Sex hormones’ role in neurological illnesses deserves greater scrutiny, JGH neurologist advises

Migraine, epilepsy, sleep disorders and more can be influenced by sex hormones, says Dr. Hyman Schipper

A veteran JGH neurologist and researcher has issued a firm reminder to physicians to be mindful of the crucial and frequently overlooked role that sex hormones play in numerous neurological diseases and related medical conditions, particularly in women.

According to Dr. Hyman Schipper, who is a staff neurologist at the JGH and Senior Investigator at the Lady Davis Institute, treatments for a broad range of illnesses—including migraine, strokes, epilepsy, sleep disorders, Alzheimer’s disease and even some types of brain tumours—have a better chance for success when the impact of sex hormones on the patient’s brain is taken into account.

Dr. Schipper, who is also Professor of Neurology at McGill University, cites the example of a woman who is using the birth control pill and then develops epilepsy. In all likelihood, a neurologist would not think to ask about her use of the pill and would prescribe conventional anti-epileptic medications to control the seizures.

“However, many commonly used anti-seizure drugs will cause the patient’s liver to consume the hormones that are in the birth control pill, and this will cause the pill to fail,” he explains. “This is an important fact worth knowing, because we can prescribe anti‑epileptic medications that don’t interact with sex hormones.”

Dr. Schipper says new insights are also enabling some earlier conclusions to be refined—notably, about the use of estrogen in treating Alzheimer’s disease. Around 2003, research revealed that using estrogen for that purpose was bad for patients, which led doctors to stop administering hormone replacement therapy in those cases.

However, more recently, researchers and epidemiologists have shown that a window of opportunity exists: If estrogen is administered within the first few years of menopause, the outcome in treating Alzheimer’s will probably be positive. However, the patient is likely to worsen if hormone replacement therapy is started more than 10 years after menopause.

An emphasis on women’s neurological illnesses

Dr. Schipper notes that he is referring primarily to female patients, because their hormones (particularly estrogen and progesterone) have a greater effect on illnesses in women than male sex hormones (especially androgen) have on illnesses in men.

This is because hormonal fluctuations in women—when they menstruate or as they enter menopause—can often be correlated to day-to-day variations in illnesses such as epilepsy or migraine, he explains.

Meanwhile, he adds, “we really don’t have as good a handle on the role of androgens on male neurologic disease, because androgens don’t undergo cyclical changes, which means a connection to men’s illnesses is harder to establish.”

His detailed observations appear in the journal Brain Medicine in an article he wrote to celebrate the 100^th birthday of one of his mentors, Dr. Seymour Reichlin.

Dr. Schipper, who joined JGH staff in 1988, is in the uncommon position of having expertise in both neurology and endocrinology, having earned a Ph.D. for studying the negative effects of estrogen on certain parts of the brain.

As a result, he says, “I can now use the tools of an endocrinologist to treat neurological symptoms when they’re linked to hormones.”

His article is intended to bring his colleagues in neurology up to date on the latest developments in the two overlapping fields, while impressing upon neurologists the importance of considering the effects of sex hormones when treating illnesses of the brain.

“My article pulls together findings from a lot of the medical literature that many neurologists might be unaware of,” Dr. Schipper says. “This can be of great benefit to them and their patients, since neurologists may be unfamiliar with recent developments in reproductive medicine.”

Investigating the potential of neurosteroids

For Dr. Schipper, one of the most interesting fields of current inquiry is neurosteroids, which are compounds of estrogens and progestins that are made in the brain and are active there. Progesterone, for instance, is produced in the ovaries, but once it enters the brain, it is converted into another compound that affects the nervous system differently from progesterone.

The possible benefits of all sorts of neurosteroids are now being explored, Dr. Schipper says. For example, a compound called ganaxolone (a neurosteroid derived from progesterone) has “impressive anti-epileptic effects, but without the feminizing effects of the female hormone.” As a result, it holds promise for the treatment of drug-resistant epilepsy, especially in children.

The relationship between Alzheimer’s disease and estrogen has been studied for 30 years, Dr. Schipper says, but only in recent years have neuroscientists been looking more closely at the connection between Alzheimer’s and neurosteroids.

“There’s also been growing interest in the correlation between neurosteroids and other movement disorders, such as Parkinson’s disease,” he adds. “That’s why so much effort is being made in trying to manipulate not only the original hormones, but the neurosteroids that are derived from those compounds.

“This tells us that further research is vital, especially where neurosteroids are concerned. We’ve known about them for a relatively short time, but they have the potential to open up a whole new ball game in terms of understanding how hormones can affect neural function in health and disease.”