Neurological – and other diseases, for that matter – often present differently or require a different approach in women and men because their genetics, biology and life cycles differ. Doctors treating a pregnant woman, for example, have two patients: the mother and her developing fetus.
Yet, for much of history, neurological diseases in women were regarded as no different than those in men, said Mary Angela O’Neal, MD, Chief of General Neurology at Brigham and Women’s Hospital in Boston and director of the Women’s Neurology Program.
“When I began doing this work in 2010, there was one other women’s neurology program in the country. That’s changed,” she said. “It’s becoming much more mainstream.”
Part of the uptick in women’s health research is the growing recognition of the need for data of sex as a biological variable in health and disease. Not until 1993 were women included in clinical trials and only in 2014 did the National Institutes of Health (NIH) require inclusion of both male and female animals in most funded preclinical research.
For many years, research has focused on so-called “women’s issues” — fertility, menstruation and menopause. However, the increasing availability of clinical research and outcomes data are expanding women’s health innovation. When Cure asked healthcare industry leaders for their top therapeutic interest in women’s health, traditionally “women’s health” therapeutic areas didn’t even crack the top five. Instead, respondents listed neurology as the therapeutic area of most interest. Cure reported this and other findings in Unlocking the Opportunity: What’s Needed to Innovate, Invest and Influence Women’s Health. Women’s Health Benchmark Report 2024.
For O’Neal, her focus on neurological disorders spans all stages of women’s lives: through menstruation, pregnancy, menopause and aging. She studies how sex differences influence the development and expression of neurologic disorders and how psychosocial sex differences – including the relatively recent phenomenon of trans women taking high doses of female hormones – influence neurologic disease.
Sex as a biological variable in neurological diseases
Sex differences are pronounced in many neurological diseases, including:
Multiple sclerosis is more common in women than men and may occur at a younger age. Women are more likely to have inflammatory lesions and frequent relapses. Higher levels of sex hormones can have an anti-inflammatory effect, but they fluctuate and can produce significant changes in symptoms as a woman progresses through pregnancy and menopause.
Stroke: Women over the age of 75 are more likely to have severe strokes with worse outcomes. Complications of pregnancy can predispose women to strokes later in life.
Alzheimer’s disease: Women make up nearly two thirds of those who have the ailment. Partly because they live longer, women are more likely than men to develop dementia in their lifetimes. It also appears that women process the amyloid protein differently than men.
Migraine: Migraines are diagnosed more often in women than in men; women tend to experience more frequent, longer, and more disabling attacks.
Women, whether born with two X chromosomes or transgender, are fundamentally different than men. A key difference for both groups is the powerful influence of female hormones, which govern maturation, fertility, pregnancy, lactation and menopause. Hormonal ebbs and flows affect everything relating to a women’s health, including the onset, presentation and course of neurological illness.
Doctors are still trying to understand how these differences affect the course of neurological diseases, and the paradoxes that may sometimes result.
For example, although women are more prone to multiple sclerosis than men, pregnancy protects against relapsing and remitting disease, said Mysti Harrison, MD, MSCR, Assistant Professor of Neurology, Adult Neurology, Multiple Sclerosis & Neuroimmunology at Washington University School of Medicine in St. Louis and Barnes Jewish Hospital.
“That means women are less likely to suffer exacerbations of the illness during pregnancy, probably due to pregnancy related hormones,” Harrison said.
O’Neal said treating neurological ailments in women can be challenging, especially during pregnancy. Epilepsy is just as prevalent in women as in men, but physicians must exercise special care when treating pregnant women because some anti-seizure medications raise the risk of fetal malformations. They must also monitor the dosage of anti-seizure medications, because women metabolize the drugs differently during pregnancy and may suffer breakthrough seizures.
She added that pregnancy can have a lasting impact on women’s risk of neurological disease.
“Gestational hypertension, diabetes and preeclampsia can produce a higher risk of stroke and cognitive issues decades down the line,” O’Neal said. “Managing these risk factors can prevent these complications.”
Stroke offers a useful example of how risks may differ between women and men, O’Neal said. Cerebral aneurysms occur more often in women. The risk of subarachnoid hemorrhage is higher. Pregnancy, a hypercoagulable state, raises a woman’s risk of stroke caused by a blood clot. Migraine with aura influences stroke risk, as do estrogen-based contraceptives.
“When you look at any neurological disease, you find many factors that are different in women than men,” she said. “Some are related to biology, others to how they get care.”
Neurological diseases affect women differently over the long term too, she said. “Women who have stroke [experience] more disability than men, partly because they live longer, partly because they suffer from more depression.”
“There are differences,” O’Neal said, “in almost every single neurological disorder.”