Examining the Role of Sex Hormones in Migraine

Chronic pain, including migraine pain, represents a social and economic burden for those who suffer from it. A recent review evaluated current data on the effects of sex hormones on transient receptor potential (TRP) channels, which contribute to the sensitization in migraine and chronic pain syndromes. The data suggested that the modulation of TRP channels’ expression and activity by gonadal hormones provide novel pathways for drug intervention.

“This gender prevalence in migraine appears to be related to sex differences arising from both gonadal and genetic factors. Indeed, the functionality of the somatosensory, immune, and endothelial systems seems modulated by sex hormones, as well as by X-linked genes differentially expressed during development,” the authors stated. “Here, we review the current data on the modulation of the somatosensory system functionality by gonadal hormones.”

The review suggests that there is evidence demonstrating a direct regulation of nociceptor activity by sex hormones at transcriptional, translational, and functional levels. The research specifically focuses on the direct interaction and modulation of thermoTRP channels by sex hormones, which may represent targets for migraine intervention.

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The authors noted that migraine prevalence changes across all age ranges. For women, the prevalence was often higher, except for a sharp decrease at menopause. Although several previous studies found that low levels of estrogen are related to an increase in migraine attacks, others suggest that estrogen promotes migraine episodes.

The authors discussed the presence of TRPV1 channels in the brain regions that are influenced by sex hormones and how there is clinical evidence relating the function of estrogens with TPV1 activity.

“There is no doubt about the existence of a sex difference prevalence in chronic pain conditions such as migraine, where the prevalence in women is 2 or 3 times greater than in men,” the authors wrote. “Although the specific molecular and cellular mechanisms underlying this sex dimorphism are still under intense investigation, a pivotal role of sex hormones regulating the somatosensory system appears clear.”

Although it has previously been hypothesized that sex hormones mainly act to regulate the immune system, the authors explained that recent evidence reveals sex hormones’ direct role in modulating nociceptor signaling. Furthermore, sex hormones can regulate the expression thermoTRP channels and signal pathways that sensitize their activity. The authors suggest that understanding the role of sex hormones on chronic pain will lead to the development of more efficient therapies.

“Nonetheless, it should be taken into consideration that sex hormones may not be the only players in determining sexual dimorphism in migraine pain, as this is a very complex phenomenon involving both gonadal-dependent and independent mechanisms that most likely complement each other in defining sex differences in migraine and chronic pain disorders,” concluded the review.