ganirelix and Uterine-Neoplasms

To assess maximal volume reduction of leiomyomas and uterus and the duration of treatment required to reach these reductions with daily GnRH antagonist treatment.. Prospective, open-label study.. Large teaching hospital in The Netherlands.. Premenopausal women with symptomatic fibroids, who were scheduled for surgery.. Twenty women were treated with daily 2 mg of subcutaneous ganirelix. Prior to the first injection and weekly during treatment, the volume of leiomyomas and the uterus were assessed by ultrasound (USS) and serum hormones were measured. Prior to treatment and when maximal size reduction was observed by USS, the volume of the leiomyomas and the uterus were also assessed by magnetic resonance imaging (MRI).. Leiomyoma and uterine size reduction, time to maximal reduction.. One woman was excluded from the study due to incorrect administration dose of ganirelix. Data on the remaining 19 women (average age 39 years) with subserosal (n= 9), submucosal (n= 7), intramural (n= 10) and transmural (n= 1) leiomyomas were evaluated. Baseline leiomyoma volumes ranged from small (3-4 mL) to large (>1000 mL). The median duration of treatment up to maximal leiomyoma size reduction was 19 days (range 1-65 days). The maximal size reduction in leiomyomas measured by USS was -42.7% (-77.0% to 14.1%) and -29.2% (-62.2% to 35.6%) by MRI. Comparable uterine size reductions of -46.6% (-78.6% to -6.1%) and -25.2% (-63.6% to 28.9%) were observed by USS and MRI. During the first three weeks of treatment, 8 out of 19 women reported adverse events related to the induced hypoestrogenic state. Most of these events resolved within one week after treatment was discontinued.. Daily treatment with 2 mg of ganirelix results in rapid reduction of leiomyoma and uterine volume in premenopausal women with minor side effects. If longer-acting GnRH antagonists become available, pretreatment with GnRH antagonist should be preferred over GnRH agonists prior to surgery.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Injections, Intradermal; Leiomyoma; Magnetic Resonance Imaging; Premenopause; Prospective Studies; Uterine Neoplasms

Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellular synthesis in cultured leiomyoma cells. In this study, we encapsulated the GnRH antagonist ganirelix in PLGA microspheres contained in an alginate scaffold that also supports a leiomyoma ex vivo tissue explant. Microspheres maintained ganirelix concentration stably during six days of culture, inducing significant cell death in 50-55% of tumor cells. Although no changes were observed in the expression of extracellular matrix genes, a decreased expression of the Nuclear Factor of Activated T cells 5, a transcription factor involved in osmotic stress and tumor size. Interestingly, all tumors analyzed experienced apoptosis independently of the original driver mutation. These data indicate that local therapy of ganirelix would induce tumor reduction in a wide range of uterine leiomyomas.

Topics: Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyoma; Uterine Neoplasms