Gonadotropin-Releasing Hormone Antagonist Combination Therapies for Perimenopausal Uterine Leiomyoma Care

In this clinical perspective, we examine the role of gonadotropin-releasing hormone (GnRH) antagonist combination therapies in the management of uterine leiomyomas during perimenopause, a period marked by hormonal variability and heightened symptom burden. Drawing on mechanistic comparisons, randomized trial data, and long-term safety findings, we review evidence demonstrating that GnRH antagonist combination therapies provide rapid, reversible suppression of gonadotropin secretion without an estrogen flare. This, in turn, results in consistent reductions in heavy menstrual bleeding associated with leiomyomas, management of bulk-related symptoms, and improvement with anemia. We further highlight limitations of conventional hormonal and expectant management strategies during perimenopause and discuss practical considerations for patient selection and monitoring. Collectively, these findings support GnRH antagonist combination therapy as a targeted, time-limited, and well-tolerated treatment option that addresses a critical therapeutic gap for perimenopausal patients with symptomatic uterine leiomyomas.