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Sleep, Pregnancy, And Your Future Health

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By Judette Louis MD, MPH University of South Florida, SWHR Interdisciplinary Network on Sleep Member and Mary Ashley Cain MD, University of South Florida

For many women, pregnancy can be a period of anxiety and concerns. After months of watching her diet and following the doctor’s orders, a new mother now must focus on her wonderful, rapidly growing and sometimes demanding, infant. As life moves on, mothers are happy to forget all the concerns of pregnancy, unaware that pregnancy provides a window into their future health.

One particular problem, poor sleep during pregnancy, is often blamed on heartburn, frequent urination, or even the baby’s movement. Poor sleep in pregnancy, however, may be due to the worsening of a condition known as sleep apnea. Women with sleep apnea experience pauses in breathing while they sleep which results in low oxygen levels in their blood. The brain registers these pauses and wakes the woman up to resume normal breathing. Symptoms of this condition can include snoring and excessive sleepiness during the day. Recent studies have confirmed that women with sleep apnea are two times as likely to develop pregnancy complications, such as gestational diabetes, gestational hypertension, or preeclampsia [1]. Having any of these conditions makes a woman’s pregnancy riskier, and the risk continues after pregnancy ends.

Studies increasingly suggest that women who have gestational diabetes, gestational hypertension, or preeclampsia are more likely to have heart disease later in life [2]. The studies have been so consistent that the American Heart Association now recognizes gestational diabetes, gestational hypertension, and preeclampsia as risk factors for heart disease in women [3]. Considering that heart disease is the number one cause of death in women, we need to pay attention to these studies.

One important question to ask is, “how soon do we see the difference?” The answer is concerning. One study found a 20 percent increase in heart disease and stroke among women who suffer from preeclampsia as early as three to five years after delivery [4]. This finding indicates that we may need to act quickly if we want to prevent heart disease.

The next important question is, “what can we do about it?” Doctors and researchers are looking for ways to prevent heart disease in women who experience these pregnancy complications. In the meantime, there are some well-recognized ways to lower your risk of heart disease. Women who breastfeed are 20 to 30 percent less likely to develop heart disease than women who have never breastfed. In addition, the American Heart Association also recommends “Life’s Simple 7” as key factors to achieving ideal heart health [5]. They include 2 ½ hours of moderate physical activity each week, controlling cholesterol, stopping smoking, eating healthier foods, maintaining a normal body weight, controlling blood pressure, and controlling blood sugar. Outside of pregnancy, treatment of sleep apnea has also been associated with a decrease in heart disease-related deaths in women [6]. If you have sleep apnea or have had pregnancy complications, talk to your healthcare provider about what you can do to decrease your chance of developing heart disease.

The Society for Women’s Health Research Interdisciplinary Network on Sleep is committed to promoting awareness of sex and gender differences in sleep and circadian rhythms across the lifespan, and the impact they have on health and wellbeing. Learn more about the Sleep Network here.

References

1. Facco FL, Parker CB, Reddy UM, et al. Association Between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus. Obstetrics & Gynecology. 2017;129(1):31-41.

2. Rich-Edwards JW, Fraser A, Lawlor DA, Catov JM. Pregnancy characteristics and women’s future cardiovascular health: an underused opportunity to improve women’s health? Epidemiologic reviews. 2014;36(1):57-70.

3. Mosca L, Benjamin E, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. Circulation. 2011;123(11):1-20.

4. Cain MA, Salemi JL, Tanner JP, Kirby RS, Salihu HM, Louis JM. Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes. American journal of obstetrics and gynecology. 2016;215(4):484 e481-484 e414.

5. Sacco RL. The new American Heart Association 2020 goal: achieving ideal cardiovascular health. Journal of Cardiovascular Medicine. 2011;12(4):255-257.

6. Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment cohort study. Annals of internal medicine. 2012;156(2):115-122.

Fruit flies 2

What Fruit Flies Can Tell Us About Human Sleep and Circadian Disorders

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By Amita Sehgal, PhD, University of Pennsylvania, SWHR Interdisciplinary Network on Sleep Member and Paula Haynes, PhD, University of Pennsylvania

Patients visit sleep clinics seeking both treatment and the solace of understanding that accompanies a clinical diagnosis: knowing that their sleep problems are not their fault, but are due to physiology and genetics. When people are unable to fall asleep or wake up at normal times, they may have a circadian rhythm disorder caused by a disruption in the body’s internal clock [1, 2]. Surprisingly, much of the basic biology of the body’s internal clock has been discovered by working on the tiny kitchen pest, the fruit fly. The fruit fly, known to researchers as Drosophila melanogaster, is oddly enough a perfect model for scientists to study the genetic basis of seemingly complex behaviors.

Some people may wake up spontaneously in the morning, but those who do not get quite enough sleep might be awoken at exactly the same time every day by an alarm, the voices of young children, or a hungry pet. In fact, people and most animals possess an internal time-keeping mechanism that tells us when it is time to wake up and when it is time to go to sleep, keeping us synchronized to the day/night cycle. This internal time-keeping mechanism is called our circadian clock, derived from the Latin ‘circa’ [about] ‘dian’ [a day], and, just like a wall clock, runs on a daily cycle of 24 hours.

Just like people, fruit flies also have an internal circadian clock. In the 1960’s, Ron Konopka, a student working with the famous Drosophila geneticist, Seymour Benzer began genetic studies of circadian rhythms in flies. Although Benzer was skeptical that specific genes would underlie daily behavioral rhythms, Konopka devised a way to identify mutant flies with disrupted circadian rhythms. Knowing that flies tend to emerge from their pupal cases at dawn, Konopka collected and bred the flies that emerged at inappropriate times. Konopka’s mutant flies were found to have a mutation in a single gene, which was named period [3,4].

Years later, other genes affecting circadian rhythms, such as timeless [5,6], Clock [7], cycle [8], Doubletime [9] and Jetlag [10], were discovered in flies, with many of these genes functioning similarly in mice and humans. Indeed, scientists also studied these genes in families that exhibit unusual sleep-timing patterns, such as one in which many members fall asleep between 6 to 8pm and wake up between 1 to 3am. Thanks to work on flies, scientists considered the period genes in humans as possible culprits and sure enough, traced the “earliness” to a mutation in the Period2 gene [11].

Following the successful use of fruit flies in understanding circadian rhythms, researchers now use flies to figure out what makes us sleepy [12,13]. Just as with circadian timing, the genes that drive sleep in fruit flies and humans are likely to be similar as well. In fact, caffeine keeps flies awake, just as it does people [14]. We have also discovered other genes, named sleepless [15] and redeye [16], which are needed to maintain sleep in flies, and others have found similar genes in mammals [17,18, 19]. Moving forward, scientists hope to use the humble fruit fly to uncover even greater mysteries, including understanding why we sleep at all.

The Society for Women’s Health Research Interdisciplinary Network on Sleep is committed to promoting awareness of sex and gender differences in sleep and circadian rhythms across the lifespan, and the impact they have on health and well-being. Learn more about the Sleep Network here.

References

  1. Sehgal, A. & Mignot, E. Genetics of sleep and sleep disorders. Cell 146, 194–207 (2011).
  2. Jones, C. R., Huang, A. L., Ptáček, L. J. & Fu, Y.-H. Genetic basis of human circadian rhythm disorders. Exp. Neurol. 243, 28–33 (2013).
  3. Bargiello, T. A., Jackson, F. R. & Young, M. W. Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 312, 752–754 (1984).
  4. Zehring, W. A. et al. P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 39, 369–76 (1984).
  5. Sehgal, A. et al. Rhythmic expression of timeless: a basis for promoting circadian cycles in period gene autoregulation. Science 270, 808–10 (1995).
  6. Sehgal, A., Price, J. L., Man, B. & Young, M. W. Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science 263, 1603–6 (1994).
  7. Allada, R., White, N. E., So, W. V, Hall, J. C. & Rosbash, M. A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell 93, 791–804 (1998).
  8. Rutila, J. E. et al. CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless. Cell 93, 805–14 (1998).
  9. Kloss, B. et al. The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon. Cell 94, 97–107 (1998).
  10. Koh, K., Zheng, X. & Sehgal, A. JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS. Science 312, 1809–12 (2006).
  11. Toh, K. L. et al. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291, 1040–3 (2001).
  12. Shaw, P. J., Cirelli, C., Greenspan, R. J. & Tononi, G. Correlates of sleep and waking in Drosophila melanogaster. Science 287, 1834–7 (2000).
  13. Hendricks, J. C. et al. Rest in Drosophila is a sleep-like state. Neuron 25, 129–38 (2000).
  14. Nall, A. H. et al. Caffeine promotes wakefulness via dopamine signaling in Drosophila. Sci. Rep. 6, 20938 (2016).
  15. Koh, K. et al. Identification of SLEEPLESS, a sleep-promoting factor. Science 321, 372–6 (2008).
  16. Shi, M., Yue, Z., Kuryatov, A., Lindstrom, J. M. & Sehgal, A. Identification of Redeye, a new sleep-regulating protein whose expression is modulated by sleep amount. Elife 3, e01473 (2014).
  17. Ni, K.-M. et al. Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep. Elife 5, 745–752 (2016).
  18. Puddifoot, C. A., Wu, M., Sung, R.-J. & Joiner, W. J. Ly6h Regulates Trafficking of Alpha7 Nicotinic Acetylcholine Receptors and Nicotine-Induced Potentiation of Glutamatergic Signaling. J. Neurosci. 35, (2015).
  19. Wu, M., Puddifoot, C. A., Taylor, P. & Joiner, W. J. Mechanisms of inhibition and potentiation of α4β2 nicotinic acetylcholine receptors by members of the Ly6 protein family. J. Biol. Chem. 290, 24509–18 (2015).
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SWHR Convenes Leaders in Health Policy for Second Annual Awards Dinner Symposium: The State of Women’s Health

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The Society for Women’s Health Research (SWHR®) held its Second Annual Awards Dinner Symposium: The State of Women’s Health in Washington, DC, on March 22, 2017, gathering some of the best minds in health policy to discuss advancements in women’s health, and to explore existing policy challenges in understanding gender and ethnic disparities in health.

Amy M. Miller, PhD, president and CEO of SWHR, delivered the welcoming remarks, followed by Monica P. Mallampalli, PhD, MSc, Vice President of Scientific Affairs at SWHR, who spoke about the tremendous progress in women’s health and then introduced the event speakers.

Cynthia Hess, PhD, Associate Director of Research Institute for Women’s Policy Research (IWPR) shared findings on women’s health and well-being across the U.S. based on state level data published in IWPR’s Status of Women in the States 2015 report.

“Good policy needs to be based on data acknowledging that women’s experiences are different from men, and that experiences among women and men vary according to practice such as race and ethnicity, age, sexual identity, geographic location, and so forth,” said Dr. Hess.

Marsha Henderson, MCRP, Assistant Commissioner for Women’s Health at the U.S. Food and Drug Administration (FDA), discussed the Office of Women’s Health at FDA’s improvements to the quality of life for women and their families, particularly through ensuring inclusion of women in clinical trials, publicizing pregnancy registries, as well as advising about FDA’s wide range of regulated products including foods, pharmaceuticals, and medical devices.

Linda Blount, MPH, President and CEO of Black Women’s Health Imperative (BWHI), spoke about how big data in health research can often overlook underlying social determinants. She shared findings from BWHI’s IndexUS, the first comparative index of black women’s health.

Andrew Sperling, JD, Director of Federal Legislative Advocacy at the National Alliance on Mental Illness, addressed gender differences in mental illness and the need for more precise diagnostics of many psychiatric and neurodevelopmental disorders.

While the status of women’s health in the U.S. has improved, disparities and health outcomes for women of different racial, ethnic, and socioeconomic groups still need to be addressed through increased investments in prevention and treatments. SWHR will work with these organizations to address these challenges and facilitate the necessary advances to improve the health and well-being of all women.

The symposium concluded with a brief Q&A session, followed by a networking reception that led into SWHR’s 27th Annual Awards Dinner.

SWHR expresses gratitude to all who supported and attended the event, including our generous sponsors Amgen, Eli Lilly and Company, Spectrum Communications, and Valeant Pharmaceuticals.

menopausal-woman

Menopausal Hot Flashes: Middle of the Night Sleep Intruders

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By Fiona C. Baker, PhD, SRI International, SWHR Interdisciplinary Network on Sleep Member

It was 2 am when SJ woke up feeling hot, clammy, and bothered. She threw off the blanket in hopes of cooling down. Unfortunately, this experience was nothing new for her. She knew it was going to take a while to get back to sleep.

While approaching and passing menopause, around 80 percent of women experience transient periods of flushing, sweating, and a sensation of heat known as hot flashes. When they occur during the night, they can also be called night sweats [1]. While an occasional flash lasting a couple of minutes may not sound like much of a problem, some women experience this many times throughout the day and even at night. A woman whose sleep is interrupted will soon notice additional interferences with her daily life. This impact will be reflected in her daytime functioning, mood, and health.

A laboratory study of 34 perimenopausal women by Dr. Baker’s lab at SRI International found that around 70 percent of nighttime hot flashes woke women up, disrupting their sleep (objectively measured with sensors that detect brain activity) [2]. Women were most attuned to wakeful periods that co-occurred with hot flashes during the night.

Hot flashes can be the cause of chronic sleep disruption and can perpetuate insomnia, keeping women awake by feeling like they are losing control over their sleep, worrying about the impact of hot flashes on their sleep quality, and consequently how well they will function the next day. Hot flashes can persist for several years past menopause and are therefore a potential long-term source of sleep disruption, which in turn, affects quality of life, including mental and physical health. Therefore, hot flashes are a priority symptom that women should discuss with their healthcare provider.

Treatments can be tailored to the needs of each woman, taking into account the severity of the hot flashes, whether or not they disrupt both daytime functioning and sleep, where they are in the menopausal transition (pre-, peri-, post-, or surgical menopause), and whether they may have any other medical conditions that could add to any sleep disruption, such as sleep apnea. Treatment options include hormone therapy, non-hormonal pharmacological treatments such as selective serotonin reuptake inhibitors and gabapentin, or non-pharmacological choices specifically targeting sleep disruption such as cognitive behavioral therapy for insomnia [3, 4]. Cognitive behavioral therapy along with a healthy lifestyle can help women cope with their menopausal symptoms and put them back in control of their sleep. So if hot flashes are disrupting your day-to-day activities and/or your nighttime sleep, ask questions and talk to your healthcare provider.

The Society for Women’s Health Research Interdisciplinary Network on Sleep is committed to promoting awareness of sex and gender differences of sleep and circadian rhythms across the lifespan, and the impact they have on health and wellbeing. Learn more about the Sleep Network here.

References:

  1. Melby, M.K., et al., Methods used in cross-cultural comparisons of vasomotor symptoms and their determinants. Maturitas, 2011. 70(2): p. 110-119.
  2. de Zambotti, M., et al., Magnitude of the impact of hot flashes on sleep in perimenopausal women. Fertil Steril, 2014. 102(6): p. 1708-15.e1.
  3. Baker, F.C., et al., Insomnia in women approaching menopause: Beyond perception. Psychoneuroendocrinology, 2015. 60: p. 96-104.
  4. Joffe, H., A. Massler, and K.M. Sharkey. Evaluation and management of sleep disturbance during the menopause transition. Seminars in reproductive medicine, 2010. 28: p. 404-421.

 

Woman_Man-staring-at-sky-webfriendly

Women and Alzheimer’s Disease: The Facts Behind the Headlines

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By Michelle M. Mielke, PhD, Mayo Clinic, SWHR Interdisciplinary Network on Alzheimer’s Disease Member

In the last few years, several reports have placed women at the forefront of Alzheimer’s disease (AD). These reports have generated misleading headlines stating that women are at greater risk of developing AD compared to men. However, the numbers behind these headlines are not clear. There has also been little discussion about risk factors for AD that may be more important for women than men. Below is some clarity on what the phrase “women are at greater risk” means and some AD risk factors that have been found to be stronger for women than men. Notably, women are more than twice as likely as men to provide care for affected family members [1]. Therefore, it is important to also understand AD risk factors that are stronger for men.

Are women at greater risk of developing AD?

The total number of women with AD is greater than the total number of men with AD [2]. The main reason for this is that age is the biggest risk factor for AD. Women live longer than men, therefore there are more women at older ages when the development of AD is most likely.

However, whether women are actually at greater ‘risk’ compared to men is not clear. For example, if you look at women and men of the same age, say 65 or even 85 years old, and compare their risk of developing AD over three years, virtually all studies from the U.S. suggest that women are not more likely to develop AD than men. The studies reporting that women are at greater risk of AD used data from European populations [3, 4].

Oftentimes, studies from the U.S. suggest that men may be at slightly greater risk up to the age of 75, women and men have the same risk from ages 75-84, and women at slightly greater risk after the age of 85. It is clear that these differences are not significantly different, therefore, headlines stating that women are at greater risk refer specifically to the total number of women with AD, which is partially explained by the fact that women live longer.

What risk factors are important?

While we cannot control our genes, there are modifiable risk factors for AD that we can address. Unfortunately, most studies of AD risk factors combine women and men, and do not attempt to identify risk factors that are more common or stronger among women versus men.

There is an ongoing push to highlight the need for this kind of research, and we are now beginning to identify some risk factors that vary in strength for men and women.

Education. Low socioeconomic status, education, and occupational attainment are risk factors for AD in both women and men. Due to women having historically less support to obtain higher education, the overall effect of this risk factor appears to be greater for women [3]. The increasing education levels and occupational attainments of women over the last few decades may be one explanation for why the incidence of dementia may be declining more for women [5, 6]. Education is not solely attained in the first two decades of life, therefore continuing one’s education through formal or informal classes during middle age and beyond retirement, can contribute to building up brain reserve. Social interactions can also be beneficial to brain health.

Cardiovascular risk factors. A diagnosis of hypertension, high cholesterol, and diabetes in mid-life has been associated with a greater risk of developing AD for both women and men, but the risk for women is greater than for men [e.g., 7]. Therefore, it is critical for women to make a conscious effort to prevent these risk factors through diet, exercise, weight management, and adequately treating them when they occur.

Hormonal therapies. Following data published by the Women’s Health Initiative study, which suggested that hormonal therapies were associated with an increased risk of dementia and cardiovascular disease in the mid-1990s, the frequency of hormonal therapies drastically decreased. However, an important caveat to this study was that women were randomized to the use of hormones an average of 10 years after menopause. It is now thought that initiation of hormones several years after menopause may increase the risk of adverse outcomes [8]. Recent randomized controlled trials of healthy women that start using hormones within 3 years of menopause have not found an increased risk of dementia or cognitive decline [9]. This research suggests that many women can safely use hormonal treatments for menopausal symptoms over short durations and that the treatments do not have adverse effects on memory or risk of AD. The ultimate decision to either start or stop these therapies should be based on a collaborative discussion between a woman and her healthcare provider.

Women who have had one or both ovaries removed prior to age 45 are also at an increased risk of developing AD. Research suggests that hormonal use up to the age of natural menopause (around 51 years of age), will reduce this increased risk [10].

Never married/widowed. Compared to women, men who have never married or are widowed, have a greater risk of developing AD [e.g., 11]. A potential reason for this consistent observation is that women are often the ones responsible for the healthcare of their family (e.g., getting kids and partners/husbands to doctors for regular check-ups, assuring everyone has a healthy diet, etc.), sometimes at the expense of their own health. Women also typically lead a couple’s engagement in social activities, which are beneficial for cognition. While these notions are a bit stereotypical and not true of all situations, they should not be ignored. Caregivers of older, single, or widowed men should be cognizant of this difference, and in turn help maintain regular check-ups and engagement in some type of social activity.

There is still more to be done in investigating new AD risk factors and discerning how established risk factors vary by gender. The Society for Women’s Health Research’s newly launched Interdisciplinary Network on Alzheimer’s Disease is committed to advocating for these goals in order to improve prevention, early detection, management, and care.

References

  1. Kasper JD, Freedman VA, Spillman BC. Disability and Care Needs of Older Americans by Dementia Status: An Analysis of the 2011 National Health and Aging Trends Study. U.S. Department of Health and Human Services. April 2014. Available at: https://aspe.hhs.gov/report/disability-and-care-needs-older-americans-dementia-status-analysis-2011-national-health-and-aging-trends-study. Accessed February 28, 2017.
  2. 2014 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 2014. 10(2): p. e47-92.
  3. Mielke MM, Vemuri P, Rocca WA. Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences. Clinical Epidemiology, 2014. 6: p. 37-48.
  4. Edland SD, Rocca WA, Petersen RC, et al., Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn. Archives of Neurology, 2002. 59(10): p. 1589-1593.
  5. Langa KM, Larson EB, Crimmins EM, et al., A comparison of the prevalence of dementia in the United States in 2000 and 2012. JAMA Internal Medicine, 2017. 177(1): p. 51-58.
  6. Matthews FE, Arthur A, Barnes LE, et al., A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet, 2013. 382(9902): p. 1405-1412.
  7. Pankratz VS, Roberts RO, Mielke MM, et al., Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging. Neurology, 2015. 84(14): p. 1433-1442.
  8. Brinton RD. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trends in Neurosciences, 2008. 31(10): p. 529-537.
  9. Gleason CE, Dowling NM, Wharton W, et al., Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Medicine, 2015. 12(6): p. e1001833.
  10. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity. Brain Research, 2011. 1379: p. 188-198.
  11. Miech RA, Breitner JC, Zandi PP, et al., Incidence of AD may decline in the early 90s for men, later for women: the Cache County study. Neurology, 2002. 58(2): p. 209-218.
pexels-photo-271897

Who Should Be Screened For Sleep Apnea? The Answer Is Not Always Obvious

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By Rebecca Nebel, PhD, Assistant Director of Scientific Programs at SWHR

There is insufficient current evidence to assess the benefits and harms of screening for obstructive sleep apnea in asymptomatic adults [1], according to an assessment recently released by the United States Preventative Services Task Force (USPSTF). USPSTF, an independent, volunteer panel of national experts in prevention and evidence-based medicine, makes recommendations about the effectiveness of specific preventive care services for patients. USPSTF’s finding also applies to individuals with sleep apnea who are not aware of their symptoms or do not report symptoms as a concern. This is troubling, as it may impede primary care providers from discussing the signs and symptoms of obstructive sleep apnea (which we will refer to as sleep apnea) with their patients.

Sleep apnea affects 34 percent of men and 17 percent of women [2]. It not only increases the risk for a number of cardiovascular and metabolic diseases (e.g. heart disease, stroke, and diabetes), but also for motor vehicle crashes and mortality [1].

Data shows that the delay between development of symptoms and a sleep apnea diagnosis can be upwards of 7 to 10 years [3, 4]. This delay occurs despite many visits to primary care providers [3]. Many individuals with sleep apnea do not report “textbook” symptoms of sleep apnea, which include excessive daytime sleepiness and snoring. For example, one study found that over one-third of patients with moderate or severe sleep apnea reported excessive daytime sleepiness [5, 6]. This suggests that many individuals with sleep apnea would not necessarily report “textbook” symptoms to their primary care providers. In light of USPSTF’s recent statement about screening for sleep apnea, it is unlikely that these individuals would be viewed as candidates for such an evaluation.

There is also a need to address sex and gender differences in sleep apnea symptoms. Sleep apnea is a widely under-recognized disorder, particularly in women. Studies estimate over 90 percent of women with sleep apnea are not diagnosed [7]. One reason for this under-diagnosis is that many women do not have “textbook” symptoms and are more likely to report non-“textbook” symptoms such as fatigue, insomnia, and mood disturbances [8, 9]. Healthcare providers may not recognize these signs of sleep apnea, which can lead to misdiagnosis and mistreatment. Consequently, it is important to raise awareness of the differences in sleep apnea symptoms between women and men. USPSTF does not address the explicit need for improving recognition (and ultimately prevention and treatment of sleep apnea) in women, despite evidence that women are at high risk for sleep apnea related health problems, such as cognitive impairment [10] and heart failure [11]. Healthcare providers may continue to miss proper diagnosis in women unless they take sex and gender differences in sleep apnea symptoms into account during primary care visits.

Pregnant women are explicitly excluded from USPSTF’s recommendation. Pregnancy is often a time where sleep apnea is unmasked or becomes exacerbated [12]. Sleep apnea during pregnancy increases the risk for adverse outcomes for both mother and baby, including preeclampsia, gestational diabetes, preterm birth, NICU admission, and maternal death [12, 13].

Because current screening tools may not be sensitive to measuring how sleep apnea presents itself in pregnant women and women in general, it is important that healthcare providers be vigilant towards non-“textbook” symptoms in women across their lifespan. It is crucial for primary care providers to ascertain a patient’s medical history, including sleep apnea symptoms, and to recognize that “textbook” symptoms as well as non-“textbook” symptoms (insomnia, fatigue, mood disturbances) all may be indicators of sleep apnea.

The Society for Women’s Health Research Interdisciplinary Network on Sleep is committed to promoting awareness of sex and gender differences of sleep and circadian rhythms across the lifespan, and the impact they have on health and well-being. Learn more about the Sleep Network here.

References

  1. US Preventive Services Task Force., Screening for obstructive sleep apnea in adults: US Preventive Services Task Force recommendation statement. JAMA, 2017.
  2. Peppard, P.E., et al., Increased prevalence of sleep-disordered breathing in adults. American journal of epidemiology, 2013. 177(9): p. 1006-1014.
  3. Rahaghi, F. and R.C. Basner, Delayed diagnosis of obstructive sleep apnea: don’t ask, don’t tell. Sleep and Breathing, 1999. 3(04): p. 119-124.
  4. Redline, S., et al., Patient Partnerships Transforming Sleep Medicine Research and Clinical Care: Perspectives from the Sleep Apnea Patient-Centered Outcomes Network. Journal of clinical sleep medicine, 2015. 12(7): p. 1053-1058.
  5. Carter, G.S., Screening for Improvement of Health Outcomes in Asymptomatic Obstructive Sleep Apnea. JAMA neurology, 2017.
  6. Young, T., et al., Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep, 2008. 31(8): p. 1071-1078.
  7. Young, T., et al., Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep, 1997. 20(9): p. 705-706.
  8. Kump, K., et al., Assessment of the validity and utility of a sleep-symptom questionnaire. American journal of respiratory and critical care medicine, 1994. 150(3): p. 735-741.
  9. Valipour, A., et al., Gender-related differences in symptoms of patients with suspected breathing disorders in sleep: a clinical population study using the sleep disorders questionnaire. Sleep, 2007. 30(3): p. 312.
  10. Yaffe, K., et al., Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA, 2011. 306(6): p. 613-9.
  11. Roca, G.Q., et al., Sex-Specific Association of Sleep Apnea Severity With Subclinical Myocardial Injury, Ventricular Hypertrophy, and Heart Failure Risk in a Community-Dwelling Cohort: The Atherosclerosis Risk in Communities-Sleep Heart Health Study. Circulation, 2015. 132(14): p. 1329-37.
  12. Louis, J.M., et al., Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009. Sleep, 2014. 37(5): p. 843.
  13. Louis, J., et al., Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women. Obstetrics and gynecology, 2012. 120(5).

 

tired woman

Chronic Fatigue Syndrome: Diagnostic Tests, Treatment, and Prevention Urgently Needed

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By Clarissa K. Wittenberg

This blog was inspired by the good news that the National Institutes of Health (NIH) has doubled its research budget for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, it was shocking to see that the increase was from $7.6 million last year to $15 million this year. This is a very small research budget given that hundreds of thousands, even as high as 2.5 million men, women, and children suffer from this syndrome. Several studies use different criteria for diagnosis making for a wide variance in prevalence. The economic cost of ME/CFS is estimated at $17 to $24 billion annually [1]. NIH is the nation’s premiere biomedical research agency and as such, whatever budget is allotted, its influence adds credibility to the importance of studying ME/CFS.

Comparison: Budgets for Multiple Sclerosis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

The NIH National Institute of Neurological Diseases and Stroke (NINDS) is the lead Institute for both ME/CFS and multiple sclerosis (MS). The 2017 budget for multiple sclerosis (MS) is $98 million, a decline from $115 million in 2016. The number of patients for MS and ME/CFS is similar and like ME/CFS, causation for MS has not been established, although there are accepted treatments for the disease. Both have serious symptoms and can cause severe disability. MS patients have benefited from research, medical treatment and emotional support, but ME/CFS patients continue to struggle. Both disorders need more generous budgets [2], however other disorders need increased funding as well. NIH current funding is at 2016 levels due to a Continuing Resolution and budgets for special projects such as the Cancer Moonshot, which are not yet accounted for. To date, the NIH budget has not kept pace with inflation [3].

NIH Confronts ME/CFS:

“Of the many mysterious human illnesses that science has yet to unravel, ME/CFS has proven to be one of the most challenging. I am hopeful that renewed focus will lead us toward the cause of this perplexing and debilitating disease so that new prevention and treatment strategies can be developed,” said Francis S. Collins. MD, PhD, Director of the NIH [4].

It is encouraging that NIH began an investigational clinical study of ME/CFS in October 2016, to determine new treatments and diagnostic tests in an effort to see if new technologies might aid in the understanding of the condition. Leading up to this effort is an NIH-sponsored Institute of Medicine report (now the National Academy of Medicine) [5], an NIH Pathways to Prevention meeting [6] as well an invigoration of the Trans-NIH ME/CFS Research Working Group. In 2015, NIH began an ME/CFS Special Interest Group to serve as a forum for finding the cause of ME/CFS and identifying clinically valuable treatments. 

What is ME/CFS?

What is this disorder? While the syndrome was long viewed cynically, ME/CFS is now acknowledged as a medical syndrome, not a psychiatric or psychological one [7]. It is not just a state of being tired or exhausted, it is a complicated disorder characterized by extreme fatigue, more intense than what is usually experienced after exhausting physical or mental work. The diagnosis demands the exclusion of other diseases with similar symptoms. ME/CFS fatigue is more comparable to the fatigue caused by radiation, head injuries, or other types of biological assault. Other symptoms are widespread muscle and joint pain, cognitive issues, and even headaches. The symptoms do not subside with rest and it is frequently noted that those who suffer from ME/CFS have higher rates of suicide.

Most people cannot overcome the fatigue through willpower, although there are stories of people with ME/CFS making extraordinary efforts on their best days to continue to carry out their life’s work. Laura Hillenbrand, author of Seabiscuit, and Unbroken: A World War II Story of Survival, Resilience, and Redemption, continued writing despite being homebound by her illness. Blake Edwards, the director of many movies including Pink Panther, worked for almost 15 years despite having ME/CFS. The majority cannot continue their normal lives and this disorder can last for months, years, or even a lifetime.

A Disease with 1,000 Names:

In 1860, the syndrome was identified and named “neurasthenia.” It was from that moment that the name changing began. Sometimes the syndrome was named after a preceding infection, such as “chronic Epstein-Barr syndrome,” “chronic mononucleosis syndrome,” or “atypical poliomyelitis.” It has been named after sites of outbreaks including “Iceland disease,” “Tapanui flu,” and “Lake Tahoe disease.” It has also been named after prominent patients such as Florence Nightingale and Charles Darwin. In 1993, the Centers for Disease Control and Prevention named it chronic fatigue syndrome. The Institute of Medicine report renamed it myalgic encephalomyelitis/chronic fatigue syndrome, however, since muscle pain (myalgic) and brain inflammation (encephlomylitis) are not the main symptoms, a change to systemic exertion intolerance disease or SEID is currently being considered.

The various names contain valuable clues about the nature of the syndrome. Each one in an effort to pin down its causation. Although the large variation in secondary symptoms probably played a role, the biggest mystery is why all these efforts have never connected. This suggests that new investigational and linkage studies such as the NIH clinical trial and the Open Medicine Foundation Big Data Study, conducted with severely ill ME/CFS patients, may offer new insights as they use novel technologies to interrelate genetics, immunology, neurology, sleep research, viral sequelae, and other domains together [8].

Doing Something About It:

Linda Tannenbaum is the CEO/President of the Open Medicine Foundation, which funds the study of ME/CFS and other chronic complex disorders. Tannenbaum learned about ME/CFS when her daughter was diagnosed with the condition. Similarly, Ron Davis, PhD and Professor of Biochemistry and Genetics at Stanford University School of Medicine and Director of the Board of the Open Medicine Foundation learned about the disease when his son was diagnosed with ME/CFS. These families know firsthand how lives are damaged by ME/CFS. The Foundation has begun its Big Data Study of Severe Cases of ME/CFS that will look into finding biomarkers and releasing that information to the scientific community. “Any one of us, regardless of age, can be fine one day and then struck with ME/CFS, and it can last a lifetime,” said Tannenbaum.

Patient Advocacy: A Relentless Force for Change

We live in an age of powerful patient advocacy, with patients now researching their own illnesses, writing blogs, shooting films, lobbying, and forming foundations in order to raise awareness about their conditions. In 2001, Kim Snyder, a highly honored filmmaker, released I Remember Me, as she was recovering from ME/CFS. Her film tells the stories of people with ME/CFS and is also available on YouTube. Unrest, a film by Jennifer Brea, premiered at the 2017 Sundance Festival. It depicts her life story beginning from a vibrant childhood to the sudden onset of ME/CFS while studying for her PhD. She has continued to be a highly visible advocate. Talking about her film, Brea ruefully remembers seeing I Remember Me when she was in high school and thinking, “change was just around the corner.”

These films convey the terrible disability, pain, and social crisis of ME/CFS in a way no written description could. Doctors are often taught via Grand Rounds where patients are presented so medical students can have a real sense of the disease. These films offer a similar opportunity for the public, as well as medical students and researchers.

Solving the Mystery

Improved communications can educate us all, as well as help patients to understand that they are not alone. Important questions such as the reason why the disease is more common in women, would advance the understanding and treatment of ME/CFS. Are men less likely to report this syndrome? Are there differences in treatment offered to women and men?

Clarissa K. Wittenberg was a science writer and senior communication officer at several NIH Institutes and Associate Director for Communications at the National Institute of Mental Health; a special assistant to the Director of the Office of Global Health, Office of the Secretary, HHS; and formerly a consultant for mental and overall health of underserved populations to the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center. She is Creative Director of the Washington Film Institute.

References:

  1. http://www.iom.edu/Reports/2015/ME-CFS.aspx
  2. The Tragic Neglect of Chronic Fatigue Syndrome, Olga Khazan, October 8, 2015, The Atlantic
  3. Inside (the Beltway) Scoop) Jennifer Zeitzer, February 3, 2017) http://faseb.org
  4. NIH takes action to bolster research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. NIH News Release, October 29, 2015
  5. Beyond Myalgic Encephalomyelitis/Chronic Fatigue: Redefining an illness, Institute of Medicine, Report Brief, February 2015
  6. Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, NIH Office of Disease Prevention, December 9-10, 2014
  7. Beyond ME/CFS Syndrome: redefining an illness https://www.ncbi.nlm.nih.gov/25695122
  8. Open Medicine Foundation (OMF), End ME/CFS Project Biomarker Discovery: Severely Ill Big Data Study
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Sexual and Gender Minorities: The Silent Majority in the World of Mental Health

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By Natalia Gurevich, SWHR Communications Intern

This past year mental health has been at the forefront of national coverage, especially with the recent presidential election, where both nominees acknowledged mental health as an issue of public health concern. For one group in particular, sexual and gender minorities, mental health is an issue compounded by additional stressors that can occur daily. Sexual and gender minorities are affected by more discrimination and stigma throughout their lives than the general population [1]. As a result, mental health issues also disproportionately affect this group [1].

Sexual and gender minorities are a group whose sexual identity, orientation, or practices differ from the majority of the population [2]. Sexual and gender minorities usually comprise of lesbian, gay, bisexual, and transgender (LGBT) individuals [2]. The term sexual and gender minority is fairly new, and is currently used by the National Institutes of Health, which established the Sexual & Gender Minority Research Office in September 2015. While many studies and groups still use LGBT or LGBTQ, for the purposes of inclusion and for this post, SWHR will use the term sexual and gender minority.

The population is probably slightly larger than reported, but those who publicly identify as a sexual and gender minority only make up about 3.4 percent of the U.S. population [3]. However, for this small minority group, suicide is one of the leading causes of death among those aged 10–24 years. Sexual and gender minority youth contemplate or attempt suicide 4 times more frequently than the general population [1].

Sexual and gender minorities are also more affected by disorders, like depression and substance abuse. Most of these disorders affect sexual and gender minority adolescents at a higher rate than their cis gender, heterosexual peers [4]. A lot of internalized disorders (mental health) and external disorders (drug and alcohol addiction) that begin to develop in teenage years often manifest themselves into deeper issues continuing into adulthood [5]. Therefore, many researchers focus on adolescence in sexual and gender minorities in an effort to better understand the root cause of mental health issues within this group.

A study published in 2008 by the Journal of Child Psychology and Psychiatry, found that stress was the main compounding factor [4] to higher rates of mental health issues in sexual and gender minorities compared to the rest of the population. Chronic stress leads to dysregulated emotions and sexual and gender minorities face multiple stressors during adolescence, including peer victimization, and in some cases, physical assault and rejection from their family [4]. Coping with these extraneous stressors, along with various other issues facing adolescents in general, potentially keep sexual minorities from developing emotional maturity and adaptability relative to their heterosexual peers [4], which can extend into adulthood.

Another study published in 2010 by the American Journal of Public Health found that three categories for discrimination—gender, race/ethnicity, and sexual orientation—were often compounded together, and when combined, led to higher rates of substance abuse [6], particularly in adulthood. An estimated 20-30 percent of sexual and gender minorities abuse substances, compared to about 9 percent of the general population [1].

Substance abuse is an external disorder that often goes hand-in-hand with internal disorders. Because sexual minorities face discrimination and social stigma on a higher basis than other subpopulations, daily stressors often increase their risk for anxiety, depression, panic attacks, suicidal ideation, psychological distress, body image disturbance, and eating disorders [2]. While the president-elect has spoken on mental health in the past, he has yet to announce a formal platform on the issue [7]. SWHR hopes that the new administration will recognize the current issues surrounding mental health and develop new policies to combat this public health concern.

Education and awareness on sexual and gender minorities and mental health should be addressed as early as possible in adolescents and continue into adulthood. If you are a member of the sexual and gender minority community or even if you are not, talk to your healthcare provider if you have any questions relating to mental health.

At SWHR, we believe that mental health is an important issue that affects members of every community, either personally or through a loved one. Everyone is entitled to receive the proper care and support they deserve, regardless of sexual orientation, gender, or race/ethnicity. Sexual and gender minorities belong to a group greatly affected by mental health issues, but are vastly underrepresented in research. All the mental health implications will remain relatively unknown without more research and education on this minority group. Learn more about SWHR and the work we do on mental health here.

References:

  1. https://www.nami.org/Find-Support/LGBTQ
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657897/
  3. http://www.gallup.com/poll/158066/special-report-adults-identify-lgbt.aspx
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881586/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976222/#B1
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937001/
  7. http://www.huffingtonpost.com/entry/this-election-vote-with-your-mind_us_580678f4e4b08ddf9ece1139

 

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One More Mom to Teenage Daughter Talk: The School Bathroom

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By Clare E. Close, MD, FAAP, SWHR Interdisciplinary Network on Urological Health in Women Member

It’s early morning and your teenage daughter runs out the door to school. Much will happen today that you may or may not hear about when you see her again tonight. It’s unlikely that you will hear anything about the school restrooms, yet during her day at school, your daughter is developing habits that can affect her bladder for her lifetime [1].

Three hours into the school day your daughter needs to urinate but doesn’t ask to leave her class because she can’t afford to miss information that will be on this week’s exam. Also this teacher gives extra credit to students who don’t ask for bathroom breaks. A minute later her urge to urinate is gone. During her short passing period to lunch she walks by the restroom, but is too busy texting her friend and doesn’t stop. She eats her lunch and heads to her next class. Suddenly she feels her bladder again. She heads to the bathroom but turns around because the floor looks dirty. Sitting down in class she crosses her legs and does not feel her bladder so much, which is good because her teacher does not allow bathroom breaks right after lunch.

Eight hours after leaving home, classes are over, and your daughter’s bladder feels so full that it hurts. She heads to the bathroom but the door is now locked to prevent afterschool vandalism. Arriving home she rushes into her bathroom but leaks on the way.

Scenarios like this may seem hyperbolic, but they are happening to teenagers every day. Because bladder health is rarely taught in middle or high school health studies, your daughter most likely has no idea that she should be taking better care of her bladder. Unless she has an obvious bladder problem such as infection, you also will probably never think about discussing your daughter’s bladder health.

We know children commonly hold their urine and stool in elementary school causing incontinence, bedwetting, and infection [2]. In middle school and high school there many more social, time, and academic pressures that keep adolescents from going to the bathroom [3]. Over time if your daughter holds her urine all day her bladder can become abnormal with a thick wall that can make her feel a sudden urge to go as well as make her leak urine. These problems can continue into your daughter’s adulthood [4]. To grow a healthy bladder your teenager should urinate every two to three hours and take time to relax and empty their bladder completely. Healthy eating and drinking plenty of water will help her have normal bowel movements, which are also important for a healthy bladder [5].

Talking to your daughter about her bathroom habits may seem uncomfortable because of her desire for independence and privacy, but it is important to connect with her about issues of bathroom access, cleanliness, and safety. The school nurse may be the best person to reach out to if your daughter tells you about such problems. Her life-long bladder health may depend on it.

The Society for Women’s Health Research (SWHR®) launched its Interdisciplinary Network on Urological Health in Women in 2015 to promote bladder and urinary tract health across a woman’s lifespan. To learn more about the network or about urological health, visit swhr.org.

References

  1. Fitzgerald MP, Thom DH, Wassel-Fyr C, et al: Childhood urinary symptoms predict adult overactive bladder symptoms. J Urol 2006; 175: 989
  2. Sureshkumar P, Craig, JC, Roy LP, et al. Daytime urinary incontinence in primary school children: a population-based survey. J Pediatr 2000;137:814
  3. Bauer RM and Huebner W. Gender differences in bladder control: from babies to elderly. World J Urol 2013; 31(5): 1081-5
  4. Franco I. Pediatric overactive bladder syndrome pathophysiology and management. Paediatr Drugs 2007; 9: 379
  5. Burgers R, Liem O, Canon S, et al: Effect of rectal distention on lower urinary tract function in children. J Urol 2010; 184:1680

 

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A Little Leakage Goes a Long Way

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By Natalia Gurevich, SWHR Communications Intern

There have been many times when we have hated our bladders. For making us get up to use the bathroom in the middle of the night, or making us stop every hour on the otherwise fun family road trip. However, many of us take our bladder health for granted. Our bladders work hard, and sometimes they aren’t quite as effective as we would hope.  The majority of women, pregnant or not, have at some point in their lives dealt with incontinence, the unintentional loss of urine [1]. Urinary incontinence occurs more often in women than in men because of a variety of contributing factors: pregnancy, vaginal delivery, and menopause. Weak bladder muscles, overactive bladder muscles, and nerve damage may also cause urinary incontinence in women [1]. Incontinence is typically a minor and rare nuisance easily solved. But for some women, incontinence can be a chronic issue that significantly impacts their quality of life, depending on the type of incontinence and the cause.

There are several types of urinary incontinence in women, including stress urinary incontinence where urine leaks after pressure is put on the bladder (ex. coughing, sneezing laughing), urge incontinence where there is an urgent feeling of needing to urinate, overflow incontinence where the bladder is never empty, and mixed incontinence which is having two or more types of incontinence [5]. The most common type of mixed incontinence is stress and urge incontinence together [2, 5].

Female athletes, both amateur and professional often suffer from stress urinary incontinence (SUI), with a few exceptions [2]. Over 41 percent of young female athletes reported at least one episode of stress urinary incontinence during high impact activities [2]. Because female athletes spend time gaining muscle one would think the pelvic muscles would get stronger as a result, but actually the overuse of the pelvic muscles causes them to become weak and fatigue more easily [9].  In addition, approximately 25 percent of women under age 40 experience SUI during physical activity [2].

In 2002, a study published in the International Urogynecology Journal took a sample of 291 elite athletes and dancers, who were on average 23 years old [3]. The study showed a high prevalence of leakage within gymnastics, at 56 percent of participants suffering from incontinence, closely followed by ballet at 43 percent, and aerobics at 40 percent. Other sports like badminton, volleyball, handball, and basketball also had a high occurrence of women with incontinence [3].

Incontinence and other related urinary conditions are often viewed as harmless, but the results can be embarrassing and a constant source of worry and discomfort for the women affected, even leading to social isolation, marital distress, depression. Urinary incontinence is stigmatizing for many women. Almost 90 percent of women with a urinary incontinence don’t discuss it with their healthcare providers [2] and therefore do not get the proper support and treatment they need. And yet, the condition is so common among women, with seven to 37 percent of women between the ages of 20-39 reporting some degree of incontinence [6].

There are numerous treatments available for each type of urinary incontinence including medication, devices, surgery, discipline therapy, or Kegel exercises or pelvic floor exercises, which for the majority of women can be effective.

If you are a woman, and especially if you are an athlete, contact your healthcare provider if you have questions or concerns about your urological health. SWHR’s Interdisciplinary Network on Urologic Health in Women helps to raise awareness of the impact of bladder health on women’s well-being across the lifespan [2]. The network aims to identify and close the gaps in knowledge, research, policy and education and disseminate information and provide support to the general public [2]. Learn more about incontinence from SWHR’s new Urology Network Report here.

References:

  1. http://www.medicinenet.com/urinary_incontinence_in_women/article.htm
  2. Liliana Losada et al., “Expert Panel Recommendations on Lower Urinary Tract Health of Women across their Lifespan.” Journal of Women’s Health. Epub ahead of print (2016).
  3. Thyssen et al., “Urinary incontinence in elite female athletes and dancers.” International Urogynecology Journal. 2002;13(1):15-7.
  4. Simeone et al., “Occurrence rates and predictors of lower urinary tract symptoms and incontinence in female athletes.”Urologia. 2010;77(2):139-46.
  5. https://www.womenshealth.gov/publications/our-publications/fact-sheet/urinary-incontinence.html
  6. “Urinary Incontinence in Women.” National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 2 Sept. 2010. <http://kidney.niddk.nih.gov/kudiseases/pubs/uiwomen/>
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327384/
  8. http://www.webmd.com/urinary-incontinence-oab/types-of-urinary-incontinence
  9. Jacome et al. “Prevalence and impact of urinary incontinence among female athletes.” International Journal of Gynecology & Obstetrics. 2011;114(1):60–63.
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