma uterine volume was similar in the two groups (37^39%w). The prevalence and severity of leiomyoma-related symptoms (menorrhagia, pelvic pressure, pelvic pain, urinary frequency, and constipation) were signi¢cantly reduced in both groups, with no signi¢cant di¡erence between groups. Vaginal bleeding was experienced by fewer than 20% of women in both groups, from the third cycle on. Raloxifene did not prevent the occurrence of hot fushes (mean 3^6 per day throughout the treatment period in both groups). CONCLUSION The addition of raloxifene to long-term GnRHa treatment for uterine leiomyomas in premenopausal women resulted in greater reductions in leiomyoma and total uterine volumes, but similar reductions in symptoms