The use of dexamethasone in animals: implication for fertility, pregnancy and extrapolation of the animal data to humans

Abstract

Exposure to dexamethasone causes numerous changes in various biological systems including the reproductive system and this has huge implication on fertility and pregnancy. Maternal dexamethasone administration promotes foetal lung maturation and thermoregulation in premature foetuses. This indication makes dexamethasone a drug of choice in maternal and neonatal human and veterinary health care. In addition, dexamethasone is widely used in human and veterinary medicine as potent anti-inflammatory, immunosuppressive and analgesic drug in all age categories. Although the safety profile of short term dexamethasone treatment has been established, there has been growing concern about the long term effects of dexamethasone therapy and its implication on fertility and pregnancy in animals and humans. Most of the indications or uses in humans are extrapolated from animal data. This necessitates the need to provide review updates of current literature on dexamethasone use in humans and animals as there are many intrinsic differences between humans and animals. The review provides an overview of dexamethasone uses, its merits and demerits on animal pregnancy and fertility and implication on extrapolation of the animal data to humans. The review is based on a comprehensive literature search of relevant materials between 1969 and 2016 as well as authors’ personal manuscript/abstract files and citations of known references and discussed according to the multidisciplinary clinical experience of the authors. Although low-dose dexamethasone treatment has been used in veterinary and human clinics for many years and produced no severe effect on vital functions, repetitive high dose or long-term therapy may be associated with more serious sequelae on fertility and pregnancy. While no animal truly recapitulates human pregnancy and fertility, it is recommended that results from animal data be subjected to rigorous preclinical pharmacokinetic scaling processes to justify possible extrapolation to humans.

Keywords: Animals, Dexamethasone, Fertility, Humans, Pregnancy