Complex risk factors underlie a complex disease

Risk factors for having migraine itself, and risk factors for progression from episodic to chronic forms of the disorder overlap but are not the same, said Stephanie Nahas (Thomas Jefferson University, Philadelphia, Pennsylvania, USA) when interviewed by patient advocate Amy Mowbray during the 2023 Migraine World Summit.¹

Can chronicity be avoided?

Migraine is a chronic disease. But chronic migraine as a diagnosis is defined as having 15 or more headache-affected days per month (of which at least eight are treated as migraine) for at least three months, Dr Nahas told the audience.

Over-reliance on acute medication risks progression to chronicity

In risk of progression to chronic migraine, a higher number of headache days at baseline is a factor: risk starts to increase in people with more than one episode per week.

So too is over-reliance on acute medication for treatment. This is especially the case with triptans (if they are used for more than around ten days per month), and with opioids. That said, Dr Nahas emphasized that there is great variability between individuals in their susceptibility to migraine chronification through very frequent use of acute medication.  

Risk factors for developing migraine and, more specifically, episodic migraine include comorbid anxiety or depression, but also physical health factors such as asthma and obesity. Poorly controlled insomnia, perhaps due to sleep apnea, increases migraine risk – as may hypermobility affecting the neck.

Among preventable risk factors, Dr Nahas identified adverse effects due to lack of early treatment of migraine. Though the condition frequently begins in childhood, the fact that complaints made by children may not be believed – along with stigma associated with the migraine diagnosis – mean that opportunities for early effective intervention are often missed.

But gender and age stand out as the clearest risk factors. Peak migraine prevalence is among women aged around 25 to 45 years, when there is a 3:1 ratio of female to male cases.

Patience needed when waiting for postmenopausal improvement

Hormones – stability or chaos?

Natural hormonal fluctuations can trigger migraine during the regular menstrual cycle. But their role as a risk factor in migraine is especially evident during the perimenopause when estrogen levels fluctuate wildly and progesterone is produced only during infrequent and irregular ovulation. “Hormone chaos” is not an unreasonable description, Dr Ann MacGregor (St Bartholomew’s Hospital, London, UK) said during her interview with Elizabeth DeStefano.²

Independently of the sex hormones, heavy and painful menstrual bleeding during the perimenopause is associated with increased release of prostaglandin, which can also act as a migraine trigger.

Turning back to the sex hormones, we might expect that the new relatively stable, low estrogen state established post-menopausally would reduce risk of a migraine. And that is often the case. But Dr MacGregor had two points of caution. First, the shutting down of ovarian estrogen production (as opposed to the cessation of ovulation) is gradual – taking perhaps five years – so patience may be needed before improvement in headache burden is seen.

Secondly, while a reduction is generally seen in migraine without aura, migraine with aura – which has a different etiology -- may not improve postmenopausally and indeed may appear then for the first time.

Stress stands out as risk factor in patient-derived data

Migraine Buddy is the largest app used by people with the condition, and has 3.3 million registered users, with Japanese second only to English as the most common language on the platform, Francois Cadiou, who founded the app, told Carl Cincinnato.³

Its large and worldwide reach generates enormous amounts of data, but extracting meaningful patterns from that information is a daunting task. This is evident, for example, in efforts to understand whether the weather – notably a fall in barometric pressure – is a risk factor.

The answer may be that it is related to migraine incidence for some people at some seasons in some parts of the world, but any potential effects of pressure are difficult to disentangle from temperature, and humidity and UV light, Francois Cadiou said. And any effect of triggers, alone or in combination, is likely to be very individualized.

In relation to foods, there is a similar lack of consistent, predictable effect: potential triggers are very difficult to distinguish from what may be abnormal eating preferences caused by prodromal brain dysfunction.

But Francois Cadiou is reasonably confident that data derived from Migraine Buddy support the role of work-related stress as a risk factor. This is evident in the annual fall in migraine episodes around three days after 20^th December, when people start the midwinter holiday period. And a reduction in migraine episodes was also seen in the COVID-19 pandemic when people started working from home.