HISTOLOGY OF LEIOMYOMATA IN PATIENTS TREATED WITH LEUPROLIDE ACETATE

This study examined the histologic changes associated with administrat ion of leuprolide acetate, a gonadotropin-releasing hormone agonist, i n leiomyomata. Thirty-seven women treated with leuprolide acetate who subsequently underwent myomectomy or hysterectomy were matched by age (+/-3 years), race, and uterine size (+/-2 weeks) with untreated contr ols. Tissue samples of leiomyomata (four to 10 slides per patient) wer e examined ''blinded'' by two pathologists and evaluated for cellulari ty, edema, myxoid change, hyalinization, fibrosis, inflammation, infar ction, and vascular changes (thrombosis, intimal fibrosis, thickening of the vessel wall with narrowing of the lumen, perivascular fibrosis) . A matched case-control analysis was conducted for each morphologic c haracteristic, Cellularity, hyalinization, and fibrosis were graded as 1+ versus 2+; all other characteristics were graded as present or abs ent. The analysis showed that leuprolide acetate-treated leiomyomata h ad significantly increased hyalinization (p < 0.005) and decreased cel lularity (p < 0.10) as compared with controls; there was also thickeni ng of blood vessel walls with narrowing of the lumen (p < 0.01). A sub group of leuprolide acetate-treated patients categorized as clinical r esponders (having >30% reduction in tumor size) more frequently had th ickening of vessel walls (p < 0.05) and vascular thrombosis (p < 0.10) than did nonresponders. Our data suggest that a leuprolide acetate-in duced hypoestrogenic state may cause vasoconstriction, thickening of b lood vessel walls, and thrombosis,leading to ischemia, hyalinization, and atrophy of the leiomyoma.