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.

Key Words:  Apoptosis , Bax , Bcl-2 , leiomyoma , PCNA , raloxifene , SERM