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

Objective: To 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. Design: Experimental study on animal model. Setting: Academic 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. © 2008 American Society for Reproductive Medicine.