Cl. Walker et al., Preclinical evidence for therapeutic efficacy of selective estrogen receptor modulators for uterine leiomyoma, J SOC GYN I, 7(4), 2000, pp. 249-256
Citations number
37
Categorie Soggetti
Reproductive Medicine
Journal title
JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION
OBJECTIVE: Uterine leiomyoma are the most common gynecologic neoplasm and a
primary cause of hysterectomy in premenopausal women. Preclinical studies
were conducted in the Eker rat model to investigate the potential efficacy
of selective estrogen receptor modulators (SERMs) as therapeutic agents for
this tumor.
METHODS: Twelve-month-old Eker rats were randomized into five treatment arm
s including tamoxifen, placebo, LY 326315, vehicle, and no treatment. Addit
ional animals received ovariectomy or sham surgery at 4 months of age to de
termine the effect of ovarian ablation on tumor development. The study was
terminated after 2 to 4 months of treatment, and tumor incidence, size, pro
liferative and apoptotic indices were determined. Size and incidence data w
ere subjected to chi-square analysis. One-way analysis of variance and Fish
er's least significant difference tests were used to compare proliferative
and apoptotic indices.
RESULTS: Ovariectomy virtually ablated leiomyoma development, indicating th
at these tumors were dependent on ovarian hormones for growth and developme
nt. Treatment with tamoxifen or raloxifene analog LY 326315 reduced leiomyo
ma incidence by 40-60% and reduced the size of remaining tumors. The effect
of SERMs on leiomyomas was mediated by a decrease in cell proliferation wi
thout a decrease in apoptotic index.
CONCLUSION: SERMs have been shown to be therapeutically efficacious against
breast cancer and to reduce tumor incidence in women at increased risk for
this disease. The present data indicate that therapeutic efficacy may also
be extended to uterine leiomyoma and demonstrate the utility of this anima
l model for preclinical studies to identify new therapeutic modalities. (J
Soc Gynecol Investig 2000;7:249-56) Copyright (C) 2000 by the Society for G
ynecologic Investigation.