SUPPRESSION OF CELL-PROLIFERATION AND INDUCTION OF APOPTOSIS IN UTERINE LEIOMYOMA BY GONADOTROPIN-RELEASING-HORMONE AGONIST (LEUPROLIDE ACETATE)

Cell proliferation and apoptosis in uterine leiomyoma were investigate d during therapy with GnRH agonist (GnRHa). Patients with uterine leio myomas were injected with 3.75 mg GnRHa (depot leuprolide acetate) at intervals of 4 weeks and underwent hysterectomy or myomectomy at the 2 nd, 4th, 8th, 12th, or 16th week of GnRHa therapy. Tissue sections of leiomyomas from these patients and from control patients (control pati ents received no GnRHa therapy) were stained with the Ki-67 antibody o r by an in situ DNA 3'-end labeling method, and numbers of Ki-67 immun ostained cells and DNA 3'-end-labeled cells per cm(2) were examined as indices of cell proliferation and apoptosis, respectively. The number of Ki-67 immunostained cells/cm(2) in leiomyomas at the 2nd week of t he GnRHa therapy was comparable with that of control patients. However , it decreased to a level less than one forth that of control patients at the 4th week, and it remained at similar low levels at the 8th, 12 th, and 16th week. The number of DNA 3'-end-labeled cells/cm(2) in lei omyomas of control patients and in leiomyomas at the 2nd, 8th, 12th, a nd 16th weeks of GnRHa therapy were at low levels but, at the 4th week , was at an extremely high level (about 5 times more than that of cont rol patients. The present results indicate that GnRHa therapy suppress es cell proliferation and causes a transient increase in apoptosis in uterine leiomyomas.