Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study

Background: Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked
CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe,
treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone
serum levels between women with menstrually-related migraine (MM, n¼30) or postmenopausal migraine
without aura who had suffered from menstrually-related migraine during their fertile age (PM, n¼30) and non-headache
control women in fertile age (FAC, n¼30) or post-menopause (PC, n¼30).
Methods: Participants were women with migraine afferent to a headache centre; controls were female patients’
acquaintances. Serum samples obtained were analyzed by HPLC-ESI-MS/MS.
Results: In menstrually-related migraine and postmenopausal migraine groups, allopregnanolone levels were lower than
in the respective control groups (fertile age and post-menopause) (p<0.001, one-way analysis of variance followed by
Tukey-Kramer post-hoc comparison test) while progesterone and testosterone levels were similar. By grouping together
patients with migraine, allopregnanolone levels were inversely correlated with the number of years and days of migraine/
3 months (p 0.005, linear regression analysis).
Conclusion: Decreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to
menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a
rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.