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.
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.
- Moderate alcohol intake and cancer incidence in women (Journal of the National Cancer Institute)
- High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism (New England Journal of Medicine)
- Prospective study of alcohol drinking patterns and coronary heart disease in women and men (British Medical Journal)
- Sex differences in college student adherence to NIAAA drinking guidelines (Alcoholism, Clinical and Experimental Research)
- The effect of naltrexone on alcohol’s stimulant properties and self-administration behavior in social drinkers: influence of gender and genotype (Alcoholism, Clinical and Experimental Research)
- Acute ethanol responses in Drosophila are sexually dimorphic (Proceedings of the National Academies of Sciences)
- Fact Sheets: Excessive Alcohol Use and Risks to Women’s Health (Centers for Disease Control and Prevention)
- Women and Alcohol (National Institute on Alcohol Abuse and Alcoholism)
- Rethinking Drinking (NIAAA)
- Fetal Alcohol Syndrome Disorders (MedlinePlus)
- Fetal Alcohol Exposure (NIAAA)
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.
- MedlinePlus: Pacemakers and Implantable Defibrillators
- Gender differences in procedure-related adverse events in patients receiving implantable cardioverter-defibrillator therapy
- Sex-related differences in peri- and post-ablation clinical data for patients with atrial flutter
- Female gender as a risk factor for drug-induced cardiac arrhythmias: evaluation of clinical and experimental evidence
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.
- 2013 Annual Report to the Nation on the Status of Cancer
(National Cancer Institute – statistics)
- Cancer Among Women
(Centers for Disease Control – statistics)
- Women’s Cancers
(National Cancer Institute – research, treatment information)
- Pain and its treatment in outpatients with metastatic cancer
(New England Journal of Medicine)
- Differences in lung cancer risk between men and women: examination of the evidence
(Journal of the National Cancer Institute)
- Sex differences in susceptibility to PAHs is an intrinsic property of human lung adenocarcinoma cells
- Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production
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.
- A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women
- Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men: A Sex-Specific Meta-analysis of Randomized Controlled Trials
- A longitudinal study of serum lipoproteins in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study
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.
- Gender and women’s mental health: World Health Organization.
- Institute for Health Metrics and Evaluation: Global Burden of Disease Study 2010.
- Not all depression is created equal: sex interacts with disease to precipitate depression.
- Depression and risk of stroke in midaged women: a prospective longitudinal study.
- Depression: Medline Plus
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.
- Gender differences in financial barriers to primary health care in New Zealand
- Gender differences in calls to 9-1-1 during an acute coronary syndrome
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.
- National Heart, Lung, and Blood Institute’s “What Are the Signs and Symptoms of Heart Disease?”
- Gallup poll on women’s emotional health after heart attack
- Fifteen-Year Trends in Awareness of Heart Disease in Women: Results of a 2012 American Heart Association National Survey
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 explain why women are often more susceptible to injuries than men. Here are some examples of sex-based differences 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, a 2010 study reports.
- Anterior cruciate ligament (ACL) tears are more common in females than in males — this is thought to be due in part to hormones, but other sex-based differences also appear to play a role.
- Temporomandibular joint and muscle disorder (TJMD)-type pain is 2.25 times more prevalent in women than in men.
- As reported in a 2013 study, among people undergoing total hip replacement, women were 29 percent more likely than men to require repeat surgery within the first three years.
- The incidence and potential pathomechanics of patellofemoral pain in female athletes.
- Understanding and preventing noncontact anterior cruciate ligament injuries: a review of the Hunt Valley II meeting, January 2005.
- Temporomandibular joint and muscle disorder-type pain in U.S. adults: the National Health Interview Survey.
- Sex and risk of hip implant failure: assessing total hip arthroplasty outcomes in the United States.
- TMJ Disorders: Medline Plus.
- Anterior cruciate ligament (ACL) injury: Medline Plus.
- Hip replacement tutorial: Medline Plus.
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.
- Men’s Health (MedlinePlus)
- Osteoporosis in men (Nature Reviews in Endocrinology)
- Osteoporosis in Men (NIH Osteoporosis and Bone Diseases National Resource Center)
- Gender differences in the pathogenesis and outcome of lupus and of lupus nephritis (Clinical and Developmental Immunology)
- Lupus (MedlinePlus)
- Melanoma survival disadvantage in young, non-Hispanic white males compared with females (JAMA Dermatology)
- Melanoma (MedlinePlus)
- African programme for onchocerciasis control 1995–2015: Model-estimated health impact and cost (PLoS Neglected Tropical Diseases)
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.
- Osteoarthritis (MedlinePlus)
- Chronic Disease Prevention and Health Promotion: Arthritis (Centers for Disease Control and Prevention)
- Race, sex, and total knee replacement consideration: role of social support (Arthritis Care Research)
- Osteoarthritis Initiative (NIAMS)
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.
- Vital Signs: Prescription Painkiller Overdoses (Centers for Disease Control and Prevention)
- Chronic pain treatment and addiction (National Institute on Drug Abuse)
- Prescription Drug Abuse (MedlinePlus)
- Addressing the Needs of Women and Girls: Developing Core Competencies for Mental Health and Substance Abuse Service Professionals (Substance Abuse and Mental Health Services Administration)
- Gender effects on drug use, abuse, and dependence: a special analysis of results from the National Survey on Drug Use and Health (Gender Medicine)
- Results from the 2010 National Survey on Drug Use and Health (SAMHSA)
- Nonmedical Use of Prescription Drugs (The American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women)
- Pleiotropic opioid regulation of spinal endomorphin 2 release and its adaptations to opioid withdrawal are sexually dimorphic (Journal of Pharmacology and Experimental Therapeutics)
- Sex differences in pain: a brief review of clinical and experimental findings (British Journal of Anaesthesiology)
- Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009 (Journal of the American Medical Association)
- Neonatal abstinence syndrome (MedlinePlus)
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
- 50-year trends in smoking-related mortality in the United States.
- Cohort study of risk factors for breast cancer in post menopausal women.
- Active smoking and breast cancer risk: original cohort data and meta-analysis.
- Combined oral contraceptives, smoking, and cardiovascular risk.
- Women’s Eye Health.org.
- Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women.
- Gender differences in smoking: National Institute on Drug Abuse.
Did you know that every cell has 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 molecular “sex” signatures.
Researchers have just begun to scratch the surface to learn more, but a 2007 study in mice showed that cell sex exerts a strong effect on the regenerative capacity of muscle-derived stem cells.
Muscle-derived stem cells, which reside in skeletal muscle tissue, are one type of adult stem cells. These cells are not yet specialized, and can turn into not only muscle but also bone, fat, and some types of blood cells. The ability to turn muscle-derived stem cells into muscle exclusively, on purpose, could be very important for treating a range of health conditions such as Duchenne muscular dystrophy, and possibly even heart disorders in which other types of muscle become damaged.
- A role for cell sex in stem cell-mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency
- Muscle-derived stem cells
- NIH stem cell information
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.
- February 2014 guidelines for primary care providers outlining stroke risks unique to women
- Gender differences in quality of life after stroke and TIA: a cross-sectional survey of out-patients
- Preeclampsia and the risk of ischemic stroke among young women: results from the Stroke Prevention in Young Women Study
- Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study
- Medline Plus: Stroke
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.