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Office of Research on Women’s Health (ORWH)

A to Z Guide: Sex and Gender Influences on Health

Research on sex and gender differences — research that spans basic studies on cells to large, clinical trials involving thousands of patients — aims to understand health differences between males and females at all levels. The knowledge will improve health for both women and men. Get the facts here about how sex and gender influences health and disease.

A to Z Vocabulary Index

A

Alcohol UseArrhythmias

Alcohol Use

Drinking alcohol is a common activity in most cultures around the world, for both women and men. However, while drinking in moderation may be considered generally safe, alcohol abuse poses many risks to a woman’s health. For example, although men are more likely to drink alcohol than are women, and men often drink more and more frequently, women are more vulnerable to some of alcohol’s harmful effects. These effects are based on both gender– and sex–based factors, and they include differences in metabolism. In addition, alcohol use by women is also linked to many other physical and psychosocial health issues, such as unprotected sex, illicit drug use, and intimate partner violence. Here are some of the facts about women and alcohol use.

  • Moderate, or low-risk, drinking for women is defined as no more than three drinks on any single day and no more than seven drinks per week.
  • Low to moderate alcohol consumption in women, defined as fewer than three drinks per day, increases the risk of certain cancers, including breast cancer.
  • After drinking similar amounts, women have higher blood levels of ethanol than do men, and women are more susceptible to alcoholic liver disease such as hepatitis.
  • A woman’s moderate alcohol intake may reduce her coronary heart disease risk, although details remain unclear.
  • Research showed that female college-student drinkers exceeded NIH-defined guidelines for weekly drinking more frequently than did their male counterparts, which may have long-term consequences on drinking behavior in these women.
  • The drug naltrexone is used to treat alcohol dependence, but it does not work for everyone. A small study showed that naltrexone worked better in women to reduce alcohol’s positive subjective effects, suggesting it may be useful in therapy for alcohol dependence in women.
  • Research with the model organism Drosophila (fruit flies) showed that female fruit flies are more prone to the sedative effects of alcohol than are male flies.
  • No amount of drinking during pregnancy is safe. However, 20 to 30 percent of women drink at some time during pregnancy, which includes the period of time before a woman knows she is pregnant.

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Arrhythmias

As an electrically controlled organ, the heart beats when a wave of electricity courses through heart muscle in a defined regular path. Any disruption of this path of conduction, called an arrhythmia, causes the heart to beat irregularly. An arrhythmia can be very mild, even undetectable, or serious and fatal. Sex and gender differences are known to affect heart rhythms. Here are some examples.

  • Certain medications, including the allergy drug Seldane and the gastrointestinal drug Propulsid (both of which have been taken off the market in the United States) trigger a potentially fatal heart arrhythmia more often in women than in men.
  • A 2009 study showed that women are more likely than men to have complications from implantable cardiac defibrillators, devices that monitor heart rhythms and deliver shocks when needed to restore a normal heartbeat.
  • Although men are more likely than women to experience a usually mild condition known as atrial flutter (heart palpitations), surgical treatment (ablation) of this arrhythmia affects women and men differently, according to a 2013 study. Although less women than men are treated with ablation, women are more likely to experience surgical complications and also more likely to have atrial flutter after the surgery.

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C

CancerCardiovascular Risk

Cancer

Cancer is often called a disease of DNA, since tumors develop when cells divide uncontrollably, and in many cases DNA mutations that affect the copying of DNA are to blame. Researchers today know, however, that cancers are very different from each other – almost different enough to look like a completely different health condition. In addition, as scientists learn more about the molecular roots of disease, they can classify cancers based upon molecular signatures. These signatures can aid in diagnosis, treatment, and prognosis. In addition to being different from one another the same type of cancer can be quite different in females and males. Here are a few examples.

  • Between 2001 and 2010, prostate cancer was the most common cancer diagnosed among U.S. men of all races and ethnic groups.
  • The most common cancer diagnosed among U.S. women was breast cancer, but lung cancer is the leading cause of death among cancers in women of all races and ethnic groups except Hispanic women, for which breast cancer is the leading killer in U.S. women.
  • Some studies suggest that female cancer patients are more likely to experience inadequate pain management than male patients, but more studies are needed.
  • Research comparing cell lines from women to cell lines from men reported sex differences in DNA damage to cancer-causing chemicals in tobacco smoke. For a given number of cigarettes smoked, females appear to be at higher risk of developing lung cancer than males.
  • Females are less prone to liver cancer than males (humans and mice given a liver carcinogen), possibly due to estrogen’s protective effect against inflammation in the liver.

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Cardiovascular Risk

For the most part, an individual has direct control over whether he or she will develop heart disease, by managing behaviors that raise or reduce the chances that heart disease will take root in their body. NIH-funded medical research that goes back decades has defined a core set of cardiovascular risk factors that individuals can manage with the help of a doctor. The risk factors include smoking, high cholesterol and triglycerides, high blood pressure, diabetes, and being overweight or obese.

Yet, even though everyone should pay attention to these risk factors that affect heart health, the risks differ between women and men in various ways that appear subtle, but can be very significant.

  • In women, aspirin reduces risk of ischemic stroke, whereas in men, low-dose aspirin therapy reduces risk of heart attack.
  • Cholesterol plaque in women may not build up into major artery blockages, but instead spreads evenly throughout the artery wall. This means that artery blockages can be more difficult to diagnose in women, who may not have outright symptoms but are still at high risk for heart attack.
  • Cholesterol levels vary over the course of a woman’s menstrual cycle.

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D

Depression

Gender plays an important role in mental health disorders like depression, which is common but underdiagnosed. Epidemiological research shows that females are more likely than males to develop not only depression, but also eating disorders, panic disorder, and post-traumatic stress disorder. Here are some sobering facts about depression in women:

  • Depression is the leading cause of disability in the United States for individuals 15-44 years of age.
  • Depression is the 5th most common source of disability worldwide for women, and it is predicted to be the second leading cause of global disability by 2020.
  • Some diseases, including epilepsy, Alzheimer’s disease, cancer, and cardiovascular disease, can bring on depression in one sex but not the other.
  • Depressed middle-aged women have almost double the risk of having a stroke.

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H

Health CareHeart Attacks

Health Care

Women and men have different health care habit and needs, both of which affect health in significant ways. Women are more likely to be the primary family caregiver, meaning their decisions affect the health of children and men in the household as well. Over the course of a woman’s lifetime, due in part to reproductive health issues, she relies on the health care system more than her male peers. Recent studies have shown other specific examples of health care gender differences.

  • 2012 study showed that women are more likely than men to defer seeing their doctor(s) or dentist, or fill a prescription, because they could not afford the cost.
  • Women who have a heart attack are much more likely (57%) than men having a heart attack (28%) to call 9-1-1 for help. However, this 2013 study also revealed no difference in calling behavior among men and women with response to chest pain alone.

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Heart Attacks

Heart attacks are a leading killer of people all over the world. Heart attacks occur when heart muscle is deprived of oxygen-rich blood. Although heart disease affects both women and men, many women remain unaware that they are at risk. Moreover, many aspects of heart disease differ between women and men. Here are some of the ways.

  • Women often have early symptoms within the weeks prior to their heart attack — unusual fatigue, sleep disturbance, but not always chest pain or discomfort.
  • At the time of their heart attack, women have shortness of breath, weakness, and fatigue — but not always chest pressure, pain, or tightness.
  • In 2012, 56 percent of all women said they know heart disease as their number-one killer.
    • But… only 36 percent of black women and 34 percent of Hispanic women said they know heart disease as their number-one killer.
    • And… young women (25 to 34) remain least aware: only 44 percent said they know heart disease as their number-one killer.

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I

Influenza

Influenza, more commonly called the flu, is a viral infection of the nose, throat, and lungs. Flu symptoms may include muscle aches, chills, cough, fever, headache, and sore throat. Research is underway to find out why the flu virus and vaccine affect men and women differently. For example, women are more likely than men to have severe flu symptoms. Here are some facts about men and women and the flu:

  • Pregnant women who get the flu are more likely than women who are not pregnant to become very ill and have to go to the hospital. For this reason, doctors recommend that most pregnant women should get a flu shot.
  • Women who get a half dose of the flu vaccine produce as many antibodies as men who receive a full dose.
  • Men with high levels of testosterone produce fewer antibodies in response to the flu vaccine compared with men with low testosterone.
  • The immune systems of female mice respond to the flu virus with a much stronger counterattack, known as an inflammatory response, compared with male mice.
  • When female mice are given estrogen, they have less inflammation and milder flu symptoms.

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J

Joints

Sex-specific research analyses are especially important in orthopedics because of the substantial sex-based anatomical differences between females and males. Researchers are beginning to appreciate that structural differences of the knee joint and thigh muscles, differences in the ways male and female athletes move, and other sex differences help explain why women are often more susceptible to certain injuries than men. Here are some examples of sex-based factors that affect the health of joints:

  • Females are two to three times more likely than males to develop patellofemoral pain syndrome, one of the most common causes of knee pain in teen and young-adult athletes.
  • Tears of the anterior cruciate ligament (ACL), the ligament that runs through the front of the knee, are more common in females than in males.
  • Temporomandibular joint and muscle disorder-type pain is 2.25 times more prevalent in women than in men
  • Among people undergoing total hip replacement, women were 29 percent more likely than men to require repeat surgery within the first three years.
  • Female college athletes have the highest risk of having a first-time noncontact ACL injury among female and male athletes in high school and college. (Noncontact injuries are caused by a person’s own actions, such as landing after a jump or coming to an abrupt stop while running.)
  • Women use their hamstring and quadriceps muscles differently from men when they are running and cutting from side to side during sports activities, and this puts greater stress on the knee.

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L

Lupus

Lupus is an autoimmune condition that causes inflammation and damage to various organs. Common symptoms include extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes, hair loss, and kidney problems. Lupus develops slowly, with symptoms that come and go. The most common type, systemic lupus erythematosus, usually appears in the mid-teens, 30s or 40s. Women are more likely to get lupus than men, and African-American, Hispanic, Asian, and American Indian women have a higher lupus risk than white women. Here are examples of how lupus can differ in women and men:

  • Although more women than men get lupus and a related disorder, systemic sclerosis, men are more likely to have more severe disease.
  • In contrast, women are more likely than men to develop lupus-related urinary tract infections, hypothyroidism, depression, esophageal reflux, asthma, and fibromyalgia.
  • Among children and adults with lupus, males are at greater risk than females for kidney injury, kidney failure, and kidney-related death.
  • Researchers have found a lupus-related gene (called IRAK1) on the X chromosome, which may help explain why women get the disease more often than men.
  • Sex hormones may also have a role in making women more likely to develop lupus.

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M

Men’s Health

As is the case with women’s health, many people tend to think of men’s health as it relates to the reproductive organs. However, just as in women’s health, men’s health is much broader. While many sex-based influences affect diseases/organs related to reproduction, such as prostate and testicular cancer, many sex-based factors influence diseases and organs unrelated to reproduction. Here are a few examples.

  • Osteoporotic fractures in men over 50 are common, yet they are under-recognized and often undertreated.
  • Systemic lupus erythematosus, or lupus, is often thought of as a women’s disease, yet this condition affects men too. What’s more, males with lupus often have more severe disease than females, and they are more likely than females to experience lupus-related kidney failure.
  • White male teens and young adults are 55 percent more likely to die of melanoma, the most serious type of skin cancer, than their female peers of the same age.
  • Onchocerciasis, the second leading cause of infectious blindness in the world, is more common in men, who work in contaminated rivers in the developing world. Onchocerciasis is thus an example of a gender-based health disparity, since it is caused by a behavior more common to males in certain societies, although it is treatable with antibiotics.

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O

Osteoarthritis

Osteoarthritis is a condition that accompanies aging, as the body’s bones and joints suffer wear and tear with time and lots of use. It is painful, and there is no cure. What’s more, osteoarthritis remains the leading cause of chronic disability in the United States, and it disproportionately affects post-menopausal women. Current treatment generally involves a mix of exercise, lifestyle modification (such as weight loss), and pain relievers. Researchers are hard at work looking for new clues about how to prevent and treat osteoarthritis. It is more common among women than men in every age group, but there are subtle differences worth knowing about.

  • The severity of osteoarthritis is usually significantly worse in women than it is in men.
  • In women, osteoarthritis typically affects certain joints such as the knees, hips, and/or hands.
  • Before age 45, more men than women have osteoarthritis, but after age 45, the condition is more common in women.
  • Black women are at greater risk than white women for developing osteoarthritis and for experiencing complications from the condition.
  • Black women and black men with osteoarthritis are much less likely to undergo total knee replacement when compared to white men.
  • ORWH was one of the co-founders of the Osteoarthritis Initiative, a longstanding, large, multi-center prospective clinical study of osteoarthritis of the knee. It involves researchers from other NIH components such as the National Institute of Arthritis and Musculoskeletal Diseases and the National Institute on Aging, universities, and the private sector. All the data is publicly available online. The Osteoarthritis Initiative has prompted many additional NIH-funded research studies that are ongoing.

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P

PainPrescription Painkiller Abuse

Pain

The sensation of pain is a protective response that alerts us when we are hurt or sick. Pain can be caused by injury to a specific area of the body, or it can be caused by an illness, such as the flu, that makes the whole body ache. Pain may be dull or intense; it may be constant; or it may come and go. Sometimes the cause of the pain is unknown. Women seem to be more sensitive to pain than men. Here are some other examples of how pain is different in women and men.

  • Several studies show that chronic pain is more common in women than men.
  • Women experience pain from musculoskeletal, neuropathic, abdominal, and migraine-related conditions more often than men do.
  • Migraines are twice as common in females as in males, and the brain is affected differently in females compared with males.
  • Among individuals with depression, women are more likely to report pain complaints than men.
  • In imaging tests of people with irritable bowel syndrome, brain regions that control emotions were more active in female brains, and cognitive regions were more active in male brains.
  • Researchers have identified a molecular pain pathway that operates only in the spinal cords of male mice.

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Prescription Painkiller Abuse

Women in America are dying from prescriptio-drug overdoses at unprecedented rates. Most of these deaths are caused by opioids, painkillers that are chemically similar to heroin and that have similar effects in the body and can be highly addictive. Examples include OxyContin, Percocet, and Vicodin. Research has shown that males and females do not respond in similar ways to opioids. Here are some facts about sex- and gender-based difference in prescription painkiller abuse.

  • Overall, men are more likely to die of a prescription painkiller overdose than women; however, since 1999, the percentage increase in deaths has been greater among women (400 percent in women compared to 265 percent in men).
  • For every woman who dies of a prescription painkiller overdose, 30 go to the emergency department for painkiller misuse or abuse.
  • According to the Centers for Disease Control and Prevention, the majority of people, both women and men, who misused prescription pain relievers (55 percent) received them free from a friend or relative, 17 percent got them using a doctor’s prescription, 4 percent bought them from a drug dealer, and a small fraction (less than a half-percent) ordered them online.
  • Animal studies showed that males and females have different physiological responses to coping with opioid withdrawal, suggesting the need for gender-appropriate addiction-treatment strategies.
  • Studies show that overall, women and men have similar perception of pain, but that pain perception varies significantly by trigger, such as cold, hot, pressure, ischemia[RH1], or other sensation.
  • Use of opioid drugs during pregnancy can produce drug-withdrawal syndrome in newborns. The proportion of babies born with this health burden tripled from 2000 to 2009.

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S

SmokingStem CellsStroke

Smoking

Tobacco use is the leading cause of preventable disease and death in the United States and worldwide it carries a substantial health burden. Smoking is an unhealthy habit for both genders, but women and men experience different health risks, and they respond differently to techniques designed to help them quit. Here are some examples:

  • Quitting smoking at any age dramatically cuts a woman’s risk of death.
  • Women smokers have a higher breast cancer risk.
  • Women smokers who use oral contraceptives risk serious health effects such as blood clots, heart attacks, and strokes.
  • Smoking affects a woman’s eyes, putting her at higher risk for vision problems, such as macular degeneration and cataracts, later in life.
  • There is a strong relationship between the number of cigarettes a young woman smokes per day and the probability that she will have an ischemic stroke.

Quitting smoking is one of the best decisions a woman can make toward a healthier tomorrow for herself and her family.

  • While men are more sensitive than women to nicotine’s effects on the body, women are more susceptible than men to smoking sensory triggers like smell and taste, as well as to social cues.
  • Nicotine patches and gums don’t work as well in women as they do in men.
  • Quitting techniques that work better in women than in men include cognitive–behavioral therapy that focuses not only on quitting smoking but also on related issues such as controlling quitting-associated weight gain and moderating mood

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Stem Cells

Muscle-derived stem cells, which reside in skeletal muscle tissue, are one type of adult stem cell. Hematopoietic stem cells, in bone marrow, are another. Because stem cells are not yet specialized, they can turn into other many different types of cells, such as bone, fat, and blood.

All cells, not just stem cells, have a sex. Each cell in the body is either male or female, based on its DNA content contributed by XX (female) and XY (male) chromosomes. Other factors contribute as well, such as the source (maternal or paternal) of the X chromosome, and various other biological signatures. Here are some examples of how sex affects stem cells:

  • Cell sex exerts a strong effect on the regenerative capacity of muscle-derived stem cells.
  • In mice, stem cells that mature to become blood cells divide faster in females than in males.
  • Hormones affect growth of stem cells in the mammary gland.

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Stroke

A stroke is sort of like a heart attack in the brain. Strokes occur when blood flow to a part of the brain suddenly stops, starving brain cells of the oxygen they need to live. Clogged arteries can cause a so-called ischemic stroke, in which fat and cholesterol form plaques in artery walls, allowing less blood to flow through freely.

While some of the risk factors for stroke are the same in men and women – such as family history of stroke, high blood pressure or cholesterol, smoking, and being overweight – certain aspects of stroke are unique to women. Researchers have identified several sex/gender differences, such as these:

  • While men have a higher risk of stroke than women in general, women are usually older when they have strokes, and they are more likely to die of strokes than men.
  • Women have a poorer quality of life after a stroke than men.
  • Women with a history of preeclampsia during pregnancy are 60 percent more likely to have a non-pregnancy-related stroke later in life.
  • Women who suffer from migraines with visual components like flashing lights have a higher risk of having an ischemic stroke.

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T

Telomeres

Made of DNA, telomeres resemble shoelace tips and serve a similar function. Telomeres are tiny pieces of DNA capping the very ends of our chromosomes. As cells divide normally throughout our lives, each DNA-containing chromosome must be copied, and the tips of stringy chromosomes are particularly vulnerable to damage, much like an actual shoestring can be physically damaged by dragging across the ground.

Thus, telomeres protect our genes by taking a hit themselves – they are known to become frayed and shorter as our cells divide many times throughout life. Scientists are learning that shorter telomeres also show up along with certain diseases, like atherosclerosis and some types of cancer. They suspect that shorter telomeres also compromise the health of cells in blood vessels, which may set the stage for clots to form, stick, and block blood flow.

As reported in a 2011 study, scientists conducting the Cardiovascular Health Study learned that certain telomere-associated molecular changes were linked with higher risk of death from cardiovascular disease in Caucasian women. These findings suggest that short telomeres might be a tool for predicting or monitoring heart disease in some women.

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V

Vision

Vision disorders affect women disproportionately both in the United States and throughout the world. But in addition to affecting vision, eye changes can signal the presence of other conditions, especially autoimmune diseases like lupus and rheumatoid arthritis. Ocular manifestations of thyroid disease may be the first characteristic symptom that brings a woman to a physician’s office to seek treatment. Here are some examples of how vision disorders affect women and men:

  • Dry eye affects twice as many women than men over 50 years of age. Dry eye disease affects quality of life – interfering with routine activities such as reading, working on a computer, and driving a car.
  • Cataracts that cloud the eye’s lens are more likely to occur in women than in men. In developing countries, women are less likely than men to receive cataract surgery.
  • Brain-imaging studies of people with migraines – intense headaches that are twice as common in women than men and that often affect vision – have reported sex-specific patterns.
  • Adult women experience about 25 percent more uncorrected visual impairment due to refractive error – which impedes the ability to focus – compared to adult men.
  • Worldwide, women account for two-thirds of all people with blindness or visual impairment, but more than three-quarters of these vision problems are preventable.

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This page last reviewed on December 10, 2014

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