Identification of drug-induced hyper- or hypoprolactinemia in the female rat based on general and reproductive toxicity study parameters.

Observations associated with drug-induced hyper- or hypoprolactinemia in rat toxicology studies may be similar and include increased ovarian weight due to increased presence of corpora lutea. Hyperprolactinemia may be distinguished if mammary gland hyperplasia with secretion and/or vaginal mucification is observed. Reproductive toxicity study endpoints can differentiate hyper- from hypoprolactinemia based on their differential effects on estrous cycles, mating, and fertility. Although the manifestations of hyper- and hypoprolactinemia in rats generally differ from that in humans, mechanisms of drug-related changes in prolactin synthesis/release can be conserved across species and pathologically increased or decreased prolactin levels may compromise some aspect of reproductive function in all species.