research on stress hormones

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Article Contents

What is stress, what is the stress response, how does chronic stress affect your health, how do you know you’re stressed out, what should you do with this information, stress and your health.

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Bruce McEwen, Robert Sapolsky, Stress and Your Health, The Journal of Clinical Endocrinology & Metabolism , Volume 91, Issue 2, 1 February 2006, Page E2, https://doi.org/10.1210/jcem.91.2.9994

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Generally speaking, stress means pressure or strain. Life constantly subjects us to pressures. In people, stress can be physical (e.g., disease), emotional (e.g., grief), or psychological (e.g., fear).

Individuals vary in their ability to cope with stress. How you see a situation and your general physical health are the two major factors that determine how you will respond to a stressful event or to repeated stress.

Genes and things that happen to you early in life (e.g., child abuse or neglect), even in the womb, can affect how you handle stressful situations, possibly making you more likely to over-react. Overeating, smoking, drinking, and not exercising, which can often result from being under stress, can also add to the negative effects of stress.

Allostasis is the process of how the body responds to stress, whether it is acute (short-term) or chronic (long-term).

The best-known acute stress response is the “fight or flight” reaction that happens when you feel threatened. In this case, the stress response causes the body to release several stress hormones (e.g., cortisol and adrenaline) into the bloodstream. These hormones intensify your concentration, ability to react, and strength. Also, your heart rate and blood pressure increase, and your immune system and memory are shaper. After you have dealt with the short-term stress, your body returns to normal.

Chronic or long-term stress, however, poses a problem. If you repeatedly face challenges and your body is constantly producing higher levels of hormones, it doesn’t have time to recover. Stress hormones build up in the blood and, over time, can cause serious health problems.

Digestive system. Stomach ache is common due to a slow down in the emptying of the stomach; also diarrhea due to more activity in the colon.

Obesity. Increase in appetite, which can lead to weigh gain. (Being overweight or obese puts you at risk for diabetes and cardiovascular disease.)

Immune system. Weakening of the immune system so that you are more likely to have colds and other infections.

Nervous system. Anxiety, depression, loss of sleep and lack of interest in physical activity. Memory and decision-making can also be affected.

Cardiovascular system. Increase in blood pressure, heart rate, and blood fats (cholesterol and triglycerides). Also, increase in blood sugar (glucose) levels (especially in evening hours) and appetite (which contributes to weight gain). A(ll of these effects are risk factors for heart disease, atherosclerosis and stroke, as well as obesity and diabetes.)

Fatigue, depression

Chest pain or pressure, rapid heartbeat

Dizziness, shakiness, difficulty breathing

Menstrual cycle irregularities, erectile dysfunction (impotence), loss of libido (sex drive)

These symptoms may also lead to loss of appetite, overeating and poor sleep, all of which can have serious consequences for your health.

Usually these symptoms are minor and may be relieved through coping skills such as learning to relax, removing yourself for a time from the things that stress you out, and exercising. If the symptoms are severe, however, you may need to seek medical help to be able to identify the source of your stress and the best way to manage it.

There are practical steps you can take to cut back on stress. Regular, moderate exercise improves thought process and mood. So are relaxing, getting a good night’s sleep, and seeking emotional support from family and friends. You can also reduce the long-term effects of chronic stress by eating a healthy, low-fat diet and avoiding smoking and excessive drinking. However, if your symptoms continue or worsen, you should see your doctor.

Find-an-Endocrinologist (physician referral): www.hormone.org or call 1-800-HORMONE

Introduction to the Endocrine System, Hormones and Glands: www.hormone.org

Medline Plus (NIH): http://www.nlm.nih.gov/medlineplus/stress.html

U.S. Dept. of Health and Human Services: http://www.4woman.gov/faq/stress.htm

For more information on how to find an endocrinologist, download free publications, translate this fact sheet into other languages, or make a contribution to The Hormone Foundation, visit www.hormone.org/bilingual or call 1-800-HORMONE. The Hormone Foundation, the public education affiliate of The Endocrine Society ( www.endo-society.org ), serves as a resource for the public by promoting the prevention, treatment, and cure of hormone-related conditions. This page may be reproduced non-commercially by health care professionals and health educators to share with patients and students. Translation by MEDI-FLAG Corp.

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Stress hormones: physiological stress and regulation of metabolism

Affiliation.

• 1 WISDEM, University Hospital Coventry and Warwickshire, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK. [email protected]
• PMID: 19758844
• DOI: 10.1016/j.coph.2009.08.007

Stress, defined as a state of threatened homeostasis, mobilizes a complex spectrum of adaptive physiologic and behavioral responses that aim to re-establish the challenged body homeostasis. The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) constitute the main effector pathways of the stress system, mediating its adaptive functions. In western societies, indices of stress correlate with increasing rates of both obesity and metabolic syndrome which have reached epidemic proportions. Recent data indicate that chronic stress, associated with mild hypercortisolemia and prolonged SNS activation, favors accumulation of visceral fat and contributes to the clinical presentation of visceral obesity, type 2 diabetes, and related cardiometabolic complications. Reciprocally, obesity promotes a systemic low-grade inflammation state, mediated by increased adipokine secretion, which can chronically stimulate the stress system.

Publication types

• Adaptation, Physiological / physiology*
• Depression / complications
• Depression / metabolism
• Diabetes Mellitus, Type 2 / complications
• Diabetes Mellitus, Type 2 / metabolism
• Energy Metabolism / physiology*
• Hormones / metabolism*
• Hypothalamo-Hypophyseal System / metabolism*
• Inflammation / complications
• Inflammation / metabolism
• Metabolic Syndrome / complications
• Models, Biological
• Obesity / complications
• Obesity / metabolism
• Pituitary-Adrenal System / metabolism*
• Stress, Physiological*
• Sympathetic Nervous System / metabolism
• Sympathetic Nervous System / physiology

Appointments at Mayo Clinic

• Stress management
• Chronic stress puts your health at risk

Chronic stress can wreak havoc on your mind and body. Take steps to control your stress.

Your body is made to react to stress in ways meant to protect you against threats from predators and other aggressors. Such threats are rare today. But that doesn't mean that life is free of stress.

Instead, you likely face many demands each day. For example, you may take on a huge workload, pay bills or take care of your family. Your body treats these everyday tasks as threats. Because of this, you may feel as if you're always under attack. But you can fight back. You don't have to let stress control your life.

Understanding the natural stress response

When you face a perceived threat, a tiny region at the brain's base, called the hypothalamus, sets off an alarm system in the body. An example of a perceived threat is a large dog barking at you during your morning walk. Through nerve and hormonal signals, this system prompts the adrenal glands, found atop the kidneys, to release a surge of hormones, such as adrenaline and cortisol.

Adrenaline makes the heart beat faster, causes blood pressure to go up and gives you more energy. Cortisol, the primary stress hormone, increases sugar, also called glucose, in the bloodstream, enhances the brain's use of glucose and increases the availability of substances in the body that repair tissues.

Cortisol also slows functions that would be nonessential or harmful in a fight-or-flight situation. It changes immune system responses and suppresses the digestive system, the reproductive system and growth processes. This complex natural alarm system also communicates with the brain regions that control mood, motivation and fear.

When the natural stress response goes wild

The body's stress response system is usually self-limiting. Once a perceived threat has passed, hormones return to typical levels. As adrenaline and cortisol levels drop, your heart rate and blood pressure return to typical levels. Other systems go back to their regular activities.

But when stressors are always present and you always feel under attack, that fight-or-flight reaction stays turned on.

The long-term activation of the stress response system and too much exposure to cortisol and other stress hormones can disrupt almost all the body's processes. This puts you at higher risk of many health problems, including:

• Depression.
• Digestive problems.
• Muscle tension and pain.
• Heart disease, heart attack, high blood pressure and stroke.
• Sleep problems.
• Weight gain.
• Problems with memory and focus.

That's why it's so important to learn healthy ways to cope with your life stressors.

Why you react to life stressors the way you do

Your reaction to a potentially stressful event is different from everyone else's. How you react to your life stressors is affected by such factors as:

• Genetics. The genes that control the stress response keep most people at a fairly steady emotional level, only sometimes priming the body for fight or flight. More active or less active stress responses may stem from slight differences in these genes.
• Life experiences. Strong stress reactions sometimes can be traced to traumatic events. People who were neglected or abused as children tend to be especially at risk of experiencing high stress. The same is true of airplane crash survivors, people in the military, police officers and firefighters, and people who have experienced violent crime.

You may have some friends who seem relaxed about almost everything. And you may have other friends who react strongly to the slightest stress. Most people react to life stressors somewhere between those extremes.

Learning to react to stress in a healthy way

Stressful events are facts of life. And you may not be able to change your current situation. But you can take steps to manage the impact these events have on you.

You can learn to identify what causes you stress. And you can learn how to take care of yourself physically and emotionally in the face of stressful situations.

Try these stress management tips:

• Eat a healthy diet and get regular exercise. Get plenty of sleep too.
• Do relaxation exercises such as yoga, deep breathing, massage or meditation.
• Keep a journal. Write about your thoughts or what you're grateful for in your life.
• Take time for hobbies, such as reading or listening to music. Or watch your favorite show or movie.
• Foster healthy friendships and talk with friends and family.
• Have a sense of humor. Find ways to include humor and laughter in your life, such as watching funny movies or looking at joke websites.
• Volunteer in your community.
• Organize and focus on what you need to get done at home and work and remove tasks that aren't needed.
• Seek professional counseling. A counselor can help you learn specific coping skills to manage stress.

Stay away from unhealthy ways of managing your stress, such as using alcohol, tobacco, drugs or excess food. If you're worried that your use of these products has gone up or changed due to stress, talk to your health care provider.

There are many rewards for learning to manage stress. For example, you can have peace of mind, fewer stressors and less anxiety, a better quality of life, improvement in conditions such as high blood pressure, better self-control and focus, and better relationships. And it might even lead to a longer, healthier life.

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• How stress affects your health. American Psychological Association. https://www.apa.org/topics/stress/health. Accessed March 19, 2021.
• Stress effects on the body. American Psychological Association. https://www.apa.org/topics/stress/body. Accessed March 19, 2021.
• Lower stress: How does stress affect the body? American Heart Association. https://www.heart.org/en/healthy-living/healthy-lifestyle/stress-management/lower-stress-how-does-stress-affect-the-body. Accessed March 18, 2021.
• Stress and your health. U.S. Department of Health & Human Services. https://www.womenshealth.gov/mental-health/good-mental-health/stress-and-your-health. Accessed March 18, 2021.
• AskMayoExpert. Stress management and resiliency (adult). Mayo Clinic. 2019.
• Seaward BL. Essentials of Managing Stress. 5th ed. Jones & Bartlett Learning; 2021.
• Seaward BL. Managing Stress: Skills for Self-Care, Personal Resiliency and Work-Life Balance in a Rapidly Changing World. 10th ed. Jones & Bartlett Learning; 2022.
• Olpin M, et al. Stress Management for Life. 5th ed. Cengage Learning; 2020.
• Hall-Flavin DK (expert opinion). Mayo Clinic. March 23, 2021.

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Music and Health: What You Need To Know

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Yes, according to a growing body of research. Listening to or making music affects the brain in ways that may help promote health and manage disease symptoms.

Performing or listening to music activates a variety of structures in the brain that are involved in thinking, sensation, movement, and emotion. These brain effects may have physical and psychological benefits. For example, music causes the release of brain chemicals (neurotransmitters and hormones) that can evoke emotional reactions, memories, and feelings and promote social bonds. Music can even affect the structure of the brain. Certain structures in the brain have been found to be larger in musicians than nonmusicians, with particularly noticeable changes in people who started their musical training at an early age.

Increasing evidence suggests that music-based interventions may be helpful for health conditions that occur during childhood, adulthood, or aging. However, because much of the research on music-based interventions is preliminary, few definite conclusions about their effects have been reached. Many reports on the potential benefits of music-based interventions come from observations of individuals or small groups of people. Evidence of this type is valuable for suggesting new ideas, but carefully designed, scientifically rigorous studies of larger numbers of people are needed to provide stronger evidence on whether music-based interventions are effective for specific purposes.

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Music therapy is a health profession in which music is used within a therapeutic relationship to address physical, emotional, cognitive, and social needs. The term “music therapy” is not a description of a specific type of intervention. Instead, it indicates the education, training, and credentials of the therapist who is delivering the intervention.

Music therapy may involve a variety of different activities, including music improvisation, music listening, song writing, music performance, and learning through music. Music therapists may work in many different settings, such as hospitals, outpatient clinics, nursing homes, senior centers, rehabilitation facilities, or schools.

Some of the music-based interventions described in this fact sheet fit the definition of music therapy, but others do not. For example, music-based interventions that involve listening to recorded music are often delivered by health professionals other than music therapists (such as nurses), and therefore do not fit the definition of music therapy.

You can learn more about music therapy on the website of the American Music Therapy Association .

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In general, research studies of music-based interventions do not show any negative effects. However, listening to music at too high a volume can contribute to noise-induced hearing loss. You can find out about this type of hearing loss on the National Institute on Deafness and Other Communication Disorders website .

In addition, because music can be associated with strong memories or emotional reactions, some people may be distressed by exposure to specific pieces or types of music. Extensive playing of musical instruments can lead to pain and injury. Music-based interventions that involve exercise or other types of movement could also lead to injury if appropriate safety precautions are not taken.

.header_greentext{color:green!important;font-size:24px!important;font-weight:500!important;}.header_bluetext{color:blue!important;font-size:18px!important;font-weight:500!important;}.header_redtext{color:red!important;font-size:28px!important;font-weight:500!important;}.header_darkred{color:#803d2f!important;font-size:28px!important;font-weight:500!important;}.header_purpletext{color:purple!important;font-size:31px!important;font-weight:500!important;}.header_yellowtext{color:yellow!important;font-size:20px!important;font-weight:500!important;}.header_blacktext{color:black!important;font-size:22px!important;font-weight:500!important;}.header_whitetext{color:white!important;font-size:22px!important;font-weight:500!important;}.header_darkred{color:#803d2f!important;}.Green_Header{color:green!important;font-size:24px!important;font-weight:500!important;}.Blue_Header{color:blue!important;font-size:18px!important;font-weight:500!important;}.Red_Header{color:red!important;font-size:28px!important;font-weight:500!important;}.Purple_Header{color:purple!important;font-size:31px!important;font-weight:500!important;}.Yellow_Header{color:yellow!important;font-size:20px!important;font-weight:500!important;}.Black_Header{color:black!important;font-size:22px!important;font-weight:500!important;}.White_Header{color:white!important;font-size:22px!important;font-weight:500!important;} What does research show about music-based interventions for people with health conditions?

The preliminary research that has been done so far suggests that music-based interventions may be helpful for anxiety, depressive symptoms, and pain associated with a variety of health conditions, as well as for some other symptoms associated with dementia, multiple sclerosis, Parkinson’s disease, and other conditions. 

.header_greentext{color:green!important;font-size:24px!important;font-weight:500!important;}.header_bluetext{color:blue!important;font-size:18px!important;font-weight:500!important;}.header_redtext{color:red!important;font-size:28px!important;font-weight:500!important;}.header_darkred{color:#803d2f!important;font-size:28px!important;font-weight:500!important;}.header_purpletext{color:purple!important;font-size:31px!important;font-weight:500!important;}.header_yellowtext{color:yellow!important;font-size:20px!important;font-weight:500!important;}.header_blacktext{color:black!important;font-size:22px!important;font-weight:500!important;}.header_whitetext{color:white!important;font-size:22px!important;font-weight:500!important;}.header_darkred{color:#803d2f!important;}.Green_Header{color:green!important;font-size:24px!important;font-weight:500!important;}.Blue_Header{color:blue!important;font-size:18px!important;font-weight:500!important;}.Red_Header{color:red!important;font-size:28px!important;font-weight:500!important;}.Purple_Header{color:purple!important;font-size:31px!important;font-weight:500!important;}.Yellow_Header{color:yellow!important;font-size:20px!important;font-weight:500!important;}.Black_Header{color:black!important;font-size:22px!important;font-weight:500!important;}.White_Header{color:white!important;font-size:22px!important;font-weight:500!important;} Pain

As mentioned in other sections of this fact sheet, there’s evidence that music-based interventions may help to relieve pain associated with specific health conditions. The two review articles listed below describe evidence indicating that music may be helpful for pain more generally. Newer research continues to find evidence that music may be helpful for pain from a variety of causes, but not every study has shown a beneficial effect. 

• A 2016 review looked at 97 studies (9,184 participants) of music-based interventions for acute or chronic pain associated with a variety of health problems and medical procedures. The overall evidence suggested that music-based interventions may have beneficial effects on both pain intensity and emotional distress from pain and may lead to decreased use of pain-relieving medicines.
• A 2017 review of 14 randomized trials (1,178 participants) of music-based interventions for various types of chronic pain found that the interventions reduced self-reported chronic pain and associated depressive symptoms, with a greater effect when the music was chosen by the participant rather than the researcher. The study participants had a variety of conditions that can cause chronic pain, including cancer, fibromyalgia, multiple sclerosis, or osteoarthritis, and most of the interventions involved listening to recorded music.
• Many but not all newer studies of music-based interventions for pain have had promising results. For example, in recent studies, music-based interventions were helpful for pain associated with childbirth, cancer chemotherapy, a procedure in which shock waves are used to break up kidney stones, retrieval of eggs for in vitro fertilization, treatment of nose fractures, and sickle cell disease. However, music didn’t seem to be helpful for reducing moderate pain further after use of a lidocaine spray for loop electrosurgical excision (a gynecological procedure), and the results of studies on pain during cystoscopy (a procedure in which a tube is inserted into the bladder) and pain during colonoscopy were inconsistent.

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Music-based interventions have been evaluated for their effects on anxiety in a variety of disease conditions and health care settings. Some examples are given in this section, and others are discussed in the sections on specific health conditions. Most studies have had promising results, except for studies on anxiety associated with dental care.

• A 2013 review of 26 studies (2,051 participants) showed that listening to recorded music significantly reduced anxiety in people who were waiting to have surgery. However, there was potential for bias in most of the studies because the investigators who performed the studies knew which participants had listened to music.
• A 2016 review of 17 studies (1,381 participants) that evaluated the effect of music-based interventions on anxiety in adults with cancer suggested that the interventions may have a large anxiety-reducing effect. However, there was a high risk of bias in the studies. 
• A 2015 review of 5 studies (290 participants) in people who were having dialysis treatments suggested that listening to music reduced anxiety. However, these studies have limitations because of their small size and high risk of bias.
• A 2018 review concluded that it’s unclear whether listening to music is helpful for dental anxiety. Some studies have suggested that listening to music as a distraction may not be adequate to reduce anxiety in children or highly anxious adults who are having dental care. More active types of music-based interventions (for example, a music-assisted relaxation technique that’s taught to the patient in advance) might be helpful in dental settings but have not been evaluated in formal studies.  

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It’s uncertain whether music-based interventions are helpful for people with ASD.

• A 2021 review of 22 studies (850 participants) on music therapy for children with ASD was unable to reach any definite conclusions on whether adding music therapy to their care is beneficial, although some studies had promising results. For example, some studies of educational music therapy (involving techniques such as musical games) showed possible benefits on the children’s speech, and some studies of improvisational music therapy (in which children produce music) showed possible benefits on social functioning.
• One particularly notable study of music therapy for children with ASD (which was included in the review described above) was a multinational trial involving 364 children from 9 countries. It is the largest study completed so far, and its design was especially rigorous. In this study, the severity of symptoms related to difficulties in social communication did not differ between children who received music therapy along with standard care and those who received standard care alone.

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Preliminary evidence suggests that music-based interventions may be helpful for several types of distress in people with cancer.

• A 2021 review of randomized controlled trials (studies in which participants were randomly assigned to a music-based intervention group or a control group), which included 81 trials and 5,576 participants, concluded that in adults with cancer, music interventions may have a large anxiety-reducing effect, a moderately strong beneficial effect on depression, a moderate pain-reducing effect, and a large effect on the quality of life. Most of the trials had a high risk of bias, so their results need to be interpreted with caution. Only seven of the studies included in this review involved children. Two of these studies suggested a beneficial effect on anxiety; no other conclusions could be reached from the small amount of evidence available.
• A 2021 review of 11 studies (491 participants) on music interventions for children and adolescents with cancer, which included some studies that were less rigorous than a randomized controlled trial, found evidence suggesting that music-based interventions may decrease anxiety, perceived pain, and depression symptoms and improve state of mind, self-esteem, and quality of life.

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A 2021 systematic review of 12 studies (812 participants) showed that music-based interventions were helpful for shortness of breath, anxiety, and sleep quality in adults with COPD but were not helpful for depression. Because the studies were brief (several days to 12 months) and because researchers measured effects in different ways in different studies, there is some uncertainty about the conclusions.

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Much research is being done on the potential benefits of music-based interventions for people with cognitive impairment or various types of dementia, such as Alzheimer’s disease. Limited evidence suggests that music-based interventions may improve emotional well-being, behavioral challenges, and quality of life in people with these conditions. Whether the interventions have benefits for cognitive functioning is unclear; effects might depend on the population studied or the type of intervention used.

• A 2018 review evaluated 22 studies (1,097 participants) of music-based interventions for people with dementia who were living in institutions. Some of the interventions were receptive (listening to music), some were active (singing, playing instruments, moving to music, etc.), and some were a combination of the two. The evidence from these studies indicated that music-based interventions probably reduce depressive symptoms and improve overall behavioral challenges. They may also improve emotional well-being and quality of life and reduce anxiety. However, the interventions may have little or no effect on agitation, aggression, or cognitive function.
• A 2021 review looked at 21 studies (1,472 participants) of people with either mild cognitive impairment or mild or moderate dementia; some of the people studied were living in institutions, but others were living in the community. All the music interventions were active; studies that only involved listening to music were not included. Nine of the studies (495 participants) were included in a quantitative analysis of effects on cognitive functioning; this analysis indicated that the music-based interventions had a small beneficial effect. There was also some evidence for beneficial effects on mood and quality of life.

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A 2017 review looked at 9 studies (421 participants) of music-based interventions in adults or adolescents with depression. There was moderate-quality evidence that adding music-based interventions to usual treatment improved depression symptoms when compared with usual treatment alone. Music-based interventions also helped decrease anxiety levels and improve functioning of people with depression (for example, their ability to maintain involvement in work, activities, and relationships).

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A 2020 systematic review of 7 studies (334 participants) found evidence that music-based interventions were beneficial for pain, depression, and quality of life in people with fibromyalgia. However, the amount of research was limited, and the quality of the research was low.

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A 2021 review of music-based interventions for people with multiple sclerosis (10 trials, 429 participants) found consistent evidence that the interventions were beneficial for coordination, balance, some aspects of gait and walking, emotional status, and pain, but no effect was observed for mental fatigability or memory.

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Researchers are evaluating the potential benefits of several types of music-based interventions for Parkinson’s disease symptoms. 

• Rhythmic auditory stimulation.  Rhythmic auditory stimulation uses pulsed sounds (such as those produced by a metronome) to help people synchronize their movements to the rhythm of the sounds. This technique is used to help people with Parkinson’s disease improve their ability to walk. A 2021 analysis of 5 studies (209 total participants) showed significant improvements in gait speed and stride length in people with Parkinson’s disease who participated in rhythmic auditory stimulation. However, the quality of evidence was low, and the number of studies and participants was small.
• Music-based movement therapy.  Music-based movement therapy combines physical activities such as dance or rhythmic exercises with music. Therapies that involve physical activity have been shown to be helpful for a variety of Parkinson’s disease symptoms. Adding music to the therapy might have additional benefits by providing auditory cues for movement and making the activities more enjoyable. A 2021 analysis of 17 studies (598 participants) of music-based movement therapy showed evidence of improvements in motor function, balance, freezing of gait, walking speed, and mental health but not gait cadence, stride length, or quality of life.
• Singing. The potential benefits of singing for people with Parkinson’s disease have been studied primarily in terms of effects on speech. In a 2016 review of 7 studies (102 participants), 5 studies found some evidence of a beneficial effect on speech.

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Music-based interventions are widely used in neonatal intensive care units. However, evidence for physiological benefits for newborn infants is limited. 

• In a 2020 review of 16 studies (826 infants), 12 of the studies found some evidence of benefits on physiological outcomes (such as heart rate or oxygen saturation), but several of the studies included only small numbers of infants, and the intervention methods used varied from one study to another. The reviewers concluded that the current data are insufficient to confirm physiological benefits. No harmful effects of music-based interventions were seen in the studies included in this review.

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Music-based interventions have been evaluated as adjunct treatments (additions to usual treatment) for people with schizophrenia. A 2020 review of 18 studies (1,212 participants) indicated that adjunct music-based interventions may improve a group of schizophrenia symptoms known as “negative symptoms,” such as reduced emotion and self-neglect, as well as depression symptoms and quality of life. However, music-based interventions did not reduce “positive symptoms,” such as hallucinations and delusions. The quality of the evidence was low.

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Listening to music may improve sleep quality in people with insomnia.

• A 2022 review looked at 13 studies (1,007 participants) that examined the effect of listening to recorded music in people with insomnia. The studies suggested music had no effect on insomnia severity compared to no treatment or treatment as usual. Moderate-certainty evidence did suggest, however, that listening to music has a beneficial effect on subjective sleep quality. The studies also provided low-certainty evidence that listening to music might help improve the speed of falling asleep, the length of time spent sleeping, and the amount of time a person is asleep compared to the total time spent in bed.
• It’s common for older people to have trouble sleeping. A 2021 review looked at 16 studies of music-based interventions for sleep in older adults (812 participants); 11 studies evaluated music listening, and the other 5 evaluated more complex interventions. The results were mixed, with some studies suggesting that the music interventions were helpful, while others did not.

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Music-based interventions, particularly music therapy, may be helpful for improving physical and psychological markers associated with stress, according to two related reviews.

• In a 2020 review with 104 studies (9,617 participants), investigators looked at the effects of a variety of music-based interventions on measures associated with stress, including both physical measures (heart rate, blood pressure, and levels of stress-related hormones) and psychological measures (anxiety, nervousness, restlessness, and feelings of worry). The music-based interventions had a small-to-medium sized beneficial effect on the physical measures and a medium-to-large beneficial effect on the psychological measures. 
• A second review looked at 47 studies (2,747 participants) of music therapy (excluding other music-based interventions) and found an overall medium-to-large beneficial effect on stress-related outcomes. The effects were greater than those seen in the larger review. The investigators who performed the review suggested that the opportunity for music therapists to tailor interventions to the needs of individual patients might account for the difference.

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Music-based interventions may be helpful in the rehabilitation of people who have had a stroke. A 2019 review of 27 studies (730 participants) found positive effects on physical status (upper-limb activity, various aspects of walking, balance), cognition (paying attention, communication), and mood. In particular, rhythmic auditory stimulation (which involves the use of a metronome combined with physical activities) had beneficial effects on gait and balance, and receptive music therapy (which involves listening to music while performing another task) was helpful for mood and some aspects of cognitive function.

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Tinnitus is the symptom that people often describe as “ringing in the ears,” although it can also sound like roaring, clicking, hissing, or buzzing. It can be caused by noise-induced hearing loss, blockage of the ear canal by earwax, ear or sinus infections, or other health conditions, or by starting or stopping various medications. Sometimes, tinnitus has no obvious cause.

• Sound therapies. Various types of sounds, including music, have been used to try to mask tinnitus. However, according to a 2019 review of studies conducted up to that time, the effects of these sound therapies are modest; few people achieve complete remission of tinnitus from sound therapies.
• Notched music therapy. A specific type of music therapy called “notched” music therapy has been suggested as a possible way to reduce the severity of tinnitus. Notched music therapy involves listening to music that has been modified to remove sounds close in frequency to the frequency of the tinnitus sound perceived by the patient. Two recent studies that compared notched music with conventional music did not find notched music to be more helpful in reducing the symptoms or impact of tinnitus. However, some earlier studies suggested that the loudness of tinnitus sounds could be reduced with notched music therapy.

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NIH and the John F. Kennedy Center for the Performing Arts, in association with the National Endowment for the Arts, are sponsoring an initiative called Sound Health to increase understanding of music’s effect on the brain and the potential clinical applications. The first Sound Health research projects began in 2019. Some projects are investigating music’s mechanism of action in the brain and how music may be applied to treat symptoms of disorders such as Parkinson’s disease, stroke, and chronic pain. Others are looking at the effects of music on children’s developing brains.

Topics of NCCIH-supported studies within the Sound Health initiative include:

• The effects of music-based interventions on neurodevelopment and pain response in preterm infants
• Using self-generated rhythmic cues to enhance gait in people with Parkinson’s disease
• The impact of singing interventions on markers of cardiovascular health in older people with cardiovascular disease

In collaboration with the Foundation for the NIH and the Renée Fleming Foundation, NIH has developed a toolkit for rigorous, reproducible, well-powered music-based interventions for brain disorders of aging, such as Alzheimer’s disease, Parkinson’s disease, and stroke. Three workshops were held in 2021 to gather input from experts in a variety of relevant fields, and a request for information was issued to get stakeholder feedback. The toolkit , which was released in 2023, will be pilot tested in demonstration projects. NCCIH is playing a lead role in this effort.

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Nccih clearinghouse.

The NCCIH Clearinghouse provides information on NCCIH and complementary and integrative health approaches, including publications and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.

Toll-free in the U.S.: 1-888-644-6226

Telecommunications relay service (TRS): 7-1-1

Website: https://www.nccih.nih.gov

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Know the Science

NCCIH and the National Institutes of Health (NIH) provide tools to help you understand the basics and terminology of scientific research so you can make well-informed decisions about your health. Know the Science features a variety of materials, including interactive modules, quizzes, and videos, as well as links to informative content from Federal resources designed to help consumers make sense of health information.

Explaining How Research Works (NIH)

Know the Science: How To Make Sense of a Scientific Journal Article

Understanding Clinical Studies (NIH)

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• Aalbers   S, Fusar-Poli L, Freeman RE, et al.  Music therapy for depression . Cochrane Database of Systematic Reviews. 2017;(11):CD004517. Accessed at cochranelibrary.com on October 29, 2021.
• Bieleninik Ł, Geretsegger M, Mössler K, et al.  Effects of improvisational music therapy vs enhanced standard care on symptom severity among children with autism spectrum disorder. The TIME—a randomized clinical trial . JAMA. 2017;318(6):525-535.
• Bradt J, Dileo C, Magill L, et al. Music interventions for improving psychological and physical outcomes in cancer patients . Cochrane Database of Systematic Reviews. 2016;(8):CD006911. Accessed at cochranelibrary.com on October 29, 2021.
• Bradt J, Dileo C, Shim M. Music interventions for preoperative anxiety . Cochrane Database of Systematic Reviews. 2013;(6):CD006908. Accessed at cochranelibrary.com  on October 29, 2021.
• Burrai F, Apuzzo L, Zanotti R. Effectiveness of rhythmic auditory stimulation on gait in Parkinson disease: a systematic review and meta-analysis . Holistic Nursing Practice. June 11, 2021. [Epub ahead of print].
• Cheever T, Taylor A, Finkelstein R, et al. NIH/Kennedy Center workshop on music and the brain: finding harmony . Neuron. 2018;97(6):1214-1218.
• Collins FS, Fleming R. Sound health: an NIH-Kennedy Center initiative to explore music and the mind . JAMA. 2017;317(24):2470-2471.
• de Witte   M, da Silva Pinho A, Stams G-J, et al. Music therapy for stress reduction: a systematic review and meta-analysis . Health Psychology Review. 2022;16(1):134-159.
• de Witte   M, Spruit A, van Hooren S, et al. Effects of music interventions on stress-related outcomes: a systematic review and two meta-analyses . Health Psychology Review. 2020;14(2):294-324.
• Dorris   JL, Neely S, Terhorst L, et al. Effects of music participation for mild cognitive impairment and dementia: a systematic review and meta-analysis . Journal of the American Geriatrics Society.  2021;69(9):2659-2667.
• Foroushani SM, Herman CA, Wiseman CA, et al. Evaluating physiologic outcomes of music interventions in the neonatal intensive care unit: a systematic review . Journal of Perinatology. 2020;40(12):1770-1779.
• Garza-Villareal   EA, Pando V, Vuust P, et al. Music-induced analgesia in chronic pain conditions: a systematic review and meta-analysis . Pain Physician. 2017;20(7):597-610.
• Jespersen KV, Pando-Naude V, Koenig J, et al. Listening to music for insomnia in adults . Cochrane Database of Systematic Reviews. 2022;(8):CD010459. Accessed at cochranelibrary.com on September 8, 2022.
• Lee   JH. The effects of music on pain: a meta-analysis . Journal of Music Therapy. 2016;53(4):430-477.
• van der Steen   JT, Smaling HJ, van der Wouden JC, et al. Music-based therapeutic interventions for people with dementia . Cochrane Database of Systematic Reviews. 2018;(7):CD003447. Accessed at cochranelibrary.com on October 29, 2021.

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• Atipas   S, Therdphaothai J, Suvansit K, et al. A randomized, controlled trial of notched music therapy for tinnitus patients. Journal of International Advanced Otology. 2021;17(3):221-227.
• Barnish J, Atkinson RA, Barran SM, et al. Potential benefit of singing for people with Parkinson’s disease: a systematic review. Journal of Parkinson’s Disease. 2016;6(3):473-484.
• Bird HA. Overuse syndrome in musicians. Clinical Rheumatology. 2013;32(4):475-479.
• Bradt J, Teague A. Music interventions for dental anxiety. Oral Diseases. 2018;24(3):300-306.
• Brancatisano O, Baird A, Thompson WF. Why is music therapeutic for neurological disorders? The therapeutic music capacities model. Neuroscience and Biobehavioral Reviews. 2020;112:600-615.
• Buglione A, Saccone G, Mas M, et al. Effect of music on labor and delivery in nulliparous singleton pregnancies: a randomized clinical trial. Archives of Gynecology and Obstetrics.  2020;310(3):693-698.
• Burrai F, Magavern EF, Micheluzzi V, et al. Effectiveness of music to improve anxiety in hemodialysis patients. A systematic review and meta-analysis. Holistic Nursing Practice. 2020;34(6):324-333.
• Cakmak O, Cimen S, Tarhan H, et al. Listening to music during shock wave lithotripsy decreases anxiety, pain, and dissatisfaction. A randomized controlled study. Wiener Klinische Wochenscrift.  2017;129(19-20):687-691.
• Ç elebi D, Y ı lmaz E, Ş ahin ST, et al. The effect of music therapy during colonoscopy on pain, anxiety and patient comfort: a randomized controlled trial. Complementary Therapies in Clinical Practice. 2020;38:101084.
• Chantawong N, Charoenkwan K. Effects of music listening during loop electrosurgical excision procedure on pain and anxiety: a randomized trial. Journal of Lower Genital Tract Disease. 2017;21(4):307-310.
• Cheung CWC, Yee AWW, Chan PS, et al. The impact of music therapy on pain and stress reduction during oocyte retrieval—a randomized controlled trial. Reproductive Biomedicine Online. 2018;37(2):145-152.
• Çift   A, Benlioğlu C. Effect of different musical types on patient’s relaxation, anxiety and pain perception during shock wave lithotripsy: a randomized controlled study. Urology Journal. 2020;17(1):19-23.
• Gonz á lez-Mart í n-Moreno   M, Garrido-Ardila EM, Jim é nez-Palomares M, et al. Music-based interventions in paediatric and adolescents oncology patients: a systematic review. Children. 2021;8(2):73.
• Huang J, Yuan X, Zhang N, et al. Music therapy in adults with COPD. Respiratory Care. 2021;66(3):501-509.
• Jia   R, Liang D, Yu J, et al. The effectiveness of adjunct music therapy for patients with schizophrenia: a meta-analysis. Psychiatry Research. 2020;293:113464.
• Ko SY, Leung DYP, Wong EML. Effects of easy listening music intervention on satisfaction, anxiety, and pain in patients undergoing colonoscopy: a pilot randomized controlled trial. Clinical Interventions in Aging. 2019;14:977-986.
• Koelsch S. A neuroscientific perspective on music therapy. Annals of the New York Academy of Sciences. 2009;1169:374-384.
• Le Perf   G, Donguy A-L, Thebault G. Nuanced effects of music interventions on rehabilitation outcomes after stroke: a systematic review. Topics in Stroke Rehabilitation.  2019;26(6):473-484.
• Lopes   J, Keppers II. Music-based therapy in rehabilitation of people with multiple sclerosis: a systematic review of clinical trials. Arquivos de Neuro-psiquiatria.  2021;79(6):527-535.
• Mayer-Benarous   H, Benarous X, Vonthron F, et al. Music therapy for children with autistic spectrum disorder and/or other neurodevelopmental disorders: a systematic review. Frontiers in Psychiatry. 2021;12:643234.
• McClintock G, Wong E, Mancuso P, et al. Music during flexible cystoscopy for pain and anxiety – a patient-blinded randomized control trial. BJU International. 2021;128 Suppl 1:27-32. 
• Mumm J-N, Eismann L, Rodler S, et al. Listening to music during outpatient cystoscopy reduces pain and anxiety and increases satisfaction: results from a prospective randomized study. Urologia Internationalis . 2021;105(9-10):792-798. 
• Ortega   A, Gauna F, Munoz D, et al. Music therapy for pain and anxiety management in nasal bone fracture reduction: randomized controlled clinical trial. Otolaryngology—Head and Neck Surgery. 2019;161(4):613-619.
• Perković R, Dević K, Hrkać A, et al. Relationship between education of pregnant women and listening to classical music with the experience of pain in childbirth and the occurrence of psychological symptoms in puerperium. Psychiatria Danubina. 2021;33(Suppl 13):260-270.
• Petrovsky DV, Ramesh P, McPhillips MV, et al. Effects of music interventions on sleep in older adults: a systematic review. Geriatric Nursing.  2021;42(4):869-879.
• Pienkowski M. Rationale and efficacy of sound therapies for tinnitus and hyperacusis. Neuroscience. 2019;407:120-134.
• Piromchai   P, Chompunut S, Kasemsiri P, et al. A three-arm, single-blind, randomized controlled trial examining the effects of notched music therapy, conventional music therapy, and counseling on tinnitus. Otology & Neurotology. 2021;42(2):335-340.
• Robb SL, Hanson-Abromeit D, May L, et al. Reporting quality of music intervention research in healthcare: a systematic review. Complementary Therapies in Medicine. 2018;38:24-41.
• Rodgers-Melnick SN, Matthie N, Jenerette C, et al. The effects of a single electronic music improvisation session on the pain of adults with sickle cell disease: a mixed methods pilot study. Journal of Music Therapy.  2018;55(2):156-185.
• Silverman MJ, Gooding LF, Yinger O. It’s…complicated: a theoretical model of music-induced harm. Journal of Music Therapy. 2020;57(3):251-281.
• Speranza L, Pulcrano S, Perrone-Capano C, et al. Music affects functional brain connectivity and is effective in the treatment of neurological disorders. Reviews in the Neurosciences. March 24, 2022. [Epub ahead of print].
• Tang   H, Chen L, Wang Y, et al. The efficacy of music therapy to relieve pain, anxiety, and promote sleep quality, in patients with small cell lung cancer receiving platinum-based chemotherapy. Supportive Care in Cancer. 2021;29(12):7299-7306.
• Wang M, Yi G, Gao H, et al. Music-based interventions to improve fibromyalgia syndrome: a meta-analysis. Explore. 2020;16(6):357-362.
• Wolff AL, Ling DI, Casey EK, et al. Feasibility and impact of a musculoskeletal health for musicians (MHM) program for musician students: a randomized controlled pilot study. Journal of Hand Therapy. 2021:34(2):159-165.
• Zhou   Z, Zhou R, Wei W, et al. Effects of music-based movement therapy on motor function, balance, gait, mental health, and quality of life for patients with Parkinson’s disease: a systematic review and meta-analysis. Clinical Rehabilitation. 2021;35(7):937-951.

Acknowledgments

NCCIH thanks Wen Chen, Ph.D., Emmeline Edwards, Ph.D., and David Shurtleff, Ph.D., NCCIH, for their review of this fact sheet. 

This publication is not copyrighted and is in the public domain. Duplication is encouraged.

NCCIH has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your health care provider(s). We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy is not an endorsement by NCCIH.

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Hormones for menopause are safe, study finds. here's what changed.

Allison Aubrey

Low-dose estrogen can be taken orally, but it's also now available in patches, gels and creams. svetikd/Getty Images hide caption

Low-dose estrogen can be taken orally, but it's also now available in patches, gels and creams.

The benefits of hormone therapy for the treatment of menopause symptoms outweigh the risks. That's the conclusion of a new study published in the medical journal JAMA.

"Among women below the age of 60, we found hormone therapy has low risk of adverse events and [is] safe for treating bothersome hot flashes, night sweats and other menopausal symptoms, " says study author Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital. This is a departure from the advice many women have been given in the past.

The new analysis is based on two decades of follow-up data from the Women's Health Initiative study, which followed thousands of women taking hormone replacement therapy. The study was halted after it was found that women taking Prempro, which is a combination of estrogen and progestin, had higher risks of breast cancer and stroke.

A cheap drug may slow down aging. A study will determine if it works

"The findings were surprising," Manson says, pointing out that the reason the randomized trial was conducted was because scientists were trying to determine if hormone therapy decreased the risk of heart disease and other conditions.

After the initial findings came out, many women abruptly stopped the therapy. Prescriptions plummeted, and many healthcare providers still hesitate to recommend hormone therapy. But menopause experts say it's time to reconsider hormone therapy, because there's a lot known now that wasn't known two decades ago.

Most significantly, there are now different types of hormones — delivered at lower doses — that are shown to be safer.

"Women should know that hormone therapy is safe and beneficial," says Dr. Lauren Streicher , a clinical professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine.

Looking back, Dr. Streicher says, it's clear the Women's Health Initiative study was flawed and that some of the risks that were identified were linked to the type of hormones that women were given.

"We learned what not to do," Streicher says. The type of progestin used, known as medroxyprogesterone acetate , was "highly problematic," she says. This may have been linked to the increase in breast cancer seen among women in the earlier study. "So we don't prescribe that anymore," Streicher says.

Increasingly, other types of hormones are used, such as micronized progesterone which does not increase the risk of breast cancer, Streicher says. Micronized progesterone is a bioidentical hormone that has a molecular structure identical to the progesterone produced by women's ovaries, and tends to have fewer side effects.

Another problem with the study was the age of the women enrolled. Most of the women were over the age of 60, Streicher says. "And we know that there is a window of opportunity when it is the safest to start hormone therapy and that you get the most benefit." That window is typically between ages 50 and 60, she says.

Women who do strength training live longer. How much is enough?

Another risk identified in the Women's Health Initiative study, was an increased incidence of pulmonary embolism among women taking hormones. A pulmonary embolism is a blood clot that blocks blood flow to the lungs.

Since women in the study were taking estrogen orally, by pill, this may have increased their risk, Streicher says. A better option for people at risk of clots is to take estrogen through the skin, via a patch, a cream or gel.

"The advantage of a transdermal estrogen is that it is not metabolized by the liver," Streicher says. "And because it's not metabolized by the liver, we don't see that increase in blood clots."

With a range of hormone therapies available now, Dr Streicher says there's not a one-size fits all approach. "Hormone therapy is beneficial way beyond the benefits to just helping with hot flashes," she says. Ongoing research points to protection against bone loss and heart disease , too.

Streicher says women should talk to their healthcare providers about what options may best suit their needs.

Millions of women are 'under-muscled.' These foods help build strength

This story was edited by Jane Greenhalgh

• hot flashes
• hormone therapy
• hormone replacement therapy

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Hormones for menopause are safe, study finds. here's what changed.

The benefits of hormone therapy for the treatment of menopause symptoms outweigh the risks. That's the conclusion of a new study published in the medical journal JAMA.

"Among women below the age of 60, we found hormone therapy has low risk of adverse events and [is] safe for treating bothersome hot flashes, night sweats and other menopausal symptoms, " says study author Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital. This is a departure from the advice many women have been given in the past.

The new analysis is based on two decades of follow-up data from the Women's Health Initiative study, which followed thousands of women taking hormone replacement therapy. The study was halted after it was found that women taking Prempro, which is a combination of estrogen and progestin, had higher risks of breast cancer and stroke.

"The findings were surprising," Manson says, pointing out that the reason the randomized trial was conducted was because scientists were trying to determine if hormone therapy decreased the risk of heart disease and other conditions.

After the initial findings came out, many women abruptly stopped the therapy. Prescriptions plummeted, and many healthcare providers still hesitate to recommend hormone therapy. But menopause experts say it's time to reconsider hormone therapy, because there's a lot known now that wasn't known two decades ago.

Most significantly, there are now different types of hormones — delivered at lower doses — that are shown to be safer.

"Women should know that hormone therapy is safe and beneficial," says Dr. Lauren Streicher , a clinical professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine.

Looking back, Dr. Streicher says, it's clear the Women's Health Initiative study was flawed and that some of the risks that were identified were linked to the type of hormones that women were given.

"We learned what not to do," Streicher says. The type of progestin used, known as medroxyprogesterone acetate , was "highly problematic," she says. This may have been linked to the increase in breast cancer seen among women in the earlier study. "So we don't prescribe that anymore," Streicher says.

Increasingly, other types of hormones are used, such as micronized progesterone which does not increase the risk of breast cancer, Streicher says. Micronized progesterone is a bioidentical hormone that has a molecular structure identical to the progesterone produced by women's ovaries, and tends to have fewer side effects.

Another problem with the study was the age of the women enrolled. Most of the women were over the age of 60, Streicher says. "And we know that there is a window of opportunity when it is the safest to start hormone therapy and that you get the most benefit." That window is typically between ages 50 and 60, she says.

Another risk identified in the Women's Health Initiative study, was an increased incidence of pulmonary embolism among women taking hormones. A pulmonary embolism is a blood clot that blocks blood flow to the lungs.

Since women in the study were taking estrogen orally, by pill, this may have increased their risk, Streicher says. A better option for people at risk of clots is to take estrogen through the skin, via a patch, a cream or gel.

"The advantage of a transdermal estrogen is that it is not metabolized by the liver," Streicher says. "And because it's not metabolized by the liver, we don't see that increase in blood clots."

With a range of hormone therapies available now, Dr Streicher says there's not a one-size fits all approach. "Hormone therapy is beneficial way beyond the benefits to just helping with hot flashes," she says. Ongoing research points to protection against bone loss and heart disease , too.

Streicher says women should talk to their healthcare providers about what options may best suit their needs.

This story was edited by Jane Greenhalgh

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• Review Article
• Published: 05 May 2022

Plant hormone regulation of abiotic stress responses

• Rainer Waadt 1 , 2 ,
• Charles A. Seller 3 ,
• Po-Kai Hsu   ORCID: orcid.org/0000-0001-7265-7077 3 ,
• Yohei Takahashi 3 ,
• Shintaro Munemasa   ORCID: orcid.org/0000-0003-1204-1822 4 &
• Julian I. Schroeder   ORCID: orcid.org/0000-0002-3283-5972 3  

Nature Reviews Molecular Cell Biology volume  23 ,  pages 680–694 ( 2022 ) Cite this article

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• Plant hormones
• Plant signalling
• Plant stress responses

A Publisher Correction to this article was published on 30 May 2022

This article has been updated

Plant hormones are signalling compounds that regulate crucial aspects of growth, development and environmental stress responses. Abiotic stresses, such as drought, salinity, heat, cold and flooding, have profound effects on plant growth and survival. Adaptation and tolerance to such stresses require sophisticated sensing, signalling and stress response mechanisms. In this Review, we discuss recent advances in understanding how diverse plant hormones control abiotic stress responses in plants and highlight points of hormonal crosstalk during abiotic stress signalling. Control mechanisms and stress responses mediated by plant hormones including abscisic acid, auxin, brassinosteroids, cytokinins, ethylene and gibberellins are discussed. We discuss new insights into osmotic stress sensing and signalling mechanisms, hormonal control of gene regulation and plant development during stress, hormone-regulated submergence tolerance and stomatal movements. We further explore how innovative imaging approaches are providing insights into single-cell and tissue hormone dynamics. Understanding stress tolerance mechanisms opens new opportunities for agricultural applications.

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Change history, 30 may 2022.

A Correction to this paper has been published: https://doi.org/10.1038/s41580-022-00501-x

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Acknowledgements

The authors apologize to those authors whose research they have not cited due to limitations on the number of references. Research in the authors’ laboratories was supported by grants from the US National Institutes of Health to J.I.S. (GM060396-ES010337) and to C.A.S. (F32GM137544), the National Science Foundation to J.I.S. (MCB-1900567) and the Japan Society for the Promotion of Science to S.M. (18K05557 and 18KK0425).

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Rainer Waadt

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Cell and Developmental Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA

Charles A. Seller, Po-Kai Hsu, Yohei Takahashi & Julian I. Schroeder

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Environmental stresses that are associated with the non-living environment, such as weather conditions or the quality of the soil in which plants grow.

Plant-derived compounds that function as plant growth regulators either locally or over long distances and at low (submicromolar) concentrations.

A sudden change in the ambient solute concentration resulting in the water potential difference between cells and environments effects the tendency of water movement across cell membranes. Hypo-osmotic stress leads to water influx into cells, whereas hyper-osmotic stress leads to water efflux from cells.

Small pores in the leaf epidermis that are formed by guard cells to allow the uptake of CO 2 for photosynthesis in exchange for water loss.

Ion channels that respond to mechanical forces, for example, induced by membrane tension.

The removal of the 5′ methylguanosine cap, a key step in the regulated degradation of mRNAs.

A state in which seed germination is inhibited. ABA signalling promotes seed dormancy, while gibberellin signalling can repress it.

The directional growth of roots towards regions of the soil environment with higher water content.

The directional growth of roots away from regions of high salinity.

A vascular tissue that conveys water and nutrients from roots to stems and leaves.

A water-responsive root developmental programme active when water is asymmetrically available around the circumference of the root. Lateral roots preferentially form on the water-contacting side.

A water-responsive root developmental programme where the formation of lateral roots is repressed in regions of the soil environment that lack water.

A layer of cells that encircle the vascular tissue.

An adaptive response to prolonged drought stress where plants accelerate the transition to flowering in order to reproduce.

Varieties of rice ( Oryza sativa) that avoid submergence stress by activating stem and leaf elongation to rise above the water surface. This developmental programme depends on the hormones ethylene and gibberellin.

Changes in the cell membrane potential making it more positive.

Changes in the cell membrane potential making it more negative.

Indicators that allow the in vivo monitoring of hormone levels and downstream hormone signalling responses.

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Waadt, R., Seller, C.A., Hsu, PK. et al. Plant hormone regulation of abiotic stress responses. Nat Rev Mol Cell Biol 23 , 680–694 (2022). https://doi.org/10.1038/s41580-022-00479-6

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Research discovers plants utilize drought stress hormone to block snacking spider mites

by University of Cambridge

Recent findings that plants employ a drought-survival mechanism to also defend against nutrient-sucking pests could inform future crop breeding programs aimed at achieving better broadscale pest control.

Using an advanced fluorescent biosensor (ABACUS2) that can detect tiny changes in plant hormone concentrations at the cellular scale, scientists saw that abscisic acid (ABA), usually linked with drought response, started closing the plant's entry gates within 5 hours of being infested with spider mites .

Microscopic leaf pores (stomata) are important for gas exchange but are also the major sites for water loss . When there is a water shortage , plants act to conserve water by producing the drought stress hormone ABA to close their stomata.

Coincidentally, the closure of stomata also obstructs the preferred entry points for nutrient-sucking pests like spider mites. The two-spotted spider mite is one of the most economically damaging pests—it's not fussy and attacks a broad range of more than 1000 plants, including 150 crops.

Barely visible to the naked eye, these tiny pests pierce and then suck dry plant cells. They can build up to enormous numbers very quickly and can be one of the most destructive pests in the garden and horticulture industry, spoiling house plants and reducing yields of vegetables, fruit and salad crops.

There has been debate about ABA's role in pest resistance. Initially, it was noticed that stomata close when plants are attacked by nutrient-sucking pests, leading to various hypotheses, including that this closure could be a plant response to losing water due to the pests' feeding or even that the pests act to close stomata to prevent plants from sending distress volatiles to pest predators.

In a collaboration between the Centre for Plant Biotechnology and Genomics (CBGP) in Spain and Sainsbury Laboratory Cambridge University (SLCU), researchers studying how thale cress (Arabidopsis thaliana) responds to the two-spotted spider mite (Tetranychus urticae) have determined the plant leaps into action almost immediately, employing the same hormone as for drought to also block spider mites from penetrating plant tissues and, as a result, significantly reducing pest damage.

The findings published in Plant Physiology found the peak closure of stomata is achieved within a time frame of 24 to 30 hours.

"Open stomata are natural apertures where pests like aphids and mites insert their specialized feeding structures, called stylets, to pierce and then suck out the nutrient rich contents from individual sub-epidermal cells," said Irene Rosa-Díaz, who carried out the spider mite experiments at SLCU and CBGP during her Ph.D. with Professor Isabel Diaz at the Centro de Biotecnología y Genómica de Plantas, Universidad Polytécnica de Madrid, and National Institute of Agricultural and Food Research and Technology (UPM-INIA) .

"We were able to show mite infestation induced a rapid stomatal closure response, with the plant hormone ABA rising in the leaf tissues—highest in stomatal and vascular cells, but also all other leaf cells measured. We showed through multiple different experiments that stomatal closure hinders mites.

"Plants that were pre-treated with ABA to induce stomatal closure and then infested with mites showed decreased mite damage, while ABA-deficient mutant plants where stomata cannot close well and plants that have a more stomata are more susceptible to mites."

Alexander Jones' research group at SLCU develops in vivo biosensors that are revealing hormone dynamics in plants at unprecedented resolution, including ABACUS2 that quantified cellular ABA in these mite experiments.

Dr. Jones said the study highlights the important interactions between biotic and abiotic stresses in plants, "Early warning cues from mite feeding induces a cascade of immune signaling molecules, including jasmonic acid (JA) and salicylic acid (SA), among other chemical responses. Together, these results show that ABA accumulation and stomatal closure are also key defense mechanisms employed to reduce mite damage.

"The next step is to investigate what the initial mite-produced signal is that the plant is detecting that then results in ABA accumulation. The biochemical mechanisms being used by the plant as signals of pest attack could be anything, including mite feeding vibrations, mite salivary proteins, chemicals produced by the mites or mite activity, direct cell damage (wounds) or other molecules associated with the mites.

"Identifying the initial triggers could potentially be used to develop new crop treatments to arm the plants ahead of predicted pest infestations. Importantly, efforts to select for plants with altered stomatal traits, which already must balance a photosynthesis vs. water conservation trade-off, could also consider resistance to damaging pests."

Provided by University of Cambridge

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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Physiology, stress reaction.

Brianna Chu ; Komal Marwaha ; Terrence Sanvictores ; Derek Ayers .

Affiliations

Last Update: September 12, 2022 .

• Introduction

Any physical or psychological stimuli that disrupt homeostasis result in a stress response. The stimuli are called stressors and physiological and behavioral changes in response to exposure to stressors constitute the stress response. A stress response is mediated by a complex interplay of nervous, endocrine, and immune mechanisms that involves activation of the sympathetic-adreno-medullar (SAM) axis, the hypothalamus-pituitary-adrenal (HPA) axis, and immune system. [1]  The stress response is adaptive, to begin with, that prepares the body to handle the challenges presented by an internal or external environmental challenge (stressor) e.g., the body's physiologic responses to trauma and invasive surgery serve to attenuate further tissue damage. But if the exposure to a stressor is actually or perceived as intense, repetitive (repeated acute stress), or prolonged (chronic stress), the stress response becomes maladaptive and detrimental to physiology e.g., exposure to chronic stressors can cause maladaptive reactions including depression, anxiety, cognitive impairment, and heart disease. [2]  

• Cellular Level

The physiology of stress response has two components; a slow response, mediated by the HPA axis,  and a fast response, mediated by the SAM axis. The fast response due to activation of SAM results in increased secretion of norepinephrine(NE) and epinephrine(E) from the adrenal medulla into the circulation and increased secretion of NE from the sympathetic nerves and thus result in elevated levels of NE in the brain. The released E and NE interact with α- adrenergic and β-adrenergic receptors, present in the central nervous system and on the cell membrane of smooth muscles, and other organs throughout the body. The norepinephrine(NE) and epinephrine(E), once released, bind to specific membrane-bound G-protein receptors to initiate an intracellular cAMP signaling pathway that rapidly activates cellular responses. Activation of these receptors results in, contraction of smooth and cardiac muscles cells leading to vasoconstriction, increased blood pressure, heart rate, cardiac output, skeletal muscle blood flow,  increased sodium retention,  increased glucose levels (due to glycogenolysis and gluconeogenesis), lipolysis, increased oxygen consumption, and thermogenesis. It also leads to reduced intestinal motility, cutaneous vasoconstriction, bronchiolar dilatation. In addition, SAM activation cases behavioral activation (enhanced arousal, alertness, vigilance, cognition, focused attention, and analgesia).

The slow response is due to activation of the HPA axis resulting in the release of Corticotropin-releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus into the circulation. The CRH released from the hypothalamus acts on two receptors; CRH-R1 and CRH-R2.CRH-R1 is widely expressed in the brain in mammals. It is the key receptor for the stress-induced ACTH release from the anterior pituitary. CRH-R2 is expressed primarily in peripheral tissues including skeletal muscles, gastrointestinal tract, and heart, as well as in subcortical structures of the brain. Cortisol releasing hormone binding protein CRH-BP binds with CRH with a higher affinity than CRH to its receptors. CRH-BP gets expressed in the liver, pituitary gland, brain, and placenta. [3]  The role of CRH-BP as a controller of the bioavailability of CRH has support by studies finding 40 to 60% of CRH in the brain is bound by CRH-BP. [4]  In exposure to stress, the expression of CRH-BP increases in a time-dependent fashion, which is thought to be a negative feedback mechanism to decrease the interaction of CRH with CRH-R1. [2]  Serum cortisol level describes the body's total cortisol level, of which 80% is bound to cortisol binding globulin (CBG) and 10% is bound to albumin. Unbound cortisol is biologically active. 

The released CRH then stimulates the anterior pituitary gland to release adrenocorticotrophin hormone (ACTH) into the bloodstream. ACTH stimulates the adrenal cortex to secrete glucocorticoid hormones, such as cortisol, into the circulation. Cortisol's inactive form, cortisone, is catalyzed to its active form, cortisol, by 11 beta-hydroxysteroid dehydrogenases.

The HPA axis is regulated by pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP may play a role in the production of CRH and have a modulatory role in multiple levels of the HPA axis. [5]  Evidence also points to PACAP's involvement in the autonomic response to stress through increased secretion of catecholamines. [5]  The PACAP receptors are G-protein coupled and PACAP-R1 is the most abundant in both central and peripheral tissues. PACAP may also modulate estrogen's role in the potentiation of the acute stress response. [6]  

Once CRH is released, it binds with cortisol releasing hormone binding protein (CRH-BP) because CRH has a higher affinity for CRH-BP than for its receptors. CRH-BP gets expressed in the liver, pituitary gland, brain, and placenta. [5]  The role of CRH-BP as a controller of the bioavailability of CRH has support by studies finding 40 to 60% of CRH in the brain is bound by CRH-BP. [6]  

In exposure to stress, the expression of CRH-BP increases in a time-dependent fashion, which is thought to be a negative feedback mechanism to decrease the interaction of CRH with CRH-R1. [2]  Serum cortisol level describes the body's total cortisol level, of which 80% is bound to cortisol binding globulin (CBG) and 10% is bound to albumin. Unbound cortisol is biologically active. 

• Organ Systems Involved

Stress generally affects all systems of the body including cardiovascular, respiratory, endocrine, gastrointestinal, nervous, muscular, and reproductive systems. With regards to the cardiovascular system, acute stress causes an increase in heart rate, stronger heart muscle contractions, dilation of the heart, and redirection of blood to large muscles. The respiratory system works with the cardiovascular system to supply cells of the body with oxygen while removing carbon dioxide waste. Acute stress constricts the airway which leads to shortness of breath and rapid breathing. The endocrine system increases its production of steroid hormones, which include cortisol, to activate the stress response of the body. Stress can affect the gastrointestinal tract by affecting how quickly food moves through the bowels. It can also affect digestion and what nutrients the intestines absorb. With regards to the nervous system, stress will activate the sympathetic nervous system which in turn activates the adrenal glands. The parasympathetic nervous system facilitates the recovery of the body after the acute stress-induced crisis is over. Stress affects the musculoskeletal system by tensing up the muscles as a way of guarding against pain and injury. In the reproductive system, chronic stress can negatively impact sexual desire, sperm production/ maturation, pregnancy, and menstruation. 

The heightened autonomic response causes an increase in heart rate and blood pressure. During critical illness, catecholamine release decreases GI tract blood circulation. Plasma levels of norepinephrine and epinephrine during times of stress redistribute blood volume to conserve the brain's supply of blood. Stimulation of the sympathetic nervous system is varied but includes threats to the body such as hypoglycemia, hemorrhagic shock, exercise beyond the anaerobic threshold, and asphyxiation. [7]  Epinephrine is also associated with active escape, attack, and immobile fear.

A stressful situation, whether environmental or psychological, can activate a cascade of stress hormones that produce physiological changes. Activation of the sympathetic nervous system in this manner triggers an acute stress response called the "fight or flight" response. This enables a person to either fight the threat or flee the situation. The rush of adrenaline and noradrenaline secreted from the adrenal medulla causes almost all portions of the sympathetic system to discharge simultaneously as a widespread mass discharge effect throughout the entire body. Physiologic changes of this mass discharge effect include increased arterial pressure, more blood flow to active muscles and less blood flow to organs not needed for rapid motor activity, increased rate of blood coagulation, increased rates of cellular metabolism through the body, increased muscle strength, increased mental activity, increased blood glucose concentration, and increased glycolysis in the liver/muscle. The net effect of all these effects allows a person to perform more strenuous activity than normal. After the perceived threat disappears, the body returns to pre-arousal levels. 

Physical stress stimulates the HPA and sympathetic nervous system. Cortisol has various physiologic effects, including catecholamine release, suppression of insulin, mobilization of energy stores through gluconeogenesis and glycogenolysis, suppression of the immune-inflammatory response, and delayed wound healing. [8]  An effect of the downregulation of the immune response is the apoptosis of B-cells. [9] [10]  Wound healing is also delayed through effects on collagen synthesis. [11]  Aldosterone is a mineralocorticoid hormone that preserves blood pressure through sodium and water retention. 

Glucocorticoid binding receptors exist in the brain as mineralocorticoid and glucocorticoid receptors. The brain's first response to glucocorticoids is to preserve function. Glucocorticoid hormones such as cortisol, corticosterone, and dexamethasone have various effects of conserving energy and maintaining energy supply such as reduction of inflammation, restriction of growth, production of energy, removal of unnecessary or malfunctioning cellular components. [12]

• Related Testing

Various testing techniques are used to measure stress response in humans. The cortisol immunoassay can be used to study serum cortisone levels. Sympathetic responses are measurable through microneurography and norepinephrine levels. The microneurography technique involves the insertion of an electrode to a peripheral nerve to measure sympathetic activity in the skin and muscle of the upper or lower limbs. 

• Pathophysiology

Although restoration of homeostasis is the goal of the stress response, chronic stress leads to dysfunctional responses causing heart disease, stomach ulcers, sleep dysregulation, and psychiatric disorders. The HPA axis may become suppressed or dysregulated in these maladaptive responses to stress. Stress causes the cardiovascular system to respond with elevated blood pressure and heart rate, and chronic activation of this response is a major cause of cardiovascular disease. Coronary artery disease, stroke, and hypertension occur at a greater incidence in those with stress-related psychological disorders. The release of catecholamines in the stress response can have maladaptive effects in the gastrointestinal tract through decreased local blood flow. Chronic stress, weakens the immune system, increasing the probability of H pylori gastric ulcers and bleeding.  [13]   Sleep quality and quantity affect cortisol response to acute stress. Self-reported high sleep quality showed strong cortisol stress response, and fairly good sleep quality showed significantly weaker cortisol response in men but not in women. Independent of gender, a blunted cortisol response to stress was observed in people who reported trouble staying awake and difficulty maintaining enthusiasm. [14]  

Addison's disease, Cushing syndrome, and pheochromocytoma are diseases in the adrenal system, the latter of which play a role in the body's stress mechanisms via the release of cortisol and epinephrine. Patients have a lack of glucocorticoid and or mineralocorticoid hormones in Addison's disease.  [15] Hypercortisolism due to endogenous or exogenous causes is observed in Cushing syndrome.  [16]  Pheochromocytomas are catecholamine-secreting tumors of the adrenal glands.  [17]  

General adaptation syndrome also describes the different stress-induced physiological changes through three different stages, with the last two stages showing the pathological changes of extended stress. [18]  This syndrome is divided into the alarm reaction stage, resistance stage, and exhaustion stage. The alarm reaction stage refers to the initial symptoms of the body under acute stress and the "fight or flight" response. After the initial shock of the stressful event, the body begins to repair itself by lowering cortisol levels and normalizing the physiologic responses (i.e. blood pressure and heart rate). During this recovery phase, the body remains on alert until the stressful event is no longer an issue. However, if the stressful event persists for extended periods of time, the body will adapt to cope with the higher level of stress. The body will continue to secrete stress hormones which keep the body's physical response to stress elevated. This induces the resistance stage and includes symptoms of poor concentration, irritability, and frustration. If the stressful event continues to persist, the body will enter the exhaustion stage. Symptoms of this stage include burnout, fatigue, depression, anxiety, and reduced stress tolerance. As the stressful event persists, the body's immune system will continue to weaken. This is due to the suppressive effects of stress hormones on cells of the immune system.

• Clinical Significance

The body's physiologic responses to stress have significance in the clinical setting in many applications, including the management of healthy and hypo adrenal surgical patients and understanding how patients' lifestyle modifications may be related to the body's stress response. 

The physiologic stress of surgery causes cortisol levels to rise in a positive correlation to the severity of the surgery. In patients undergoing major surgeries as defined by the POSSUM scale, cortisol levels return to baseline on postoperative days 1-5. [8]  Postoperative pain severity was not found to correlate with cortisol levels after cardiac surgery. [7]  Postoperative opiate analgesia was not found to affect stress cortisol response to surgery in a study of cortisol levels during minor, moderate, and major surgeries. [8]  The varied level of cortisol secretion correlated to the stress of specific surgical operations has implications for hypo adrenal patients that require the replacement of cortisol when undergoing surgery.

Hydrocortisone injections for hypo adrenal patients undergoing surgery are given to replicate levels in patients undergoing surgery with normal adrenal function; this is thought to help hypo adrenal patients withstand the physiologic stress of surgery. Dose recommendations vary as well as a method of supplementation. [8] European guidelines suggest 100 mg of hydrocortisone intramuscularly before anesthesia regardless of surgery type. Endocrine Society recommendations suggest 100 mg of hydrocortisone intravenously followed by infusion that has as its basis the severity of the surgery. Testing cortisol level in surgeries of varying severity shows that peak cortisol correlates with surgical severity, but peak cortisol levels were demonstrated to be lower than previously suggested. [8]

ICU patients are subject to physical and environmental stress, and efforts have been made to investigate the link between cortisol levels and illness recovery, as well as to ameliorate stressors during the ICU stay that make it a problematic healing environment. Subjective patient perception of relaxation is heightened with the use of sleep adjuncts such as earplugs, eye masks, and relaxing music. However, these interventions did not influence nocturnal melatonin or cortisol level. [19]

Long-term exercise aids in the prevention of cardiovascular disease and adaption of baseline cardiac performance is thought to be one of the factors. Long-term moderate exercise is useful for relieving stress-induced cardiovascular response through changing baroreflex set points in the nucleus of the tractus solitarius for blood pressure control and blood volume homeostasis regulated by the paraventricular nucleus.

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Disclosure: Brianna Chu declares no relevant financial relationships with ineligible companies.

Disclosure: Komal Marwaha declares no relevant financial relationships with ineligible companies.

Disclosure: Terrence Sanvictores declares no relevant financial relationships with ineligible companies.

Disclosure: Derek Ayers declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Chu B, Marwaha K, Sanvictores T, et al. Physiology, Stress Reaction. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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