Dehydroepiandrosterone Sulfate, Dehydroepiandrosterone, 5α-Dihydroprogesterone and Pregnenolone: Serum Analysis and Correlation Between Migraine and Non-headache Control Females

Migraine is a very painful and disabling disorder of the nervous system (NS) affecting about 10% of the world's adult population, especially women and it is associated with a variety of comorbidities [1, 2]. Neuroactive steroids have pleiotropic actions on the NS. Alterations in their peripheral and central levels could be involved in the pathogenesis, still not fully understood, of migraine and its comorbidities [3]. The purpose of our exploratory study (approved by Modena Ethical Committee) was to determine serum levels of dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), 5α-dihydroprogesterone (DHP) and pregnenolone (PREGNE) in women suffering from migraine without aura (n=30) and age-matched non-headache control females (n=30). The patients were enrolled at the Headache Centre of Modena; controls were patients’ contacts. Calibrators and serum samples were spiked with the ISs solution and treated to deplete proteins and phospholipids. The obtained extracts were evaporated to dryness, derivatized and analysed by RP-LC-ESI-MS/MS in MRM mode. Analyte’s levels were determined by interpolation on the regression curves, generated from the analyte quantifier ion peak area to the corresponding IS. Migraine women presented significantly lower levels of DHEAS, DHEA and DHP compared to controls (P<0.05) and the found concentrations negatively correlated with migraine history, and migraine days in the last three months (P< 0.05). These results parallel to our previous studies showing reduced serum levels of allopregnanolone and pregnenolone sulfate in migraine women [4,5]. The low serum levels found for both inhibitory and excitatory neurosteroids indicate that migraine women may suffer from inadequate neuroprotection, anti-inflammation activity and pain modulation. These deficits could represent the link between migraine and its various comorbidities. References [1] Headache classification Committee of the International Headache Society (IHS). Cephalalgia 2018, 38,1–211. [2] Yin JH., Lin YK., Yang CP., et al. Headache 2021. doi: 10.1111/head.14106. Online ahead of print. [3] Yilmaz, C.; Karali, K.; Fodelianaki, G.; et al. Front Neuroendocrinol 2019, 55, 100788. [4] Rustichelli, C.; Bellei, E.; Bergamini, S.; et al. Cephalalgia 2020, 40, 1355-1362. [5] Rustichelli, C.; Bellei, E.; Bergamini, S.; et al. J Head Pain 2021, 22, 13.