Uterotropic effects of dietary equol administration in ovariectomized Sprague-Dawley rats.

AIM: The aim of the present study was to evaluate the uterotropic effects of the administration of dietary equol, a metabolite of soy-derived daidzein or formononetin present in red clover, in an ovariectomized rat model of menopause. METHOD: Two doses of racemic equol were used (50 mg/kg of chow and 400 mg/kg of chow) and the results were compared with two doses of estradiol-3 benzoate (E2B) (4.3 mg/kg of chow and 17.3 mg/kg of chow). After 3 months, animals were sacrificed and the uteri were removed, weighed and paraffin-embedded for morphometrical and immunohistochemical evaluation. The expression of selected uterine estrogen-responsive genes was also measured using real-time reverse transcription-polymerase chain reaction. RESULTS: Compared to controls, uterine weights in animals treated with high-dose equol were significantly higher, presented histologic features of mild estrogenic stimulation and had greater epithelial height and thickness of the uterine stroma and myometrium. Staining for the presence of the proliferating cell nuclear antigen (PCNA) also showed a greater prevalence of the PCNA-positive cells in the uterine stroma in animals treated with high-dose equol. Conversely, the percentage of PCNA-positive cells in the uterine epithelium was lower compared to the controls. Dietary high-dose equol treatment also increased significantly levels of uterine insulin-like growth factor 1, progesterone receptor and complement protein 3 mRNA. Although statistically significant, all these effects were, however, lower in magnitude compared to the effects of low- and high-dose E2B treatment. Low-dose equol did not have any effects on the above-studied parameters. CONCLUSION: Long-term high-dose dietary equol administration to ovariectomized rats exerts uterotropic effects at the cellular and molecular level which question the safety of uncontrolled and unlimited consumption of soy or red clover supplements by postmenopausal women with intact uteri.

Treatment of narcolepsy-cataplexy syndrome with the new selective and reversible MAO-A inhibitor brofaromine-a pilot study.

Eighteen narcoleptic patients were treated in a single-blind study with brofaromine, a new selective and reversible MAO-A-inhibitor. After a drug-free period of seven days, brofaromine was administered for two weeks. Patients were treated with 75 mg brofaromine for the first week and with 150 mg brofaromine for the second week of the study. After an adaptation night nocturnal sleep EEGs were recorded under placebo before brofaromine was given, one week later under 75 mg, and another week later under 150 mg brofaromine. Excessive daytime sleepiness (EDS) was evaluated under placebo at the beginning of the study, under 75 mg at the end of the first week, and under 150 mg brofaromine at the end of the second week by means of the Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT). The number of cataplexies was protocolled by the patients. Compared to placebo the administration of 150 mg brofaromine led to a significant increase of sleep latency in the MLST as well as in the MWT. REM sleep was significantly suppressed in the nocturnal sleep EEG, in the MSLT and in the MWT. The number of cataplexies protocolled by the patient was significantly decreased under 150 mg of brofaromine compared to placebo. Improvement of vigilance and cataplexy occurred in dose-dependent manner. No serious side effects were observed. The results of the present single-blind study indicate that brofaromine seems to be a well-tolerated and effective drug for the treatment of excessive daytime sleepiness and cataplexy in narcoleptic patients.