Precision Medicine Should Include Sex And Gender In Decision-Making

Precision medicine should incorporate sex and gender in decision-making in order to optimize care for each patient, according to a review.

"First, there needs to be a recognition and an understanding amongst clinicians regarding the biological differences between men and women that affect all organ systems," Dr. Deborah Bartz from Brigham and Women's Hospital and Harvard Medical School in Boston told Reuters Health by email. "Second, clinicians should take these differences into account when they see individual patients. Ultimately, this is the process of applying precision medicine into the clinical exam room."

Dr. Bartz and colleagues propose eight key domains within sex- and gender-informed medicine in their online report in JAMA Internal Medicine: genetics, epigenomic modifiers, hormonal milieu, immune function, neurocognitive aging process, vascular health, response to therapeutics, and interaction with healthcare systems.

For each, they review clinical examples that highlight sex and gender differences.

Immune function, for example, differs between sexes and by gender-specific exposures and likely accounts for the striking female preponderance of most autoimmune diseases.

The aging process also differs significantly, with women developing Alzheimer disease at almost twice the rate of men, regardless of age.

Many cardiovascular risk factors are more prevalent in women, including physical inactivity, obesity, depression, history of sexual abuse, and hypertension at older age, whereas others, including dyslipidemia, are more common in men.

These and other gender-specific experiences can be associated with disparities in disease burden through differences in prevention, treatment referral patterns, and medication use, and such disparities are exacerbated further in transgender and gender-nonconforming patients.

"Basic science, social science, and clinical research demonstrate wide variability between men and women in disease risk, presentation, and prognosis, along the parameters of biologic sex and sociocultural gender," Dr. Bartz said. "Despite this evidence, sex and gender remain inadequately considered in medical decision-making, resulting in poorer health outcomes. These health outcome disparities are compounded in communities with further layering of disadvantage, such as among women of color, women of low socioeconomic status, and women with disability."

"Considering a patient's biological sex and sociocultural gender will enable physicians to make more informed clinical decisions that will improve health outcomes for all patients," she said.

"Probably the best clinical outcomes come from those patient-doctor relationships that are embedded in open communication, lack of power differentials, and lack of mistrust in the patient-physician dyad," Dr. Bartz said. "However, probably the best advice for a patient who is seeking out the best possible care specific to her as a woman is to make sure she has a positive relationship with her physician that allows her to feel the agency or self-determination to speak freely, and to ask questions, specifically about the medical literature regarding sex- and gender-based differences."

Dr. Marianne J. Legato, Emeritus Professor of Clinical Medicine, Columbia University, New York, who has researched various aspects of gender-specific medicine, told Reuters Health by email, "We are rapidly seeking—and finding—sex/gender specific characteristics at all levels of human physiology, particularly at the genomic and epigenetic level. Genomic scientists have to be urged, just as we urged clinicians 3 decades ago when the topic of gender-specific medicine was first introduced, to look for sex/gender-specific features of their findings."

"A careful look at the impact of sex/gender on data at the molecular level still needs to be reinforced and requests to investigators for the sex/gender specific aspects of their results have to be made constantly (sometimes with much less effect than we hope)," she said.

"One of the most important issues in our current thinking is the persistent effort to separate the concepts of biological sex and gender," she said. "Sex and gender are actually a single entity at the molecular level; epigenetic influences modify the phenome, essentially translating the impact of the environment on genetic expression. I think that as our understanding of the comprehensive physiology of epigenetics continues to expand, more investigators will regard the two contributions as a unified whole or at least as inseparable."

"The tabulation, testing, and teaching of gender-specific aspects of individual personal care is what we hope for," Dr. Legato said. "We are far from the application of what is essentially very new science, propelled by very new techniques, to the care of the patient at the bedside."

Dr. Christian Delles from University of Glasgow, UK, who recently reviewed precision medicine and personalized medicine in cardiovascular disease, told Reuters Health by email, "We need to understand the mechanisms that relate sex and gender with disease. The article nicely outlines that this is far more than just simple genetic factors or sex hormones: it involves, for example, different environmental exposures and lifestyle that can be very different between men and women and affects complex systems such as the immune system."

"Looking at sex and gender is not only important for clinical care but also provides an opportunity to better understand disease mechanisms and defines new research avenues," Dr. Delles said in an email. "We may have missed such opportunities in the past, but this and other articles in this field show the great potential that research into sex and gender effects can have."

—Will Boggs MD

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