Histology of leiomyomata in patients treated with leuprolide acetate

This study examined the histologic changes associated with administration of leuprolide acetate, a gonadotropin-releasing hormone agonist, in 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 controls. Tissue samples of leiomyomata (four to 10 slides per patient) were examined "blinded" by two pathologists and evaluated for cellularity, edema, myxoid change, hyalinization, fibrosis, inflammation, infarction, 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 characteristic. Cellularity, hyalinization, and fibrosis were graded as 1(+) versus 2(+); all other characteristics were graded as present or absent. The analysis showed that leuprolide acetate-treated leiomyomata had significantly increased hyalinization (p < 0.005) and decreased cellularity (p < 0.10) as compared with controls; there was also thickening of blood vessel walls with narrowing of the lumen (p < 0.01). A subgroup of leuprolide acetate-treated patients categorized as clinical responders (having > 30% reduction in tumor size) more frequently had thickening of vessel walls (p < 0.05) and vascular thrombosis (p < 0.10) than did nonresponders. Our data suggest that a leuprolide acetate-induced hypoestrogenic state may cause vasoconstriction, thickening of blood vessel walls, and thrombosis, leading to ischemia, hyalinization, and atrophy of the leiomyoma.