Influence of exogenous estrogen receptor ligands on uterine leiomyoma: Evidence from an in vitro/in vivo animal model for uterine fibroids

The remarkable frequency of uterine leiomyoma in the human population calls into question the potential for the participation of environmental factors in tumor etiology. Having been implicated in the dramatic rise in hormone- related cancers in recent years, endocrine disrupters are salient suspects in this pathogenesis, although the mechanism by which they might participat e is unclear. Investigations using the Eker rat model show that uterine lei omyoma may have an enhanced sensitivity to modulation via the estrogen rece ptor. This sensitivity could make these tumors a target for disruption by e xogenous estrogen receptor ligands. Direct evidence for a pathogenic role o f exogenous compounds in leiomyomas is lacking; however, it can be demonstr ated that such diverse agents as organochlorine pesticides, dietary flavono ids, botanical extracts, and therapeutic antiestrogens have either estrogen agonist or antagonist function in myometrial tissues. The use of this mode l will help define the impact of exogenous estrogen receptor modulators on uterine leiomyoma and will permit the evaluation of strategies for therapeu tic intervention.