Treatment with a gonadotropin-releasing hormone (GnRH) agonist reduces the total uterine volume, with the greatest change occurring in the first eight weeks of therapy. The uterine changes in response to GnRH agonist therapy have been attributed to uterine atrophy, vaso-constriction and myometrial activity. GnRH agonists have also been shown to affect the blood flow through the uterine artery. Weeks and associates assessed changes in uterine volume and in uterine artery pulsatility index in response to GnRH agonist therapy in 51 women scheduled to have a hysterectomy for uterine bleeding unrelated to fibroid tumors.
Patients in this double-blind, placebo-controlled study were randomized to receive either leuprolide or placebo for eight weeks. Vaginal ultrasonography was performed before and after treatment to evaluate changes in uterine size and uterine artery pulsatility. Color-flow Doppler imaging was used to quantify the blood flow to the uterus through the uterine artery. The pulsatility index and resistance index represent the ratios of maximum and minimum Doppler shift as the blood flows through the artery. Serum estrogen levels were also determined, at baseline and after eight weeks of treatment. Complete data were available in 43 of the 51 women.
The estradiol level dropped profoundly in response to GnRH agonist therapy; no change occurred in the placebo group. Following active drug treatment, uterine volume decreased a mean of 34 percent, a statistically significant change. The mean change in uterine volume in the placebo group was not significant. The degree of uterine shrinkage with GnRH agonist therapy was negatively correlated with initial uterine volume.
After leuprolide therapy, the pulsatility index value increased significantly by 20 percent; no significant change occurred in the placebo group. The fall in estradiol levels correlated with the increase in vascular bed resistance as indicated by the pulsatility index. A direct correlation between estradiol levels and pulsatility was seen: the greater the fall in the serum estradiol concentration, the greater the increase in the pulsatility index. The presence of adenomyosis had no effect on the uterine artery Doppler results.
The authors conclude that treatment with a GnRH agonist leads to uterine shrinkage and an increase in the uterine artery pulsatility index even in the absence of uterine fibroids. The ability to reduce the volume of the uterus in women who are candidates for hysterectomy may become increasingly important as physicians move to less invasive methods of performing a hysterectomy in order to improve postoperative outcome.