Rapid regression of uterine leiomyomas in response to daily administration of gonadotropin-releasing hormone antagonist.
OBJECTIVE
The efficacy of acute and sustained pituitary gonadotropin down-regulation by the Nal-Glu GnRH antagonist (Nal-Glu) was evaluated in the treatment of uterine leiomyomas.


METHODS
Prospective, open clinical trial.


METHODS
Seven normally cycling women with symptomatic leiomyomas.


METHODS
Nal-Glu (50 micrograms/kg per day) was administered subcutaneously for 3 months.


METHODS
Baseline ultrasound examinations were obtained and repeated monthly throughout treatment. Each leiomyoma was mapped and measured in three dimensions. Blood samples were drawn daily for 7 days, weekly for 4 weeks, and monthly for the remaining 2 months.


RESULTS
Mean leiomyoma size decreased 52.8 +/- 7.3% (means +/- SD) after 1 month of therapy and remained unchanged for the remainder of the study. Serum levels of E2 (35.9 +/- 11.8 to 9.3 +/- 0.8 pg/mL, 131.7 +/- 43.3 to 34.0 +/- 1.4 pmol/L), estrone (37.3 +/- 7.5 to 13.0 +/- 2.5 pg/mL, 138.1 +/- 27.7 to 48.1 +/- 9.1 pmol/L), and P (1.6 +/- 1.1 to 0.3 +/- 0.01 ng/mL, 5.0 +/- 3.6 to 0.9 +/- 0.04 nmol/L) declined rapidly (within 48 hours) and remained suppressed throughout treatment. Serum LH, FSH, androstenedione, T, and DHEA levels did not change significantly. In two subjects who did not have surgical removal, leiomyomas grew to original size within the 1st month off drug. Six patients remained amenorrheic and the other subject spotted during the last 2 months of therapy.


CONCLUSIONS
Continuous treatment with Nal-Glu induces immediate and sustained pituitary-gonadal down-regulation that results in regression in leiomyoma size. By circumventing GnRH agonist-induced pituitary-ovarian up-regulation, GnRH antagonists may prove to be superior tools in the medical management of leiomyomas.
Kettel
L M
LM
Department of Reproductive Medicine, University of California.
Murphy
A A
AA
Morales
A J
AJ
Rivier
J
J
Vale
W
W
Yen
S S
SS
D000328:Adult; D005260:Female; D005483:Flushing / Q000139:chemically induced; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008598:Menstruation / Q000187:drug effects; D008875:Middle Aged; D011446:Prospective Studies; D014463:Ultrasonography; D014594:Uterine Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*
C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone