The histopathology of uterine leiomyomas following treatment with gonadotropin-releasing hormone analogues

Abstract

Gonadotropin-releasing hormone analogues (GnRH agonists) cause pituitary desensitization by downregulation of GnRH receptors, decrease gonadal steroid production, and reduce uterine volume in women with leiomyomas. The purpose of this study was to examine the morphologic changes in uterine leiomyomas associated with GnRH agonist treatment. The study group consisted of 33 patients (mean age, 36.9 years) who presented with infertility, dysmenorrhea, and/or menorrhagia, and who were treated with a GnRH agonist prior to surgery. A control group consisted of 44 premenopausal patients (mean age, 41.5 years) with similar symptomatology who underwent resection of leiomyomas only. In neither group was there any history of recent pregnancy, uterine surgery, or hormone replacement therapy. Microscopic review of all cases was performed without knowledge of the therapeutic history. No differences with respect to mitotic activity, fibrosis, edema, or vascular changes were detected. There is a suggestion that leiomyomas subjected to preoperative GnRH agonist treatment showed increased cellularity ( P = .04); necrosis ( P < .001) was associated with preoperative GnRH agonist treatment. The reduction of leiomyoma size during GnRH agonist therapy may be due to both ischemic injury and cellular atrophy. Although necrosis of leiomyomas is associated with GnRH agonist treatment, the lack of significant pleomorphism or mitotic activity distinguishes these altered leiomyomas from leiomyosarcomas.