Oestrogenic effects of neonatal administration of raloxifene on hypothalamic-pituitary-gonadal axis in male and female rats

Selective oestrogen receptor modulators constitute a family of drugs that a re used increasingly in the management of oestrogen-associated pathology. R aloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxife ne on bone, breast, uterus and serum cholesterol concentrations have been w idely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a seri es of experiments was conducted to analyse the effects of different doses o f raloxifene (50, 100, 250 or 500 mug per rat per day) administered to neon atal rats on days 1-5 of age. Female rats treated with raloxifene showed de creased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal open ing, decreased body weight, persistent presence of cornified epithelial cel ls in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputia l separation, reduced body weight and hyperprolactinaemia. All these change s resemble those obtained after neonatal administration of oestradiol benzo ate, thus indicating, for the first time, that raloxifene exerts an oestrog enic action on the hypothalamic-pituitary structures controlling reproducti ve function in rats.