Hyperprolactinemia is caused by pituitary tumors and pharmacologic or pathologic interruption of dopaminergic pathways. Elevated prolactin levels can also cause endocrine dysfunction at multiple levels of the reproductive cascade including hypogonadotropic hypogonadism, irregular menstruation, erectile dysfunction, infertility and bone loss. Recent data suggests that hyperprolactinemia causes reduced kisspeptin expression, which then leads to reductions in GnRH secretion, and hypogonadotropic hypogonadism. In mice, peripheral kisspeptin administration restores GnRH secretion, gonadotropin release, and ovarian cycles. In human patients with hyperprolactinemia (Preliminary Data), exogenous kisspeptin administration also restores gonadotropin secretion. Thus, this application explores the use of exogenous pulsatile kisspeptin as a therapeutic alternative for patients with hyperprolactemia who are intolerant to current therapies.
Hyperprolactinemia is one of the most common hypothalamic pituitary problems in clinical endocrinology and leads to irregular menstrual cycles, infertility and bone loss. These effects are thought to be due to suppression of the hypothalamic hormone kisspeptin. This application explores the use of exogenous pulsatile kisspeptin administration as a therapeutic alternative for patients with hyperprolactemia who are intolerant to current therapies.