Emerging wastewater contaminant metformin causes intersex and reduced fecundity in fish

Nicholas J. Niemuth, Rebecca D. Klaper


  • Fish were exposed to metformin at concentrations relevant to wastewater effluent.
  • Exposure from early life stages to adulthood caused intersex in male fish.
  • Exposure caused a reduction in fecundity and in overall size of male fish.
  • Results suggest that metformin is a potential endocrine disruptor in the environment.
  • Metformin may be another cause of intersex fish seen globally.


The occurrence of intersex fish, where male reproductive tissues show evidence of feminization, have been found in freshwater systems around the world, indicating the potential for significant endocrine disruption across species in the ecosystem. Estrogens from birth control medications in wastewater treatment plant effluent have been cited as the likely cause, but research has shown that endocrine disruption is not solely predictable based on hormone receptor interactions. Many other non-hormone pharmaceuticals are found in effluent at concentrations orders of magnitude higher than estrogens, yet there is little data indicating the impacts of these other medications. The widely prescribed anti-diabetic metformin is among the most abundant of pharmaceuticals found in effluent and is structurally dissimilar from hormones. However, we show here that exposing fathead minnows (Pimephales promelas) to a concentration of metformin found in wastewater effluent causes the development of intersex gonads in males, reduced size of treated male fish, and reduction in fecundity for treated pairs. Our results demonstrate that metformin acts as an endocrine disruptor at environmentally relevant concentrations. The complete study can be found at: