Effects of raloxifene in a guinea pig model for leiomyomas.
OBJECTIVE
Chronic exposure of oophorectomized guinea pigs to 17beta-estradiol causes leiomyoma formation. Our aims were to determine whether these leiomyomas can become estradiol independent after exposure to estradiol and if raloxifene inhibits leiomyoma growth when given concomitantly with estradiol.


METHODS
To induce leiomyoma development, 6 oophorectomized animals received two estradiol implants for 140 days. Next, the estradiol implants were replaced with empty implants in 3 animals, whereas the other 3 received 2 new estradiol implants and raloxifene given per os 10 mg/kg per day for 60 days. Tumor size was monitored biweekly by ultrasonography.


RESULTS
On estradiol removal, abdominal wall leiomyomas regressed within 15 to 30 days; when estradiol implants were reintroduced, leiomyomas redeveloped. Within 30 days on raloxifene, all abdominal leiomyomas (n = 9) regressed as determined by ultrasonography and verified at laparotomy. Serum raloxifene and estradiol levels were 432 +/- 46 pg/mL and 78 +/- 13 pg/mL (mean +/- SEM, n = 3), respectively, after 60 days of treatment.


CONCLUSIONS
Leiomyomas did not become estradiol independent, even after long exposure to estradiol; ultrasonography allowed frequent, noninvasive assessment of leiomyoma size, and raloxifene rapidly regressed leiomyomas in this animal model.
Porter
K B
KB
Departments of Obstetrics and Gynecology, Biochemistry and Molecular Biology, and Pathology, University of South Florida College of Medicine, Tampa, Florida, USA.
Tsibris
J C
JC
Porter
G W
GW
Fuchs-Young
R
R
Nicosia
S V
SV
O'Brien
W F
WF
Spellacy
W N
WN
D000818:Animals; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D007889:Leiomyoma / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010052:Ovariectomy; D010880:Piperidines / Q000097:blood / Q000627:therapeutic use*; D020849:Raloxifene Hydrochloride; D014463:Ultrasonography; D014594:Uterine Neoplasms / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*
D004965:Estrogen Antagonists; D010880:Piperidines; D020849:Raloxifene Hydrochloride; D004958:Estradiol