Role of Allopregnanolone in Menstrually Related and Postmenopausal Migraine

Serum allopregnanolone levels are lower in women with either menstrually related or postmenopausal migraine compared with women without headache, suggesting a potential role for allopregnanolone analogs for the management of these women, according to study results published in Cephalalgia.

Previous studies have shown an association between low levels of allopregnanolone in the peripheral blood or cerebrospinal fluid and premenstrual dysphoric disorder, premenstrual syndrome, and catamenial epilepsy. Hormonal fluctuations are also suspected to have an important role in menstrual migraine.

The goal of the current study was to explore the role of allopregnanolone in menstrually related and postmenopausal migraine. Furthermore, the researchers assessed serum levels of progesterone and testosterone in women with migraine.

The cross-sectional study included 30 women aged 18 to 45 years (mean age, 33.5 years) with menstrually related migraine without aura and 30 (mean age, 30.9 years) age-matched control women without migraines. In addition, the cohort included 30 women (mean age, 56.6 years) with postmenopausal migraine and 30 (mean age, 56.1 years) age-matched control women without migraines.

In the group of women with menstrual migraine, levels of allopregnanolone were significantly lower than in the control group (mean, 52 vs 78 pg/mL; P <.001), while progesterone and testosterone levels were not significantly different between the groups.

In a similar fashion, levels of allopregnanolone were significantly lower in women with postmenopausal migraine compared with the respective control group (mean, 25 vs 80 pg/mL; P <.001). Progesterone and testosterone levels were not significantly different between the groups.

When grouping together women with menstrually related and postmenopausal migraine, an analysis revealed a negative correlation between serum levels of allopregnanolone and years of migraine (P =.001) and number of migraine days in the preceding 3 months (P =.005).

The study had several limitations, according to the researchers, including the small sample size, being a pilot study, and measurement of allopregnanolone levels in different menstrual cycles.

“Our findings, obtained in a pilot study, if confirmed in larger case series, could provide the background for novel therapies aimed at raising the GABAergic transmission by drugs increasing the biosynthetic pathway of inhibitory neurosteroids or by the use of synthetic allopregnanolone analogues for the treatment of both menstrually-related and postmenopausal migraine,” concluded the researchers.

Reference

Rustichelli C, Bellei E, Bergamini S, et al. Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: a cross-sectional study [published online June 26, 2020]. Cephalalgia. doi:10.1177/0333102420937742