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Here, we report the role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood. We provide evidence that the effects and mechanisms underlying their actions are still confusing due to the use of different estrogens and progestins as well as different doses, duration of exposure, route of administration, baseline hormonal status and age of treated women. We also discuss the emerging issue concerning the relevant increase of these substances in the environment, able to deeply affect aquatic wildlife as well as to exert a possible influence in humans, which may be exposed to these compounds via contaminated drinking water and seafood. Finally, we report literature data showing the neurobiological action of progestins and in particular their importance during neurodegenerative events. 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