AN EVALUATION OF THE EFFECT OF GONADOTROPIN-RELEASING-HORMONE ANALOGSAND MEDROXYPROGESTERONE ACETATE ON UTERINE LEIOMYOMATA VOLUME BY MAGNETIC-RESONANCE-IMAGING - A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL

The purpose of this study was to prospectively compare the effectivene ss of administering medroxyprogesterone acetate (MPA; 20 mg/day) in ei ther the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradio l, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomiz ed into protocol A or B, received either MPA or placebo along with GnR H-a, respectively, and were then crossed over at 12 weeks to placebo o r MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magneti c resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estrad iol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 w eeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume de creased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), b ut did not change in protocol A. After crossover at 12 weeks, the tota l uterine volume of women in protocol A decreased to 74% of the baseli ne (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 we eks, but after cross-over, MPA addition was associated with a signific ant increase in total uterine volume (protocol B) compared to a decrea se in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma vol ume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlatio n with a reversal in the GnRH-a-associated decrease in nonmyomatous ti ssue volume. We conclude that 1) the predominant effect of GnRH-a ther apy on total uterine volume changes in cases of leiomyomata uteri is o n nonmyoma uterine tissue, with less of an influence on myoma volume; 2) MPA appears to reverse the effectiveness of GnRH-a-induced hypoestr ogenism in decreasing nonmyoma volume; and 3) no difference was observ ed with respect to levels of estradiol, gonadotropins, or serum lipids between MPA administration and GnRH-a therapy. Thus, MPA is a subopti mal progestin for concomitant treatment regimens with GnRH-a directed toward reduction of the size of leiomyomata uteri.