Prenatal exposure to progestins: Impact on neurodevelopment of the child

Abstract Studies of psychiatric effects of progestins on in utero exposed children’s central nervous system (CNS) are scarce. Psychoses such as schizophrenia and bipolarity were described for in utero exposed children to progestins in a French cohort. Psychiatric disorders observed in these patients were compared with CNS disorders that appeared after in utero exposure to synthetic estrogens (DES, EE): no difference was noted. Molecular genomic and epigenomic studies of the estrogen mechanism of action demonstrated that psychosis is in close correlation with specific methylomic modifications that could impact neurodevelopment and neuroplasticity, an epigenetic mechanism. Evidence of psychic disorders on DES daughters analyzed from another French cohort confirms these results. Progestin may also induce autism spectrum disorders by means of an epigenetic mechanism: after animal (rat) study showing a hypermethylation (an epigenetic alteration) of the ERβ receptor genes, an epidemiological study on a large Chinese population confirmed these works. Moreover, a physicochemical study of the amniotic fluid in a male Danish cohort demonstrated that prenatal excess of estrogens contributes to autism to a greater degree than do other prenatal sex steroids. For the protection of future generations, pregnant or not, women should be extremely vigilant about any kind of synthetic hormone therapy.