Progesterone's Protective Effects: Neuroprotection and Migraine Relief

Progesterone is a hormone known for its reproductive functions, such as its role in female fertility, embryo implantation, maintenance of the uterus and ability to assist in preventing miscarriage and preterm labor. However, as more research into this progestin has been conducted, more benefits have been discovered including its protective effects.

In the research paper, “Brain-derived neuerotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotection,” Dr. Meharvan Singh and his colleagues analyze these protective effects of progesterone. The Singh Laboratory found that progesterone increases the expression and release of neurotrophins, such as BDNF (brain-derived neurotrophic factor), which are at least partially responsible for progesterone’s protective effects. BDNF has been shown to play a critical role in synaptic plasticity, cognitive function, and cell viability; one of the many examples of BDNF’s therapeutic processes is its demonstrated ability to repair tissues in various stroke animal models. Researchers showed that treatment with progesterone led to a BDNF expression in an animal model of TBI. Increased levels of progesterone and BDNF assist with cognition and plasticity and can assist with the protection against stroke, traumatic brain injury, and neurodegenerative diseases, such as Alzheimer’s disease.

Progesterone’s protective effects may extend beyond stroke, TBIs, and neurodegenerative diseases into neurovascular disorders, such as migraines. Migraines, intense headaches often coupled with a variety of other symptoms ranging from nausea to visual disturbances, are often impacted by hormonal fluctuations. The research paper, “Considerations for hormonal therapy in migraine patients: a critical review of current practice” by Romy van Lohuizen et al. analyze the effects of hormones, including progesterone, on migraine, especially within women. About two-thirds of women experience menstrual-related migraine, and while estrogen withdrawal is considered a migraine trigger, progesterone is believed to have protective effects. According to Lohuizen and their colleagues, progesterone demonstrates these effects by “modulating nociception and downregulating estrogen receptors.”  Progesterone can modulate nociception by reducing activation in the trigeminal nucleus caudalis. Additionally, the active metabolite of progesterone, allopregnanolone, has been shown to positively modulate GABA receptors in animal studies which have shown antinociceptive effects.

Although Dr. Singh et al. primarily analyze aging and neurodegenerative diseases, and Dr. van Lohuizen et al. primarily analyze female identifying migraine patients, both research articles demonstrate the protective effects of progesterone.

 

References:

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. https://doi.org/10.3389/fendo.2024.1286066

van Lohuizen, R., Paungarttner, J., Lampl, C., MaassenVanDenBrink, A., & Al-Hassany, L. (2023). Considerations for hormonal therapy in migraine patients: a critical review of current practice. Expert review of neurotherapeutics, 24(1), 1–21. Advance online publication. https://doi.org/10.1080/14737175.2023.2296610