Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment.

In aquatic ecosystems, progesterone (P4) and synthetic progestins (gestagens) originate from excretion by humans and livestock. Synthetic progestins are used for contraception and as P4 for medical treatments as well. Despite significant use, their ecotoxicological implications are poorly understood. Only about 50% of the progestins in use have been analyzed for their environmental occurrence and effects in aquatic organisms. Here we critically summarize concentrations and effects of progestins in aquatic systems. P4 and progestins were mostly detected when analyzed for, and they occurred in the low ng/L range in wastewater and surface water. In animal farm waste and runoff, they reached up to several μg/L. P4 and synthetic progestins act through progesterone receptors but they also interact with other steroid hormone receptors. They act on the hypothalamus-pituitary-gonad axis, lead to oocyte maturation in female and sperm motility in male fish. Additionally, other pathways are affected as well, including the circadian rhythm. Effects of P4, mifepristone and eleven synthetic progestins have been studied in fish and a few compounds in frogs and mussels. Environmental risks may be associated with P4, dydrogesterone and medroxyprogesterone acetate, where transcriptional effects were found at highest environmental levels. Reproductive effects occurred at higher levels. However, norethindrone, levonorgestrel and norgestrel compromised reproduction at environmental (ng/L) concentrations. Thus, some of the progestins are very active endocrine disrupters. This review summarizes the current state of the art and highlights risks for fish. Further research is needed into environmental concentrations and effects of non-investigated progestins, unexplored modes of action, and the activity of mixtures of progestins and other steroids to fully assess their environmental risks.