THE EFFECT OF EXTENDED GONADOTROPIN-RELEASING-HORMONE AGONIST ADMINISTRATION ON UTERINE LEIOMYOMA HISTOPATHOLOGY

Although gonadotropin-releasing hormone agonists (GnRHa) reduce uterin e and myomatous volume, previous reports have revealed contradictory c onclusions about the occurrence of ensuing adverse histopathologic eff ects. We undertook a study to examine the association between duration of GnRHa treatment and histopathologic changes in leiomyomas. A retro spective cohort analysis was performed of 98 patients with uterine lei omyomas treated surgically with myomectomy or hysterectomy. A control group received no preoperative GnRHa treatment (group I, n = 46), grou p II (n = 32) received short-term treatment (1-4 months), and group II I received extended treatment (1 patient for 5 months and 19 patients for 6 months). Patients ranged in age from 26 to 53 years, with a medi an of 35 years. Pretreatment uterine size ranged from 12 to 24 weeks ( median 18 weeks). No differences were identified between groups with r egard to mitosis, severe atypia, vascularity, and necrosis. Patients i n the treatment groups demonstrated an increase in mild atypia that pe rsisted when subject to multiple logistic regression analysis controll ing for age (group II, p < 0.015, adjusted odds ratio 7.9, 95% confide nce interval, CI, 1.5-42.9, group III, p < 0.001, adjusted odds ratio 12.8, 95% CI 2.3-72.1. Although we found an increase in mild atypia in leiomyomas exposed to an estrogen-poor environment for more than 1 mo nth, this finding may not be widely reproducible. More significantly, there was no increase in severe atypia or any other deleterious histop athologic change. We have demonstrated in a large cohort that extended agonist therapy does not significantly alter leiomyoma histopathology . Any pathologic change occurring in extirpated leiomyoma specimens fo llowing GnRHa cannot be ascribed to the therapeutic agent and warrants definitive therapeutic intervention.