MENSTRUAL MIGRAINE: PREVALENCE AND SEVERITY

Menstrual Migraine (MM) is a disabling, aggressive form of migraine that affects approx. 50 million women worldwide.

The International Classification of Headache Disorders defines MM as migraine attacks that start up to two days before the period begins, then continue three or more days into the menstrual flow. The primary characteristics of MM attacks are how predictable, prolonged and disabling they are—making Menstrual Migraine a major public health problem.

  • THE WHO RECOGNIZES MIGRAINE AS THE LEADING CAUSE OF LIFE LIVED WITH A DISABILITY FOR WOMEN OF A REPRODUCTIVE AGE
  • 1-in-10 people worldwide suffer from migraine – making it more prevalent than diabetes and asthma combined.
  • 2/3 of these, approx. 500 million, are women, half being of a fertile age
  • 1-in-5 of these women, or approx. 50 million women worldwide, suffer from Menstrual Migraine
“For five days every month normal life grinds to a halt, and disabling pain takes over. I kid myself I’m managing it—but in reality, it’s controlling me.”

Therese’, 38, Germany.

PREVENTION IS THE BEST CURE:

MM is a severe, highly specific form of migraine with a unique symptomatology but no specific treatment. Until now.

In 2019 Asarina Pharma will begin a clinical Phase IIA trial for Sepranolone, the world’s first therapy to specifically target MM. As a prophylactic treatment Sepranolone has been designed to prevent Menstrual Migraine symptoms from occurring, not just treat them. How will Sepranolone do it?

PHASE IIA TRIAL: KEY FACTS

TARGET SITES: Finland, Denmark, Sweden
NUMBER OF PATIENTS: 78-90
AGE OF PATIENTS: 18 – 45 yrs
CRO: SCRO (Scandinavian CRO) based in Uppsala Sweden
TREATMENT: prophylactic neurosteroid Sepranolone
ADMINISTRATION: pre-filled syringes for self-administration
TIMELINE: study start in late June 2019 – completed end 2020

“Menstrual Migraine can be the most challenging kind to treat, and frequently does not respond to the same medicines that work the rest of the month.” The American Migraine Foundation

MM ATTACKS ARE OFTEN RESISTANT TO STANDARD TREATMENTS

Why is it so important that Sepranolone is preventive? MM attacks are often resistant to standard, symptomatic treatments. For example: A woman with two or three migraine attacks a month on top of her menstrual migraine attacks, will typically find that whilst her standard preventive treatment may work successfully for her non-menstrual attacks—it won’t have any effect on her MM attacks.

With often longer bouts of pain the temptation with MM can be to take symptomatic therapies in large amounts over long periods, causing concern over how much treatment to take, how long it can be taken for, relapse of symptoms over several consecutive days and associated menstrual disorder. As a prophylactic cure, Sepranolone avoids these concerns.

New prophylactic therapies represent a new paradigm shift in migraine treatments. Sepranolone is unique amongst them. None of the clinical studies for recently launched new antibodies against migraine, for example, have specifically analyzed their effect in women suffering from menstrual migraine. Sepranolone offers powerful benefits to women managing menstrual migraine over a lifetime.

MIGRAINE – OR MENSTRUAL MIGRAINE?

MENSTRUAL MIGRAINE is a unique disease requiring a unique treatment. Attacks are more predictable, but often more severe, prolonged and disabling too. And they commonly fail to respond to conventional treatments.
So what are the signs, and how can doctors and patients tell which kind of Migraine they are dealing with?

MENSTRUAL MIGRAINE

MM is predictable. Sufferers know when it will come.

MM sufferers are more likely to ‘suffer in silence’. Because it is predictable MM sufferers often choose to ‘manage’ the condition themselves and are poorly represented in clinics.

MM is frequently undiagnosed. Few non-specialist clinicians ask when migraine attacks occur in relation to the period.

MM receives little clinical research. Fewer diagnoses means little presence in clinical trials. The number of clinical papers on Menstrual Migraine compared to migraine is low.

MM has no dedicated prophylactic therapy

EPISODIC MIGRAINE

Migraine is unpredictable, often referred to as a ‘fickle’ disease’

Migraine sufferers are more likely to actively seek help. Migraine sufferers not only seek diagnosis and help from GPs but also appear regularly in pain clinics seeking help from neurologists.

Migraine is usually well diagnosed. Clinicians ask about the frequency and severity of attacks, diagnosing migraine more reliably.

Migraine is well researched, in fact a booming research area. As well as a wide range of existing treatments, the pipeline for novel Migraine therapies is extensive too.

Migraine has a wide range of treatment options including both symptomatic and prophylactic

MEET THE MENSTRUAL MIGRAINE EXPERTS

Asarina Pharma’s Phase II Menstrual Migraine study is being led by Chief Medical Officer Märta Segerdahl and Scientific Advisory Board member and world authority on menstrual migraine Professor Anne MacGregor.

“The WHO recognizes migraine as being the leading cause of life lived with a disability for women in their reproductive years. Menstrual Migraine clearly needs to be targeted and treated as a specific disease entity.”,

Prof Anne MacGregor. Award-winning migraine researcher, educator and clinician with 5 books and over 200 research papers to her name.
AnneAndMarta

In February 2019 PROFESSOR ANNE MACGREGOR and Asarina Pharma Chief Medical Officer DR MÄRTA SEGERDAHL met in Copenhagen to discuss MM. An aggressive form of migraine characterised by prolonged, predictable and disabling attacks, it affects 50 million women worldwide, yet has never had a dedicated therapy… until now.

Why is a specific treatment for Menstrual Migraine so important?

PROF MACGREGOR: MM attacks are often resistant to standard treatments. In my practise I meet many women who are already under neurologists for management of their episodic migraine, but they end up coming to me, saying “I’m on a lot of drugs for migraine, they work really well for my regular attacks—but I’m still left with other attacks that happen every month with my periods, and my neurologist doesn’t know what to do about it. The dose of the standard treatment just gets upped, which then increases the side effects.”
Because Menstrual migraine attacks can be longer than episodic attacks, patients get concerned over how much standard treatment it is safe to take, how long it can be taken for, and relapse of symptoms over several consecutive days. So standard treatments do not properly manage migraine attacks with menstruation.

How well recognized and diagnosed is Menstrual Migraine?

PROF MACGREGOR: The big challenge right now is recognition. The medical profession is not well educated yet in how to manage menstrual migraine. MM patients often know more about managing their condition than many of their treating doctors do. Currently 50% of people with migraine self-help without even seeking proper treatment. But as soon as an effective treatment starts to become available for a condition, then it starts to be better recognized, which in turn makes the treatment more available and accessible to those living with it.
We want neurologists to recognize MM as an entity in itself. We need to help them feel comfortable dealing with something that is not directly neurological but which falls in their treatment field, and encourage them to combine the insights of neurology and gynaecology.

DR SEGERDAHL: It’s important for neurologists to know that Sepranolone is not a steroid hormone. Because in order to be a steroid hormone, apart from being a steroid, it also needs to have hormonal activity. Sepranolone is a hormone metabolite and an endogenous compound. Early adopters of new treatments are always specialists rather than GPs, and that’s how it will be with MM. We need to spread the word top-down. Uptake will be driven too by the scale of the prevalence and the need. There are still more women with migraine then there are with diabetes or asthma combined.

PROF MACGREGOR: MM is a disease entity, it affects a specific group of women and there are dedicated treatments for it—understanding this will generate better diagnoses.

Could you describe the impact of Menstrual Migraine on a typical family?

PROF MACGREGOR: Many of the people I see have had to completely alter their working lives as a direct consequence of their migraine. Many are unable to hold down a full-time job at all. Or they’ll chose shift work or working from home, just to avoid having to be at a certain place at a certain time on specific days. Women with MM often have to have a network of friends or relatives they can call on to help them go and pick up the children or other basics. So it is not just the individual sufferers themselves who experience migraine—but everyone around them.

Professor Anne McGregor

Prof Anne MacGregor has published five books and over 200 research papers on menstrual migraine and headache. A world authority, she began training in headache medicine and studying the vital links between the menstrual cycle and migraine at St Bartholomew’s Hospital London.In 2002 she received the Elizabeth Garret Anderson Award for women who have made an extraordinary contribution to long-term work in headache relief. In 2011 she received the Special Recognition Award and Honorary Life Membership from the International Headache Society.

Why do so many women with MM ‘suffer in silence’?

PROF MACGREGOR: There’s still a stigma around migraine. A sense that it’s the individual sufferer’s “fault”. They “can’t cope”, they’re not “pulling their weight.” Rather than understanding it as an identifiable disease entity with a purely chemical basis. Which it is—because when the attacks happen there’s nothing you can do about that chemical change. You’re not in control of it.

Yet the media still produce articles telling us ‘Migraine is triggered by chocolate’, or ‘you’ll get an attack if you don’t take regular vitamin supplements’, implying that sufferers are doing things wrong. People with MM often end up leading really restricted lives in an effort to curtail symptoms—with absolutely no effect.

And because people see them after their attacks, when they’ve recovered and look fine, they often just don’t believe that person has been lying down in a darkened room totally unable to move. Some MM sufferers phone their doctors and ask them to visit during their attack, just so they will be believed. So diagnosis can be a powerful affirmation for sufferers who are often made to feel they’re imagining it. It tells them they are being believed and helps them understand what is actually going on.

How important is the science of Sepranolone, allopregnanolone and hormone metabolites?

PROF MACGREGOR: it’s really exciting to look at MM in a different way. To consider other pain pathways, how steroid hormones work together and how the same ultimate problem develops from different routes—which is exactly how migraine works. There has been growing awareness of Migraine over recent years, but it hasn’t always translated into action and innovation in research. Right now nobody is looking at mechanisms. And yet knowing more about the mechanisms of MM is crucial. Not only will it provide an effective management strategy, it will help us better understand the whole pathophysiology of migraine.

Asoc Prof Märta Segerdahl

Asoc Prof Märta Segerdahl has over 25 years’ clinical and strategic experience in anaesthesiology and pain medicine, including menstrual migraine. She gained her Medical License and Doctorate from Karolinska Institutet, and was a senior consultant at pain clinics in Karolinska and Huddinge Hospitals in Stockholm, heading the latter. She is currently an Associate Professor at Karolinska Institutet, Stockholm, and Chief Medical Specialist for Clinical Development Neurology for Danish pharma company Lundbeck.

DR SEGERDAHL: People have been so focussed on vasodilation for so long with migraine, because it’s something you can see and measure. Because you can measure hormones there’s been a lot of research into hormone fluctuations, but not into how we metabolize hormones. And that is super-important.


PROF MACGREGOR: The beauty of this Study is that it puts the management of MM back into the hands of the women who have the problem, with the diagnosis confirmed by somebody who knows what MM is. Given that humanity has yet to find a cure or really understand what causes migraine, a condition that’s been around since Babylonian times, it’s unlikely we’ll find a single cure for Menstrual Migraine—but to have a realistic opportunity to provide women with a treatment that gives them back control over their condition—so they are in control of their lives, not having migraine attacks controlling their lives, I think that would be really hopeful.

MIGRAINE AND MENSTRUAL MIGRAINE FOUNDATIONS AND SUPPORT GROUPS

Few information or user resources focus specifically on Menstrual Migraine. However, many excellent Migraine resources with valuable sections on MM.