Neurology Now: June/July 2017 - Volume 13 - Issue 3 - p 36–41
doi: 10.1097/01.NNN.0000520751.14042.c4
Features: Sex-Specific Medicine
That reality has contributed to sex-specific approaches to diagnosis, treatment, and management.
Women comprise more than half the population in the United States, but until somewhat recently, they weren't routinely included in clinical trials or other medical research. That changed in 1994, when Congress mandated that scientists begin including women in their studies as a matter of course, says Marianne J. Legato, MD, PhD, founder and director of the Foundation for Gender-Specific Medicine (http://gendermed.org) and emerita professor of clinical medicine at Columbia University in New York. Historically, scientists believed that studying male subjects served just as well as including both sexes, says Dr. Legato, “but that isn't always true.”
A DIFFERENT LENS
The idea of studying biological sex as it relates to various diseases has gained recognition in the last two decades, thanks to several trends. In 2001, for example, in a report from the Institute of Medicine titled Exploring the Biological Contributions of Human Health: Does Sex Matter? researchers noted that every cell has a sex, and that sex differences start in the womb and continue throughout life. In 2006, two gender-specific organizations were established—Dr. Legato's foundation and the International Society for Gender Medicine—to promote collaboration among scientists throughout the world to study the ways in which sex affects normal function as well as various diseases. Then in 2016 the National Institutes of Health introduced a policy requiring all scientists requesting funding for research to consider the role of sex as a variable in studies involving cells, animals, and humans.
Noteworthy differences in risk factors, symptoms, and disease progression exist between women and men with many conditions, including cardiovascular disease, type 2 diabetes, and neurologic disorders, says Dr. Legato. “Many diseases are multifactorial at the genetic level, and how genes are expressed is profoundly influenced by sex,” she explains. Scientists continue to gain a better understanding of the anatomical, neurologic, chemical, and functional differences in how various medical conditions affect women versus men, which will lead to improved diagnosis and treatment.
We look at how six neurologic conditions—Alzheimer's disease, epilepsy, migraine, multiple sclerosis (MS), Parkinson's disease, and stroke—manifest in women, and how that influences their diagnosis, symptoms, medication, and prognosis.
PARKINSON'S DISEASE
STATISTICS: Men are one and a half times more likely to be diagnosed with Parkinson's disease than women, according to the Parkinson's Foundation. Women also tend to be diagnosed much later, long after symptoms are present.
DIAGNOSIS: Because more men than women are diagnosed with Parkinson's disease, primary care doctors are less likely to consider it in women who have the symptoms, says Maria De Leon, MD, a neurologist and movement disorders specialist in Nacogdoches, TX, who has Parkinson's disease herself. She's also a research advocate for the Parkinson's Foundation. In 2010, Robin Morgan, an award-winning feminist writer and activist in New York City, was diagnosed with Parkinson's disease after being misdiagnosed for a year and a half. She was quite sure the tremor in her hands was a sign of Parkinson's, given that her mother had the disease, but her doctor dismissed the possibility. Still, she considers herself fortunate because, she says, “I know women who've waited seven years for a diagnosis.” To raise awareness of sex and gender differences in Parkinson's disease and to encourage research into women-specific issues, the Parkinson's Disease Foundation—a forerunner to the Parkinson's Foundation—launched the Women and PD Initiative in 2015.
SYMPTOMS: “Women present more with affective disorders [such as depression], cognitive changes, fatigue, and stiffness—not the tremors people recognize [as a hallmark of Parkinson's disease],” Dr. De Leon says. “Women have better survival rates, but they turn out to be more disabled and have a lower quality of life,” says Allison Willis, MD, assistant professor of neurology and biostatistics and epidemiology at the University of Pennsylvania School of Medicine in Philadelphia.
MEDICATIONS: Some drugs prescribed for Parkinson's disease can cause bones to thin, which may heighten the chance of developing osteoporosis, especially for women who are already at risk for it. Women may also be more vulnerable to side effects—such as nausea, sleepiness, dizziness, and headaches—than men, Dr. De Leon says. As a result, women may need lower doses or more time to adjust to the drugs.
HORMONES: Estrogen, a predominantly female hormone, has a somewhat protective effect. Researchers believe it may inhibit inflammation, which is common in Parkinson's disease. Or the hormone may increase the release and expression of growth factors in the cells surrounding neurons that are responsible for ensuring and maintaining the survival of those neurons, Dr. De Leon says. Either theory may explain why the risk of developing Parkinson's disease increases after menopause when estrogen levels drop significantly. It may also explain why “women who have induced menopause—their ovaries are removed early—have the same incidence of Parkinson's disease as men,” Dr. Willis says.
MENSTRUAL CYCLE: Younger women who have Parkinson's disease face a vicious cycle when it comes to menstruation. “Parkinson's disease makes periods worse—longer, heavier, and sometimes more painful—and periods can make Parkinson's symptoms worse,” says Dr. De Leon. “Parkinson's medications can also influence the menstrual cycle, making periods irregular.”
BIRTH CONTROL PILLS: The effects of birth control pills aren't well established, but since hormonal fluctuations affect symptoms, using birth control pills to shorten the length and lessen the severity of periods might help manage symptoms, Dr. De Leon says.
PREGNANCY: Several reports of successful pregnancies in women with Parkinson's disease have been published, but medications need to be chosen carefully during pregnancy. Levodopa has been shown to be safe, but some medications for Parkinson's disease can cause birth defects if they're taken during pregnancy.
ALZHEIMER'S DISEASE
Statistics: Women make up nearly two-thirds of those who have Alzheimer's disease, according to the Alzheimer's Association.
DIAGNOSIS: After age 70, women with Alzheimer's disease are diagnosed sooner than men. Because many women continue to manage the household, including doing the cooking and grocery shopping, and stay involved in community-related activities such as volunteering, their declines in functionality may be more noticeable, says Douglas W. Scharre, MD, director of the division of cognitive neurology at Ohio State University. By contrast, “after they retire, some men don't stay as active [in different areas of their lives], so we can't tell as readily if their functional status is affected.”
SYMPTOMS: Symptoms are similar in both sexes and typically include short-term memory loss, forgetfulness, repeating questions, misplacing items, and forgetting conversations.
MEDICATIONS: Some women may experience more gastro-intestinal side effects from certain medications for Alzheimer's disease, such as donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), Dr. Scharre notes. After being diagnosed with early-stage Alzheimer's disease in 2013, Carol Poole, of Rockledge, FL, had trouble adjusting to her medication and had to increase her dosage gradually. “I'd get side effects like dizziness, an upset stomach, or fatigue, and sometimes I'd forget to take it,” she admits, which meant the adjustment process would start over again.
HORMONES: Estrogen may have a protective effect against Alzheimer's disease. As in Parkinson's, estrogen may inhibit inflammation, which is also common in Alzheimer's disease. Or the hormone may “increase the release and expression of growth factors in glial cells [which surround neurons] that are responsible for ensuring and maintaining the survival of neurons,” says Dr. De Leon. Either theory may explain why the risk of developing Alzheimer's disease increases after menopause when estrogen levels drop significantly. However, the effectiveness of estrogen therapy for minimizing the risk of Alzheimer's disease after menopause has shown mixed results, says Jennifer Rose Molano, MD, FAAN, associate professor of neurology at the University of Cincinnati Academic Health Center.
MENSTRUAL CYCLE/BIRTH CONTROL PILLS/PREGNANCY: “Less than 3 percent of patients develop Alzheimer's disease before age 65,” so little is known about the effects of the menstrual cycle, birth control pills, or pregnancy on early-onset Alzheimer's, Dr. Scharre says.
http://journals.lww.com/neurologynow/pages/articleviewer.aspx?article=00017&issue=13030&type=FullText&year=2017
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