Increases in glucocorticoids are part of healthy female ovarian cycles: a systematic review across vertebrates.

Glucocorticoids (GCs), such as cortisol and corticosterone, are hormones that have been widely linked to stress and thought to inhibit reproductive function. However, this conclusion is largely based on studies that administer exogenous GCs, rather than an understanding of the relationship between natural, endogenous GCs and reproduction. To begin to address this gap in our knowledge, this systematic review aims to characterize endogenous GC patterns across reproductive stages in a range of vertebrates. Specifically, we focused on GC patterns across the ovarian cycle in healthy, sexually mature females across vertebrate taxa. From more than 3000 papers screened, we identified 68 that met our inclusion criteria. We found that GCs show predictable fluctuations across the ovarian cycle, with 73% of the studies reporting a significant change in GCs across stages of the cycle. In the majority of studies, GCs were highest around the time of ovulation. This suggests that increases in GCs might promote or support certain aspects of reproductive function, in contrast to the prevailing dogma that GCs always inhibit reproduction. We discuss evidence that GC peaks around ovulation might stimulate oocyte maturation (either alone or synergistically with luteinizing hormone) and/or regulate inflammatory processes related to follicle rupture. Recognizing that increases in GCs might support aspects of ovarian function across taxa represents a paradigm shift in how we think about the relationship between GCs and reproduction, moving us towards a new realm for understanding reproduction and reproductive failure that, as of yet, remains relatively unexplored.