The gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate depot was used as a biologic probe to investigate the possible roles of insulin-like growth factors (IGFs) I and II in fibroid growth. The secretion of IGF-I and IGF-II by explant cultures of fibroids and myometria from women treated with a GnRH-a was compared with that of tissue obtained from placebo-treated controls. Patients were randomized to receive either leuprolide 3.75 mg every 28 days (N = 9) or placebo injections (N = 8) before myomectomy. Fresh tissue was diced into 2-mm3 explants and cultures were established in serum-free media. The media were assayed for IGF-I, IGF-II, and total protein. Patients treated with GnRH-a demonstrated a 34% reduction in uterine volume, whereas placebo-treated patients exhibited no change. The secretion of IGF-I and IGF-II by fibroid explants obtained from women treated with the GnRH-a was significantly less than that in tissue obtained from placebo-treated controls (P less than .01 and P less than or equal to .05, respectively). Similarly, the secretion of IGF-I and IGF-II by myometrial explants was significantly less in tissue obtained from women treated with GnRH-a (P less than .0001 for both IGF-I and IGF-II). Protein secretion by fibroid tissue obtained from women treated with GnRH-a was not significantly different when compared with tissue from placebo-treated controls. In conclusion, fibroids and myometria from women pretreated with the GnRH-a secreted significantly less IGF-I and IGF-II than did tissue obtained from placebo-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)