Il trattamento cronico con etinilestradiolo e levonorgestrel modifica i livelli cerebrali dei neurosteroidi e il comportamento nel ratto

Oral contraceptives (OCs) are among the most widely used drugs in the world and offer many benefits for women's health, such as reduction of the risk of endometrial and ovarian cancer, benign ovarian cysts, and are useful in the control of menstrual irregularities and acne. However, several studies show that OCs induce adverse effects in the central nervous system, such as mood disorders, irritability and decreased sexual desire. We have previously demonstrated that long-term treatment with a combination of ethinylestradiol and levonorgestrel (EE/LNG), two of the compounds more frequently used in OCs in female rats decreases brain concentrations of progesterone and its metabolite allopregnanolone, a positive allosteric modulator of the type A receptor for the gamma-aminobutyric acid (GABA), the most common inhibitory neurotransmitter of the central nervous system, which exerts anxiolytic, anticonvulsant, sedative-hypnotics and neuroprotective effects and is involved in the regulation of social and sexual behavior in female rats. The aim of this research was to assess whether the reduction in the brain concentrations of allopregnanolone induced by EE/LNG treatment altered the behavior of rats. Chronic treatment with EE/LNG induces an anxiety-like behavior in animals, reduces agonistic behavior and sexual motivation, while it does not affect cognitive functions, such as learning and spatial memory. Accordingly, the recovery of allopregnanolone concentration induced by progesterone administration results in a significant increase in sexual motivation, while the subsequent blocking of its synthesis by finasteride decreases proceptive behaviors. These results suggest that the reduction in allopregnanolone concentrations induced by OCs treatment might be relevant to the side effect sometimes exhibited by women taking these drugs.