2020 Awardees

Estrogen and the circadian clock in women with asthma

Sex disparity in asthma exists across the lifespan. Understanding mechanisms that contribute to chronic airway disease in women from post-puberty through the postmenopausal years could identify novel therapeutic targets and treatment strategies in women.

Our work puts forth the idea that sex hormones and circadian rhythm are intertwined and that targeting circadian clock biology may be a therapeutic approach, as circadian disruption is strongly associated with airway diseases such as asthma.

Assessment of sleep disruption in women with bilateral salpingo-oophorectomy

Frequency and severity of sleep disturbances increase dramatically during the menopause transition and contribute to aging-related health deterioration in women. However, it is unknown whether sleep difficulties are exacerbated in women who are exposed to premature menopause due to removal of both ovaries (bilateral oophorectomy) before natural menopause. The goal of this research study is to compare objective and subjective sleep characteristics in women who have undergone bilateral oophorectomy before natural menopause with women who did not undergo this procedure.

Preventing the transition of cutaneous to systemic lupus erythematosus

  • Ali A. Duarte Garcia, M.D.
  • Assistant Professor of Medicine
  • Rheumatology
  • Funded by the Mayo Clinic Women's Health Research Center
  • (2/2020-1/2022)

Women are affected by systemic lupus erythematosus (SLE) up to 10 times more frequently than men. Patients with SLE have substantial morbidity, disability and a threefold increase in mortality, compared with the general population. This heterogeneous autoimmune disease can affect any organ; however, there is a form of the disease where the symptoms are restricted to the skin: cutaneous lupus erythematosus (CLE). It has been recognized that patients with CLE can transition to SLE and is believed the majority will transition in the early years of the disease, providing a unique opportunity for intervention in a readily identifiable population at risk of progression.

Given the severe consequences of SLE, the identification of modifiable risk factors for transition from CLE to SLE is of the utmost importance. This study will define the rate and time of transition from CLE to SLE as a window of opportunity for therapeutic interventions and determine the impact that oral contraceptives or postmenopausal hormone use, a very common lifestyle factor, has in the progression of CLE to SLE.

Cognitive effects of pituitary-ovarian hormones in menopause

  • Juliana (Jewel) M. Kling, M.D., M.P.H.
  • Associate Professor of Medicine
  • Chair of Women's Health Center, Arizona
  • Jointly funded by the DREAMS fund and the Mayo Clinic Women's Health Research Center
  • (2/2020-6/2021)

Memory problems are commonly reported during the menopausal transition. However, questions remain about the effect of menopausal hormone therapy (MHT) on memory, cognition and brain structure. Furthermore, it is unclear if or how pituitary and ovarian hormones influence these clinical outcomes.

This project aims to evaluate pituitary ovarian hormone levels, cognitive outcomes and brain structure findings in menopausal women participating in the continuation to the Kronos Early Estrogen Prevention Study (KEEPS) approximately eight years after they completed four years of MHT or placebo. Findings will provide additional insight into the mediators of the hormone responses and the impact of hormonal modulation of aging including cognitive decline in postmenopausal women.

Evaluating the prevalence and implications of obstructive sleep apnea among pre- and postmenopausal women of Somali origin

  • Essa Mohamed Ph.D., and Virend Somers, M.D., Ph.D.
  • Department of Cardiovascular Diseases
  • Funded by the Mayo Clinic Women's Health Research Center
  • (2/2020-1/2022)

Obstructive sleep apnea (OSA) disproportionately impacts individuals of African ancestry when compared with those of European ancestry. In addition, there is an underreporting as well as underdiagnosis for OSA among African Americans. Considering OSA is a public health issue, it is critical to institute measures to screen Somali American women for OSA, to identify mechanistic links to comorbid disease and to establish effective measures to improve long-term quality of life.

Understanding the pathophysiology of how OSA impacts the development of cardiovascular disease among Somali American women will help develop effective and sex-specific treatment modalities for women historically underrepresented in clinical research.

Understanding sex-specific effects of abrupt endocrine disruption on physical activity, and bone and muscle health

Many women undergo premenopausal bilateral oophorectomy to prevent ovarian cancer. However, the resulting abrupt endocrine disruption may contribute to accelerated aging processes and lead to increased frailty-related diseases, such as osteoporosis and sarcopenia, which result in poorer physical function.

This study focuses on the effects of a history of premenopausal bilateral oophorectomy on daily physical activity, measured using wearable sensors on the ankles, and its role in bone and muscle loss with aging.

Mayo Posture Positivity Power Program (MayoP4) for active and aging women in communities: A 15-minute multimodal intervention to prevent frailty

  • Nagai Takashi, M.D. (original PI)
  • Nathan D. Schilaty, D.C., Ph.D. (current PI)
  • Assistant Professor of Orthopedics and Physical Medicine and Rehabilitation and Physiology
  • Funded by the Mayo Clinic Women's Health Research Center
  • (2/2020-6/2021)

Musculoskeletal conditions are the leading cause of disability, frailty and mortality in aging women, yet the topic is given little consideration in women's health care. Exercise is essential and effective medicine for management and prevention of obesity, lack of physical activity, chronic disease, frailty, and mental stress/anxiety/depression without the side effects from drug use. Interestingly, less than 1% of all performed biomedical research focuses on physical interventions and community implementation. More recently, multimodal interventions with physical, postural, mindfulness and power exercises have demonstrated improvements to both physical and mental health.

To expand the recent trend in multimodal intervention, this project will examine the effects of a community-based multimodal intervention on physical, psychological, cognitive, social and environmental characteristics in aging women. Further, it will establish normative values and interrelationships of health outcomes.

The role of PHLPP protein phosphatases in sex-specific progression of osteoarthritis

Osteoarthritis is a prevalent, painful disease that primarily affects postmenopausal women. Targeting PHLPP protein phosphatases may slow the progression of osteoarthritis. However, preliminary studies have focused exclusively on PHLPP and osteoarthritis in males. This project will interrogate the sex-specific regulation of osteoarthritis and characterize the role of PHLPPs in female osteoarthritis.

Biological and therapeutic investigation of sex differences in valvular stenosis

  • Bin Zhang, M.D.
  • Assistant Professor of Surgery
  • Cardiovascular Surgery Research
  • Funded by MAE Private Foundation
  • (2/2020-1/2022)

The overarching goal of our program is to create novel strategies that slow or halt progression of age-associated cardiovascular diseases and delay or eliminate the need for surgical intervention. We believe understanding sex differences in the progression of aortic valve stenosis is pivotal in these efforts.

By combining our abilities to perform the precise and detailed characterizations of the sex-specific molecular underpinnings of disease with our strong track record in drug development and the successful execution of clinical trials, we aim to develop individualized, sex-specific treatment strategies for men and women that dramatically improve and extend a patient's quality and quantity of life.