Women’s Health Research at Yale to fund four new studies

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A study of factors affecting elderly women drivers is one of four studies funded by Women's Health Research at Yale. (Photo by CDC/Amanda Mills)

Women’s Health Research at Yale has awarded funding for studies to tackle skin cancer, autism, chronic urinary tract infections, and challenges faced by elderly drivers.

With seed money through this year’s Pilot Project Program — including the second-ever Naratil Pioneer Award recipient for research on the verge of a significant breakthrough — the researchers aim to answer questions vital to improving women’s health.

These questions include: How can doctors better help women suffering from recurring skin cancer in their legs? What can be done when 25% of urinary tract infections recur chronically even after appropriate antibiotic treatment? How can an aging woman or her family better determine when it’s no longer safe for her to drive a car? And: What is the best way to treat girls with autism?

“This year’s recipients represent trailblazers in their fields who seek answers to critical questions that will advance our understanding of women’s health issues and the best practices to treat these issues,” said Dr. Carolyn M. Mazure, director of Women’s Health Research at Yale.

“Every year presents a challenge for our scientific review committee to select among a pool of stellar research projects poised to offer practical implications for the health of women. This year’s recipients rose to the top with elegant studies designed to help meet ever-more urgent needs,” she added.

Urinary tract infections

Toby C. Chai, M.D., professor and vice chair of research in urology, will receive the Wendy U. and Thomas C. Naratil Pioneer Award to determine if localized, targeted application of estrogen can provide natural protection to prevent and treat chronic urinary tract infections.

One out of two women experience urinary tract infections (UTIs) in their lifetimes, and UTIs recur 25% of the time even after appropriate antibiotic treatment.

A recent survey revealed 4.2 million emergency room visits for UTIs, with the largest number among women between the ages of 45 and 54, suggesting menopause as a possible factor for the increased incidence.

Chai’s team will seek to determine if the introduction of estrogen directly to the bladder, as opposed to systemic use of estrogen, can protect against recurring UTIs. Using a mouse model — the first step in determining the biological mechanisms at play — Chai hopes to lay the groundwork for human clinical trials and an approved treatment that can save lives.

“We’re running out of antibiotics,” Chai said. “We utilize them so frequently the bacteria have become smart. They develop resistance quickly. We really have to open up new avenues to be able to find new treatments for infections.

By proving the effectiveness of this new treatment for UTIs in mice, Chai hopes to avoid fears of estrogen therapies that can lead to breast and uterine cancers, blood clots, and pulmonary embolisms.

Skin cancer

Christine J. Ko, M.D., associate professor of dermatology and pathology, aims to identify a biological marker to predict the growth rate and recurrence of cutaneous squamous cell carcinoma. Her team’s current target is a mutated gene the researchers believe marks the difference between a slow-growing cancer and a more aggressive one.

With co-funding from the Yale Cancer Center, the new study will focus on skin cancer in women’s legs. Ko anticipates that the team’s approach will identify other possible indicators to pursue and eventually develop a clinically practical biomarker to predict the growth of this type of cancer.

“Although these cancers don’t tend to be aggressive, currently there is no way to know if this type of cancer is slow-growing or more aggressive, potentially infiltrating the bone or otherwise becoming life-threatening,” Ko said. “Consequently, right now all of these lesions require removing the thin skin on a lower leg, leaving a large hole that is difficult to heal or replace with a graft.”

Ko hopes her study will lead to less invasive treatments and better outcomes.

“If you do the biopsy and find that it’s not going to be that aggressive, we can scrape and burn it lightly,” Ko said. “We could treat it in a less aggressive manner, if we knew it was not going to cause the patient harm.”

Autism

Pamela Ventola, Ph.D., clinical director of the Center for Translational Developmental Neuroscience at the Yale Child Study Center, will test — for the first time — the efficacy of an autism therapy for girls, bringing together leaders in the fields of autism spectrum disorder treatment, maternal mental health, and neuroscience.

Ventola’s study also represents the first attempt to examine the malfunctioning brain circuitry underlying autism by manipulating brain activity such as those related to social reward and emotion regulation.

Boys are diagnosed with autism almost four times as often as girls, a discrepancy that is poorly understood. Researchers have historically excluded girls from studies of children with autism spectrum disorder or included so few as to make it impossible to draw meaningful conclusions. Now for the first time, investigators seek to understand how girls with autism respond to treatment.

“Girls with developmental disabilities have been largely ignored in terms of the research in the field,” Ventola said. “Right now we are assuming girls are the same as boys.”

Ventola said that recent research has shown girls can have high-functioning autism and subtle social symptoms that doctors might miss.

“How can we best treat girls?” Ventola said. “And how do their brains respond to treatments? Do they respond similarly to boys?”

In addition, the study aims to investigate how mothers react to their daughters’ treatment to better understand how to support mothers of girls with autism.

“Parenting a child with autism is tremendously difficult, and there’s been very little focus on mothers,” Ventola said. “If they are not the primary caregiver, they are the primary worrier. We need to learn how to support these children in a family context.”

Elderly drivers

Richard A. Marottoli, M.D., M.P.H., professor of medicine, will seek to identify the cognitive, health, and environmental factors in elderly women that predict adverse driving events such as crashes and tickets, leading the way toward interventions that can enhance their safety and public safety.

“Older women are more likely to live alone and feel compelled to keep driving,” said Mazure. “Moreover, women suffer more from osteoporosis, leaving them more at risk of a serious or fatal injury from a crash. Dr. Marottoli’s study will help shed light on this growing issue and lead the way toward solutions.”

By 2030, one-fifth of all drivers will be at least 65 years old. Currently, 73% of women over 65 still drive. Between 1990 and 2020, the distances traveled by older female drivers will increase by 500%.

And yet no studies of cognitive function and associated brain structures have focused on older women — until now.

“Women live longer and have transportation needs for a longer time,” Marottoli said. “The question is: Is there a gender difference or is there not? I think there are some differences.”

In his clinic, said Marottoli, he often struggles to help patients determine when they are no longer able to drive. When advised against driving any longer, patients fear an end to a lifetime of independence, he noted.

“As soon as you open the discussion about driving, patients know what the implications for that are,” Marottoli said. “It’s not a determination that should be made lightly.”

Marottoli sees his study as a source of crucial data for clinicians and families to tailor decisions about driving cessation toward each patient as much as possible, based on her individual risk so as to make that transition with a minimal impact on her life.

“We try to give people as much information as possible and help them in the decision process,” he said. “The more information you have, the more you can help them in a difficult discussion.”

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