Dydrogesterone increases allopregnanolone in selected brain areas and in serum of female rats

ObjectiveTo investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid allopregnanolone and the opioid β-endorphin.DesignExperimental study on animal model.SettingAcademic research environment.Animal(s)72 Wistar female rats.Intervention(s)One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day).Main Outcome Measure(s)Allopregnanolone and β-endorphin, assessed in different brain areas and in circulation.Result(s)Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and reduced β-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of β-endorphin induced by E2V.Conclusion(s)Dydrogesterone interacts with allopregnanolone levels (less with β-endorphin), and it can be considered important modulator of the neuroendocrine function.