Hormone replacement therapy and headache prevalence in postmenopausal women. The Head-HUNT study

Conflicting evidence exists whether hormone replacement therapy (HRT) is a risk factor for headache. The aim of the study was to examine the prevalence of headache and migraine amongst postmenopausal women using HRT. In the Nord-Trøndelag Health Study 1995–97 (HUNT 2), 18 323 (62%) out of 29 679 women aged 40 years or more responded to headache questions (Head-HUNT). Amongst the 6007 postmenopausal women, 5507 (92%) responded to questions regarding use of HRT (2375 used or had used it) and questions related to headache (2407 had complaints). There was a significant association between headache and present use of HRT, both with local [odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.1–1.7] and systemic (OR = 1.6, 95% CI 1.4–1.9) application. This was found for non-migrainous headache (OR = 1.3, 95% CI 1.1–1.5) and migraine (OR = 1.6, 95% CI 1.4–1.9). Both migraine and non-migrainous headache were more probably amongst users of postmenopausal HRT than amongst those who had never used HRT. Whether HRT caused headache or was used partly because of headache cannot be determined in this cross-sectional study.     

Reference programme: Diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 2nd Edition, 2012

Genetic factors importantly contribute to migraine. However, unlike for rare monogenic forms of migraine, approaches to identify genes for common forms of migraine have been of limited success. Candidate gene association studies were often negative and positive results were often not replicated or replication failed. Further, the significance of positive results from linkage studies remains unclear owing to the inability to pinpoint the genes under the peaks that may be involved in migraine. Problems hampering these studies include limited sample sizes, methods of migraine ascertainment, and the heterogeneous clinical phenotype. Three genome-wide association studies are available now and have successfully identified four new genetic variants associated with migraine. One new variant (rs1835740) modulates glutamate homeostasis, thus integrates well with current concepts of neurotransmitter disturbances. This variant may be more specific for severe forms of migraine such as migraine with aura than migraine without aura. Another variant (rs11172113) implicates the lipoprotein receptor LRP1, which may interact with neuronal glutamate receptors, thus also providing a link to the glutamate pathway. In contrast, rs10166942 is in close proximity to TRPM8, which codes for a cold and pain sensor. For the first time this links a gene explicitly implicated in pain related pathways to migraine. The potential function of the fourth variant rs2651899 (PRDM16) in migraine is unclear. All these variants only confer a small to moderate change in risk for migraine, which concurs with migraine being a heterogeneous disorder. Ongoing large international collaborations will likely identify additional gene variants for migraine.