The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity

Abstract

The objective of this study was to correlate, during 12 weeks of therapy with gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the hemodynamic changes on the uterine artery and the leiomyometrial supplying vessels. Twenty-three premenopausal women with clinically diagnosed uterine leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma volumes and blood flow characteristics of the main uterine artery and leiomyoma supplying vessels-resistance index (RI), pulsatility index (PI) and peak-systolic velocity, obtained by transvaginal color Doppler sonography-were compared with treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy. The first event in the chronological response to the GnRH-a therapy was a statistically significant increase in RI and PI values for major leiomyoma vessels, observed at the end of the 4th week (p < 0.05), which increased significantly after 8 and 12 weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct correlation with a significant decrease of estradiol levels after 4, 8 and 12 weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease of blood flow in the leiomyometrial vessels was followed by a significant decrease of the main uterine artery blood flow after 8 weeks and uterine and leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy. We concluded that a significant increase in leiomyometrial vessels RI and PI values, which was found 4 weeks after the first dose of GnRH-a, but without major leiomyoma volume decrease, emphasizes that the first significant effect of GnRH therapy in the process of uterine and leiomyoma volume shrinkage is the reduction of leiomyometrial rather than uterine blood flow. This effect is followed by a considerable reduction of uterine vascularity and a significant decrease of uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate therapy duration.

Gonadotropin-releasing hormone agonist pretreatment did not decrease postoperative adhesion formation after abdominal myomectomy in a randomized control trial

“…This is consistent with prior reports that have demonstrated that estrogen and progesterone both promote angiogeneisis and growth factor production in female reproductive tissues (4,5) and that pelvic adhesions have estrogen and progesterone receptors (6). Additionally, estrogen deprivation causes an decrease in uterine blood flow, (7,8), and hypoestrogenism causes fibroids to shrink by approximately 40% after 3 months of GnRH-a therapy; thus, incision size would be expected to be smaller (8)(9)(10). Changes in the coagulation system, including plasminogen activator, plasminogen activator inhibitor, and matrix metalloproteinase, may also affect the mechanism of adhesion formation (11).…”

Role of GnRH agonists prior to endoscopic surgical treatment of fibroids

“…Similar conclusions have also been reported by other authors [41,42,43]. In a prospective study using transvaginal color doppler sonography, Aleem et al [44] studied the hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity. The arterial resistance first increased in fibroid arteries in the fourth week of therapy.…”

A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata

“…A decrease in uterine blood flow was observed elsewhere in patients with leiomyomata during treatment with GnRH-a, and this effect has been proposed as an early mechanism leading to the reduction in leiomyoma and uterine volumes (32). Inhibitory effects on uterine blood flow in patients with leiomyomata were also described after treatment with the P antagonist mifepristone (33).…”