Effects of raloxifene in a guinea pig model for leiomyomas

• Published in: American journal of obstetrics and gynecology 1998-11, Vol.179 (5), p.1283-1287
• Main Authors: Porter, Kathy B., Tsibris, John C.M., Porter, Gregory W., Fuchs-Young, Robin, Nicosia, Santo V., O’Brien, William F., Spellacy, William N.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Estradiol - blood; Estrogen Antagonists - blood; Estrogen Antagonists - therapeutic use; estrogens; Female; Genital system. Reproduction; Guinea Pigs; Leiomyoma - blood; Leiomyoma - chemically induced; Leiomyoma - diagnostic imaging; Leiomyoma - drug therapy; Leiomyomas; Medical sciences; Ovariectomy; Pharmacology. Drug treatments; Piperidines - blood; Piperidines - therapeutic use; raloxifene; Raloxifene Hydrochloride; selective estrogen receptor modulators; Ultrasonography; Uterine Neoplasms - blood; Uterine Neoplasms - chemically induced; Uterine Neoplasms - diagnostic imaging; Uterine Neoplasms - drug therapy
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/S0002-9378(98)70148-6

Objective: Chronic exposure of oophorectomized guinea pigs to 17β-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. Study Design: 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. (Am J Obstet Gynecol 1998;179:1283-7.)