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Imaging The Effects Of Menopausal Hormone Therapy On The Brain

By | Blog Post, News

By Kejal Kantarci, MD, MS, Mayo Clinic-Rochester, Society for Women’s Health Research Interdisciplinary Network on Alzheimer’s Disease Member

Imaging provides a window into brain changes due to dementia decades before someone begins to show clinical symptoms of the disease. Volume of the brain gradually declines with advancing age, but this decline takes a faster course in people who experience more cognitive decline than is expected for their age and go on to develop dementia.

Brain volume measured with magnetic resonance imaging can distinguish people who are losing brain volumes faster than expected. Such accelerated loss of brain volume may lead to a decline in brain function and memory later in life[1]. Preserving brain volume during middle age, particularly in women as they transition into menopause, may protect against dementia and delay the occurrence of symptoms.

Another imaging technique, positron emission tomography, can detect brain plaques due to Alzheimer’s disease (AD). It is now known that these AD plaques occur more than a decade before a decline in memory performance is seen [2]. Clearing these plaques from the brain is an accepted strategy to prevent AD, and development of treatments for clearing these plaques from the brain are under way in individuals who are at an increased risk for AD due to their genetic make-up. Imaging with positron emission tomography is also being used to identify individuals who may benefit from such preventive treatments, and determine who responds to these treatments [3].

Hormone therapy has been shown to increase brain volume loss and the risk of dementia in women older than 65 years of age [4, 5]. However, hormone therapy used during the menopausal transition is thought to have protective effects on the brain [6]. More time and research is needed before we know whether hormone therapy regimens are preventing dementia in women. In the meantime, imaging techniques can be used to determine whether women using hormone therapies during the menopausal transition are receiving any brain benefits.

Menopausal hormone therapies come in different forms and doses. Some are administered as pills; others are administered topically or as a skin patch. Effects of the different forms of hormone therapies on the brain may also vary. Imaging studies performed in women who took menopausal hormone therapies early in menopause for four years showed that women who used the estrogen skin patch accumulated less AD plaques than women who used a different form of estrogen therapy or were not treated [7]. Furthermore, recent data indicate that the group of women who used the estrogen skin patch also preserved brain volume in a region that is responsible for decision-making [8]. It is possible that the potentially beneficial effects of the estrogen skin patch, which were revealed through imaging, may prevent decline in brain function and dementia in women as they age.

Imaging technology is now being used to determine early changes in the brain that may lead to a decline in brain function and dementia in the future. Detection of these early brain changes with imaging opens up the possibilities for early intervention and prevention of dementia. Future research will determine whether these brain changes detected through imaging will influence brain function later in life.

The Society for Women’s Health Research’s Interdisciplinary Network on Alzheimer’s Disease is committed to exploring, understanding, and leveraging the scientific basis of the roles of sex and gender in Alzheimer’s disease to inform prevention, providing guidance for research, clinical trials, and policy. Click here to learn more about SWHR’s work in Alzheimer’s disease. 


  1. Debette S, Seshadri S, Beiser A, et al. Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology. 2011; 77 (5): 461-468.
  2. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia. 2011; 7 (3): 280-292.
  3. Sperling RA, Jack Jr CR, Aisen PS. Testing the right target and right drug at the right stage. Science Translational Medicine. 2011; 3 (111): 111cm133.
  4. Resnick SM, Espeland MA, Jaramillo SA, et al. Postmenopausal hormone therapy and regional brain volumes: The WHIMS-MRI study. Neurology. 2009; 72 (2): 135-142.
  5. Shumaker SA, Reboussin BA, Espeland MA, et al. The Women’s Health Initiative Memory Study (WHIMS): A trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Controlled Clinical Trials. 1998; 19 (6): 604-621.
  6. Sherwin BB. Estrogen and memory in women: How can we reconcile the findings? Hormones and Behavior. 2005; 47 (3): 371-375.
  7. Kantarci K, Lowe VJ, Lesnick TG, et al. Early postmenopausal transdermal 17beta-estradiol therapy and amyloid-beta deposition. Journal of Alzheimer’s Disease. 2016; 53 (2): 547-556.
  8. Kantarci K, Tosakulwong N, Lesnick TG, et al. Changes in brain structure three years after the end of menopausal hormone therapies in a randomized controlled trial: Kronos Early Estrogen Prevention Study (KEEPS). Alzheimer’s Association International Conference, London, UK. 2017.

The Importance Of Revamping The Guidelines For Alzheimer’s Disease

By | Blog Post, News

By Neelum T. Aggarwal, MD, Rush Alzheimer’s Disease Center, SWHR Interdisciplinary Network on Alzheimer’s Disease Member

An estimated 5.2 million Americans live with Alzheimer’s disease (AD). Of these Americans, 5 million are over the age of 65 years old. AD is the third leading cause of death in older adults, and is the only top 10 cause of death in the U.S. with no disease modifying treatment or proven treatment for prevention. 

Even with the statistics mentioned above, it is surprising that the actual diagnosing of the disease remains problematic. Not only is the clinical question regarding “Are there changes in thinking or memory?” not asked in many routine healthcare visits, many cases of dementia go undiagnosed or unclassified. This troubling trend, coupled with the staggering number of projected cases of dementia in the coming years, led the National Institute on Aging and the Alzheimer’s Association (NIA-AA) to partner and propose that a critical review of the existing research be conducted with the goal of recommending new updated diagnostic criteria and guidelines for AD.

In 2011, a series of articles was released from the NIA-AA Working Group. The resulting new diagnostic criteria incorporated two important changes: discussion of the early stages of AD, as well as the introduction of the terminology “presymptomatic Alzheimer’s disease;” and the importance of biomarker tests to aid in the diagnosis of AD.

Out With the Old (Guidelines) and in With the New

Previous guidelines for diagnosing dementia and AD relied heavily on a health care provider’s (HCPs) clinical judgment about the cause of a person’s symptoms based on reports from the individual, a spouse, family member, or friend, in addition to “data” obtained from the clinical evaluation (cognitive tests, a neurological exam, a brain scan, and blood tests). Often times however, the dementia diagnosis presented a clinical diagnostic challenge because clinical signs and symptoms, particularly early on, could be consistent with more than one cognitive syndrome. This challenge, coupled with variability in clinical knowledge and experience by the HCP in diagnosing and treating patients with dementia, and non-conclusive clinical tests that could signal a dementia, only added to the confusion surrounding the diagnosis and subsequent care for patients with cognitive disorders.

Alzheimer’s Disease in Three Stages

Enter the new criteria for AD that proposed three distinct stages: preclinical Alzheimer’s disease, mild cognitive impairment (MCI) due to Alzheimer’s disease, and dementia due to Alzheimer’s disease. The importance of this multistep staging system cannot be overstressed. It was the first time that a staging system for AD attempted to combine clinical symptoms with evidence of brain changes (via biomarkers). The proposed staging resulted from the mounting evidence of biomarker data that suggested AD begins before the development of clinical symptoms and that emerging technology could identify brain changes that precede the development of symptoms.

So, What Exactly Does Each Stage Mean?

Persons with preclinical Alzheimer’s disease have measurable changes in the brain, cerebrospinal fluid, and/or blood biomarkers that may indicate the earliest signs of the disease, but they have not yet developed symptoms such as memory loss. This preclinical or presymptomatic stage reflects our current thinking that AD-related brain changes can occur 20 years before symptoms occur. Although the criteria for this “preclinical stage” of AD are in place, it is not routinely being used by HCPs. More research in the area of biomarkers and their prognostic value as tests to predict the development of dementia needs to be done before HCPs begin to universally use this term and render a diagnosis of preclinical Alzheimer’s disease in their patients.

In contrast, MCI due to Alzheimer’s disease has gained more recognition among the medical community and the terminology is being increasingly used by HCPs. Individuals with MCI have mild but measurable changes in thinking abilities that are noticeable to the affected individual, work colleagues, or friends, but these symptoms are not severe enough to impact the individual’s ability to carry out everyday activities.

Dementia due to Alzheimer’s disease is the third stage in the disease classification. In this stage, persons typically have memory, behavioral, and other thinking changes that are severe enough to impair a person’s ability to function in daily life, and that are thought to be due to AD brain changes.

There is still more to be done in investigating new AD risk factors, discerning how biomarkers may assist in establishing the risk of dementia, establishing how risk factors vary by gender, and translating these findings to clinical practice. The Society for Women’s Health Research’s Interdisciplinary Network on Alzheimer’s Disease is committed to advocating for these goals in order to inform prevention, providing guidance for research, clinical trials, and policy. Click here to learn more about SWHR’s work in Alzheimer’s disease.

SWHR Engages Migraine and Women’s Health

By | Blog Post, Event, News

Migraine is the second leading cause of global disability, affecting 1.04 billion individuals worldwide and more than 47 million in the U.S. alone. Three times as prevalent in women compared to men, this debilitating disease continues to be under recognized.

The event’s speakers with Amy M. Miller, PhD, CEO of SWHR

On October 2, 2017, the Society for Women’s Health Research (SWHR®) convened interdisciplinary thought leaders at the George Washington University Milken School of Public Health for a panel discussion that included patients, practitioners, and the employer perspective.

“Only a fraction of individuals with migraine are appropriately diagnosed and treated,” explained panelist Jelena Pavlovic, MD, PhD, a neurologist at Albert Einstein College of Medicine. Patient advocate, Katie Golden, who experienced her first migraine when she was five years old, said she was lucky because her parents took her complaints seriously. However, her chronic migraine still resulted in her becoming disabled at age 30, causing her to drastically alter her career plans.

Despite migraine’s high prevalence, more education and deeper knowledge within the medical community is needed. The number of headache specialists in the U.S. is lacking significantly, said Dr. Pavlovic, with approximately one headache specialist for every 90,000 Americans with migraine. Five states currently have none.

The economic burden of migraine is staggering. In the U.S. alone, 113 million workdays are lost to migraine each year, costing employers more than 13 billion dollars. The costs of treating chronic migraine rise substantially when patients have one or more additional chronic conditions. Katy Spangler, senior vice president of the American Benefits Council, highlighted the role of emerging health policy concepts, such as value-based insurance design (VBID) that encourages patient utilization of high value services to drive better health and reduce costs. Spangler encouraged the migraine community to engage in benefit design and cost issues. “Let’s do a better job upfront, so people are healthier and happier, they’re more productive, and [everyone involved is] saving money.”

The public forum represents an expansion of SWHR’s successful scientific work, and enables additional, broader issues on migraine to be addressed. “SWHR looks forward to continuing to bring attention to these issues through the formation of a multi-year Migraine Network beginning this fall,” said SWHR President and CEO Amy Miller, PhD.

The goals of the future Migraine Network are to raise public awareness, change the perception of migraine, and to coordinate the diverse advocacy community with the intention of providing patients with tools to improve their healthcare. Furthermore, it will engage coverage, payment, and access policies. Such goals will be done through tangible educational materials, public forums, coalition building, publications, and advocacy activities.

SWHR is grateful for the support of the sponsors who made Migraines Matter: Beyond Burden to Value possible: Amgen, Eli Lilly, Novartis, and The Allergan Foundation.



The Society for Women’s Health Research Elects Roberta L. Gartside, MD, as Incoming Chair of Its Board of Directors

By | Blog Post, News, Press Release

Washington, DC (October 19, 2017)—The Society for Women’s Health Research (SWHR) announced the unanimous election of Roberta L. Gartside, MD, as the new Chair of its Board of Directors for 2018-2019. As a business leader with a strong commitment to nonprofit service, Dr. Gartside will lead the organization’s mission-based efforts to eliminate imbalances in care for women through science, advocacy, and education.

Dr. Gartside is a leading board-certified plastic surgeon in the Washington, D.C. metro area. She dedicates her practice to improving the function and appearance of her patients through the use of the most advanced aesthetic techniques and technologies. Dr. Gartside is passionate about her work and is committed to excellent patient care, believing that providing skill, support, and compassion are her main duties as a surgeon.

“SWHR is expanding its scope into disease and conditions that only or primarily impact women. Dr. Gartside is well-positioned to help the organization move from its foundation in science and advocacy into the practice of medicine,” said Amy M. Miller, PhD, president and CEO of SWHR.

Dr. Gartside is a fellow in the American College of Surgeons and also a member of the American Society of Aesthetic Plastic Surgery and American Society of Plastic Surgeons (ASPS). Previously, she was Vice President for Membership and Communications of ASPS, and the ASPS representative to the National Accreditation Program for Breast Centers (NAPBC). Locally, Dr. Gartside is a member of the National Capital Society of Plastic Surgeons and the Virginia Society of Plastic Surgeons. She also served as a trustee for Elizabethtown College, her alma mater for 14 years.

“Roberta has been steadfast in supporting our quest to advance discovery in women’s health, and her leadership will open many new doors of opportunity for SWHR,” said John J. Seng, the outgoing chair.

Dr. Gartside holds a Bachelor of Science from Elizabethtown College in Pennsylvania, and a Doctor of Medicine from Temple University School of Medicine in Philadelphia. She has completed residencies in general surgery at the Medical Center Hospital of Vermont, and plastic surgery at the George Washington University Medical Center in Washington, D.C. She is an author of several influential articles, including “The Biology of Human Malignant Melanoma.”

“I’ve been involved with the Society since its founding and have seen the organization evolve over the course of years to the standout nonprofit organization it is today and will continue to be in the future. It is my honor to lead its expansion into new areas of healthcare,” said Dr. Gartside.

SWHR leads the way in advocating for greater funding for women’s health research and for the study of biological differences between the sexes that affect disease, its presentation, and treatment; promotes the inclusion of women and minorities in medical research; pushes for the analysis of research data for sex and ethnic differences; and informs women, health care providers, and policymakers about women’s health issues.

A full list of the SWHR Board of Directors is available here.


The Society for Women’s Health Research Elects New Board Members

By | Blog Post, Press Release

Washington, DC (July 12, 2017)  The Society for Women’s Health Research (SWHR®) announced the election of two new members to its Board of Directors. Joining are Dawn Halkuff, Chief Commercial Officer at TherapeuticsMD; and Gretta Stone, Deputy Vice President of Policy & Research at the Pharmaceutical Research and Manufacturers of America (PhRMA).

To strengthen our leadership in women’s health research, SWHR welcomes these experts to our Board of Directors,” said Dr. Amy M. Miller, SWHR President and CEO. “Ms. Halkuff’s rich corporate background and Ms. Stone’s breadth of health policy knowledge will help further SWHR’s mission to advance women’s health research through science, advocacy, and education.”

Dawn Halkuff
Dawn Halkuff is the Chief Commercial Officer at TheapeuticsMD, a healthcare company focused on developing products exclusively for women. She has held numerous senior level commercial and marketing positions over 20 years. Most recently, she served as Senior Vice President of the Pfizer Consumer Healthcare Wellness Organization and a member of the Consumer Global Leadership Team. Ms. Halkuff was also commercial lead for sales and marketing of the Pfizer Women’s Health Division, focusing on the company’s reinvestment in hormone therapy treatment, including Premarin Vaginal Cream® and oral hot flash treatments. From 2005 to 2010, Ms. Halkuff was Head of Global Innovation at Weight Watchers International, where she created new weight-loss products, services, and solutions for women worldwide.

She holds a BA in Psychology from University of Connecticut and an MBA from Pennsylvania State University.

“Joining the SWHR Board of Directors is a natural fit as I share SWHR’s commitment to advancing women’s health research and furthering the development of innovative therapies for women,” said Ms. Halkuff. “I am excited to bring my passion and expertise in women’s healthcare to the Board as SWHR works to improve women’s health” she said.

Gretta StoneGretta Stone
Gretta Stone is the Deputy Vice President of Policy & Research at PhRMA, where she manages a range of issues related to the research and development process, including U.S. Food and Drug Administration regulations, the value of medicines, and personalized medicine. In her more than 12 years at PhRMA, she has also worked extensively on orphan drugs, the biopharmaceutical pipeline, the research ecosystem, the cost of medicines, and marketing and promotion. Gretta has authored many PhRMA reports and publications, including the annual “Biopharmaceutical Industry Profile,” an overview of the sector and a go-to source of data on the industry.

Prior to joining PhRMA, Gretta worked in a lab researching language and the brain at Georgetown University, where she received a BS in biology.

“SWHR’s advocacy for policies that improve understanding of the difference between sexes and that remove barriers to care have made a real difference in women’s health,” said Ms. Stone. “But many opportunities remain and I look forward to helping SWHR drive needed policy change to enhance women’s health,” she said.

SWHR leads the way in advocating for greater funding for women’s health research and for the study of biological differences that affect disease; promotes the inclusion of women and minorities in medical research; pushes for the analysis of research data for sex and ethnic differences; and informs women, health care providers, and policymakers about women’s health issues.


A full list of the SWHR Board of Directors is available here: http://swhr.org/about/board-of-directors/

Sleep, Pregnancy, And Your Future Health

By | Blog Post

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.


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.

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

By | Blog Post

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.


  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).

SWHR Convenes Leaders in Health Policy for Second Annual Awards Dinner Symposium: The State of Women’s Health

By | Blog Post

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 Hot Flashes: Middle of the Night Sleep Intruders

By | Blog Post

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.


  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.


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

By | Blog Post

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.


  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.
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