Antiproliferative and proapoptotic effects of raloxifene on uterine leiomyomas in postmenopausal women.

Objective: To study the cell effects of raloxifene on uterine and leiomyoma tissue in postmenopausal women.

Design: Prospective, randomized, double-blind, placebo-controlled study.

Setting: Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro, Italy.

Patient(s): Forty postmenopausal women affected by uterine leiomyomas and selected for hysterectomy.

Intervention(s): Treatment for three cycles of 28 days with raloxifene at a dose of 180 mg/day orally (raloxifene group) or placebo tablets (3 tablets/day orally) (placebo group).

Main Outcome Measure(s): Uterine and leiomyoma dimensions were measured in each subject at entry and before surgery. On leiomyomas and homologous myometrium the proliferating cell nuclear antigen (PCNA)-positive cells/total cells (PCNA/TC) and the Bcl-2-positive cells/Bax-positive cells (Bcl-2/Bax) ratios (%), as proliferation and apoptotic indexes, respectively, were measured.

Result(s): After treatment, uterine and leiomyoma sizes were significantly changed in comparison with baseline and the placebo group. PCNA/TC and Bcl-2/Bax ratios were significantly higher in leiomyomas than in homologous myometrium. A significant difference was detected in PCNA/TC between the myometrium of the raloxifene and control groups, whereas no difference was observed in the Bcl-2/Bax ratio. A significant difference in PCNA/TC and Bcl-2/Bax ratios was detected in leiomyoma tissue between the raloxifene group and controls.

Conclusion(s): In postmenopausal women, raloxifene administration reduces uterine leiomyomas by exerting a cell antiproliferative and proapoptotic action.