Human uterine leiomyomata express higher levels of peroxisome proliferator-activated receptor gamma, retinoid X receptor alpha, and all-trans retinoic acid than myometrium.

Uterine leiomyomata are the main indication for a hysterectomy in the United States and occur in 25% of women >35 years. Because uterine leiomyomata can form when ovariectomized guinea pigs are exposed to estradiol and retinoic acids, we tested whether human leiomyomata had high levels of retinoic acids and related nuclear receptors. Compared with normal human myometrium, leiomyomata had 3- to 5-fold higher levels of peroxisome proliferator-activated receptor gamma (PPARgamma), retinoid X receptor alpha proteins, and all-trans retinoic acid, but only during the follicular phase of the menstrual cycle. 9-cis Retinoic acid was undetectable in either leiomyomata or myometrium. PPARgamma mRNA levels were lower in leiomyomata than myometrium, but only during the luteal phase of the cycle. A PPARgamma agonist, troglitazone, was given to guinea pigs along with estradiol and all-trans retinoic acid and produced the largest leiomyomata seen to date in this model. By contrast, no tumors formed when troglitazone was given alone or with estradiol or when troglitazone was given with estradiol and 9-cis retinoic acid. New therapies for human leiomyomata may emerge by combining antagonists for PPARgamma and retinoid X receptor alpha with selective estrogen receptor modulators.

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. 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.

Patient-administered outpatient intravaginal prostaglandin E2 suppositories in post-date pregnancies: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To shorten post-date pregnancies in a safe, effective manner by outpatient acceleration of cervical ripening. METHODS: Eighty patients with uncomplicated pregnancies at or beyond 41 weeks' gestation and a cervical Bishop score less than 9 were randomized to daily self-administered, 2-mg intravaginal prostaglandin E2 (PGE2) or placebo suppositories. Each followed a standard post-date antepartum surveillance protocol. Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9, antepartum testing was nonreassuring, exclusion criteria were fulfilled, or if the gestational age reached 44 weeks. RESULTS: Fewer suppositories were used in the PGE2 group (four versus seven; P = .006), resulting in earlier gestational age on admission (295 versus 297 days; P = .021) and lower antepartum testing charges ($476.97 versus $647.29; P = .001). Labor and delivery time was significantly decreased in nulliparas (10.7 +/- 5.1 versus 15.3 +/- 7.6 hours; P = .035). CONCLUSIONS: Daily low-dose, patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post-date pregnancies by reducing the time to achieve a favorable cervix, the need for antepartum testing, and, potentially, post-date-related complications.