The effect of extended gonadotropin-releasing hormone agonist administration on uterine leiomyoma histopathology

Although gonadotropin-releasing hormone agonists (GnRHa) reduce uterine and myomatous volume, previous reports have revealed contradictory conclusions about the occurrence of ensuing adverse histopathologic effects. We undertook a study to examine the association between duration of GnRHa treatment and histopathologic changes in leiomyomas. A retrospective cohort analysis was performed of 98 patients with uterine leiomyomas treated surgically with myomectomy or hysterectomy. A control group received no preoperative GnRHa treatment (group I, n = 46), group II (n = 32) received short-term treatment (1-4 months), and group III 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 median of 35 years. Pretreatment uterine size ranged from 12 to 24 weeks (median 18 weeks). No differences were identified between groups with regard to mitosis, severe atypia, vascularity, and necrosis. Patients in the treatment groups demonstrated an increase in mild atypia that persisted when subject to multiple logistic regression analysis controlling for age (group II, p < 0.015, adjusted odds ratio 7.9, 95% confidence 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 month, this finding may not be widely reproducible. More significantly, there was no increase in severe atypia or any other deleterious histopathologic 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 following GnRHa cannot be ascribed to the therapeutic agent and warrants definitive therapeutic intervention.