Progesterone, Migraines, And The Sex-Differentiated Effects Of Hormones

After puberty, migraines become 3 times more likely for women compared to men (Kelley, 2023). This large difference in migraine occurrence can be attributed to many factors, but it appears that sex hormones play a large part in this differentiation. According to an article titled“ Why Do Women Suffer Migraines More Frequently And Severely Than Men,” neurologists explain that rapid fluctuations in hormones like estrogen and progesterone can be responsible for these migraine attacks. Women experience large changes in hormones during menstruation, pregnancy, menopause, perimenopause, and puberty, where they experience rapid fluctuations in estrogen and progesterone. Recent neuroscience findings suggest that progesterone can have neuroprotective properties due to its interaction with the brain-derived neurotrophic factor (BDNF). The connection between the neuroprotective effects of progesterone and natural fluctuations in sex steroid hormones in women that lead to migraines can help elucidate possible treatments for migraines in women in particular. 

The article titled, “Brain-derived neurotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotective” by Singh et al. explores the mechanisms behind progesterone and its interaction with BDNF. In particular, researchers found that the natural progesterone interacts with the expression of PRs or progesterone receptors. These receptors, specifically pgrmc1, are bound to lead to the release of brain-derived neurotrophic factors. This factor is implicated in neuronal cervical pathways, ultimately leading to less brain cell damage and protection against traumatic brain injury and other neurodegenerative diseases (Singh et al. 2024). The researchers emphasized that progestrogens' role in the body is beyond just its role in reproduction. It has significant effects on the brain and neurological health, and in particular neuroprotective benefits. According to the researchers, progesterone can, “… potentially direct future advancement and capability of developing more effective treatments for symptoms of the menopause, and those (neurodegenerative) diseases whose risk or incidence increases during the post-menopausal period.” (Singh, et al., 2024). Therefore, there is a clear connection between progesterone's neuroprotective properties and its possible role in mediating the negative symptoms of periods of hormonal imbalances like menopause and pre-menopause. 

In the news article titled, “Why Do Women Suffer Migraines More Frequently and Severely Than Men?” neurologist Laura Kelley explains that migraines occur almost 3 times more frequently in women compared to men. Furthermore, she explains that migraines are more severe in women compared to men. Women are more likely to experience nausea, vomiting, and sensitivity to light and sound compared to men. Women are also more likely to seek emergency care as a result of severe migraines (Kelley, 2024). She highlights that 50 to 60% of women experience migraines as a result of menstruation, as a result of rapid changes in estrogen during ovulation. This is in part due to the drop in estrogen at this time. She also notes that although migraine frequency increases in the first trimester of pregnancy, many women experience improvement in the later stages as a result of gradual increases in hormonal levels. If hormonal changes have such a dramatic effect on the quality of life of women experiencing migraines, the implications of possible neuroprotective effects of progesterone can be a further research pathway in treating these symptoms. 

If Progesterone and in connection to it BDNF levels are important for neuroprotective and brain inflammation, exploring its possible effects on migraines in women could lead to new treatments for severe migraine frequency during pregnancy and menstruation. Possibly, without the interference of other pharmaceuticals and treatments, progesterone therapy alone can help women who suffer from migraines. Additionally, further research into this connection can help elucidate more roles progesterone plays in brain diseases and neurological conditions like migraines. 

References

1. Kelley, L. (2023, June 21). Why Do Women Suffer Migraines More Frequently and Severely Than Men? University Of Colorado. https://news.cuanschutz.edu/news-stories/why-do-women-suffer-migraines-more-frequently-and-severely-than-men

2. Singh, M., Krishnamoorthy, V. R., Kim, S., Khurana, S., & LaPorte, H. M. (2024). Brain-derived neuerotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotection. Frontiers in Endocrinology, 15, 1286066.