Posted by on July 1, 2010 - 10:35am

Women who measure their peak heart rates for exercise will need to do some new math, as will physicians giving stress tests to patients.  A new formula based on a large study from Northwestern Medicine provides a more accurate estimate of the peak heart rate a healthy woman should attain during exercise. It also will more accurately predict the risk of heart-related death during a stress test.

“Now we know for the first time what is normal for women, and it’s a lower peak heart rate than for men,” said Martha Gulati, MD, assistant professor of medicine and preventive medicine and a cardiologist at Northwestern Medicine. “Using the standard formula, we were more likely to tell women they had a worse prognosis than they actually did.”   Gulati is the lead author of a study published June 28 in the journal Circulation.

“Women are not small men,” Gulati added. “There is a gender difference in exercise capacity a woman can achieve. Different physiologic responses can occur. ”   Gulati was the first to define the normal exercise capacity or fitness level for women in a 2005 study.

The old formula -- 220 minus age -- used for almost four decades, is based on studies of men. The new formula for women, based on the new research, is 206 minus 88 percent of age.   At age 50, the original formula gives a peak rate of 170 beats per minute for men and women. The new women’s formula gives a maximum heart rate of 162 beats for women.  Many men and women use their peak heart rate multiplied by 65 to 85 percent to determine their upper heart rate when exercising.

“Before, many women couldn’t meet their target heart rate,” Gulati said. “Now, with the new formula, they are actually meeting their age-defined heart rate.”    The new formula is trickier to calculate, Gulati acknowledged, but is easily determined with a calculator. She currently is working on an iPhone application for a quick calculation.

The new formula is based on a study of 5,437 healthy women ages 35 and older who participated in the St. James Women Take Heart Project, which began in the Chicago area in 1992.    With the new formula, physicians will more accurately determine if women are having a normal or abnormal response to exercise.    “If it’s abnormal, that’s a marker for a higher risk of death,” Gulati said. “Maybe we need to talk about whether you exercise enough and what we need to do to get it into the normal range.

“We need to keep studying women to get data applicable to women,” Gulati said. “It’s important to not get complacent that we have data on men and assume women must be the same. They’re not.”

Gulati’s senior author on the study was the late Morton Arnsdorf, MD, professor emeritus and associate vice chairman of medicine and former section chief of cardiology at the University of Chicago.

Posted by on June 15, 2010 - 10:19am

An article was released in the June 10, 2010 edition of the well-respected journal, Nature, that raises the question of doing research studies on pregnant women.    Women  get colds, the flu, infections and other diseases during their pregnancies that have nothing to do with their mom-to-be status.   Many women simply "toughen it out" hoping their condition is just a virus that will run its course.   Other times, they rely on their obstetrician's experience with other patients who may have been prescribed an antedote that the physician has used successfully in her/his practice, but has not actually been studied in well-designed research studies that included pregnant women.

Are these women being shortchanged?   Are they simply not supposed to get sick through their pregnancy?     Here's a bit of history:   It wasn't until 1994, that the Food and Drug Administration (the regulatory agency that approves drugs for safety and effectiveness)  lifted the ban on inclusion of women with childbearing potential from the early clinical trials.    This ban had been in place since 1977 and not only excluded pregnant women, but "women who had childbearing potential" and certainly impacted the number of women participating in clinical studies.   No wonder our knowledge of sex differences in disease remains inadequate!

An important and legitimate concern, of course, is the safety of a potential fetus.    Anyone over age 50 recalls the thalidomide (a drug prescribed for morning sickness)  tragedy of the late 50s/early 60s that resulted in far too many babies, especially in Europe, being born with deformities.   While this tragedy alerted us to potential in-utero harm, it also slowed the progress we need to be sure tragedies of this nature never happen again while collecting important data on drug use in women.    The author of the Nature article  provides a logical strategy that should be considered and supported by all women's health activists. Click  Pregnant Women Deserve Better to view article.

Posted by on June 10, 2010 - 12:16pm

According to the World Health Organization, alcohol is one of the most significant risk factors for diseases including chronic conditions like cancer, diabetes, and heart disease.  Compared with men, women become more cognitively impaired by alcohol and are more susceptible to alcohol-related organ damage.    Women develop damage with less intake and  over a shorter period of time than men.   When men and women of the same weight consume equal amounts of alcohol, women have higher blood alcohol concentrations.   This is due in part because women have proportionately more body fat and a lower volume of body water compared with men of similar weight. This leads to women having a higher concentration of alcohol because there is less volume of water to dilute the alcohol.

in women, alcohol metabolizes slower in their stomachs and upper intestines allowing more alcohol to reach the blood stream and other organs than in men, leading to increased organ damage.  Women have more severe complications related to alcohol abuse than men including developing alcohol dependency more quickly.   Damage resulting from alcohol dependency  that is more severe in women includes liver damage (hepatitis/cirrhosis), premature death from cardiovascular conditions, cognitive and motor function decline,  and fertility issues.

Age seems to matter.  Older women have even less body water, a decreased tolerance for alcohol, and an even slower metabolism rate for alcohol.

Source:  Substance Abuse Treatment:  Addressing the Specific needs of Women. HHS Publication No.  (SMA) 09-4426.  2009

Posted by on June 1, 2010 - 8:56am

Biological differences between the sexes could be a significant predictor of responses to vaccines, according to researchers at the Johns Hopkins Bloomberg School of Public Health. They examined published data from numerous adult and child vaccine trials and found that sex is a fundamental, but often overlooked predictor of vaccine response that could help predict the efficacy of combating infectious disease. The review is featured in the May 2010 issue of The Lancet Infectious Diseases.

“Sex can affect the frequency and severity of adverse effects of vaccination, including fever, pain and inflammation,” said Sabra Klein, PhD, lead author of the review and an assistant professor at the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology. “This is likely due to the fact that women typically mount stronger immune responses to vaccinations compared to men. In some cases, women need substantially less of a vaccine to mount the same response as men. Pregnancy is also a factor that can alter immune responses to vaccines.”

Researchers conducted a review of existing literature on several vaccines including yellow fever, influenza, measles, mumps and rubella, hepatitis and herpes simplex to obtain evidence of the difference in responses between women and men. They also examined the effect hormonal changes that occur during pregnancy have on vaccine efficacy. Researchers found that despite data supporting a role for sex in the response to vaccines, most studies did not document sex-specific effects in vaccine efficacy or induced immune responses.

“Understanding the biological differences between men and women to vaccines could have led to better distribution of the 2010 H1N1 vaccine during the early months. Our review of the literature found that healthy women often generated a more robust protective immune response to vaccination when compared to men,” said Andrew Pekosz, PhD, associate professor at the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology. “An understanding and appreciation of the effect of sex and pregnancy on immune responses might change the strategies used by public health officials to start efficient vaccination programs, optimizing the timing and dose of vaccines so that the maximum number of people are immunized.” added Klein.
“The Xs and Y of Immune Responses to Viral Vaccines” was written by Sabra L. Klein, Anne Jedlicka and Andrew Pekosz.

Source:   Johns Hopkins Newscenter

Posted by on March 31, 2010 - 1:39pm

“By not studying sex differences, researchers could be missing out on potential new treatments for both men and women”,  says Rhonda Voskuhl.  Finally, Science Magazine is speaking our language!  I felt like I was reviewing talking points from one of my own presentations when reading the NewsFocus article titled, “Of Mice and Women: The Bias in Animal Models”  http://www.sciencemag.org/cgi/content/full/327/5973/1571.  Unfortunately, it is no surprise to us at the Institute for Women’s Health Research that basic scientists are not designing studies that include both male and female animal models.  One reason our Institute was established was to break down this barrier by providing funding to the NU research community to design studies with sex and gender in mind, in addition to stressing the importance of analyzing results based on sex.

You might be asking, it’s 2010, why would researchers only study one sex?  Cost and ease.  It’s cheaper to house less animals in a research facility, the NIH may not provide enough funds to conduct studies in both sexes, researchers don’t want to deal with the estrous cycle (which in rodents is every 4 days) and the data is “cleaner” because the hormones responsible for the estrous cycle DUE effect biology.

A few important points this article highlights:

  • The vast majority of journal articles published in 2009 reported results of research in male animals only.
  • Many articles fail to report the sex of subjects at all.
  • In studies that include both males and females, 2/3 fail to analyze the results based on sex.

The results from animal studies in basic science laboratories are what help determine the design of clinical research studies in humans.  If we don’t include female animals from the start, then male-only data is what gets transferred into the clinical arena.  Then, there is the issue of recruiting equal numbers of men and women into clinical trials.  If trials are predominantly made up of male participants then once again, the results that get published and become the foundation for drug and medical device development are applicable in men, but may not (and often times do not) apply to women.

What suggestions are provided in the article?

  • If the NIH set guidelines to channel limited resources to areas that show clear sex differences such as cardiovascular disease or pain, researchers would have to include both sexes in order to get money.
  • Mining NIH data from large patient trials could help identify sex differences in people that would be worth studying in animals.
  • The Office for Research on Women’s Health could provide targeted funding opportunities.
  • Pressure from academic journals to adopt a set of guidelines for studies using animals, including the expectation to provide rationale for studying only one sex and the implications for not studying the other, could force authors go back to the drawing board.

We hope that articles similar to this will continue to be published in high impact journals and finally “get scientists thinking about the issue of sex bias” and its implications for how we practice medicine today.

Posted by on March 30, 2010 - 1:13pm

Yesterday, I started writing a blog explaining why sex and gender research was important.  I got bogged down in historical background, mandates, and the usual boring facts and justifications.   While doing this, my desktop binged and one of several daily notices from federal agencies popped up on my computer.   Since I was having writer's block, I decided to check these new emails....and BINGO....there is was!     A news release from the National Institute on Drug Abuse (NIDA), one the Institutes at the  National Institutes of Health (NIH).   The title of the press release was "Common Mechanisms of Drug Abuse and Obesity".   It summarized a study funded by NIDA  that will appear in a prestigious journal in May.   The study found that some of the same brain mechanisms that fuel drug addictions in humans accompany the emergence of compulsive eating behaviors and the development of obesity in animals.  The investigators found that when they gave rats access to varying levels of high-fat foods, they found unrestricted availability alone can trigger addiction-like responses in the brain, leading to compulsive eating behaviors  and the onset of obesity.  According to one of the study authors, "The results of this study could provide insight into a mechanism for obesity".

This was all very interesting but what popped out at me was a sentence in the fifth paragraph:   Researchers conducted this study in three groups of male rats over a 40-day period. What about female rats!  Do they behave the same?    Will this study translate to a human study before these findings are tested in female rats?   What we do know is that obesity rates are higher in women.   How many women reading this have experienced a change of eating urges during their periods? Do hormones play a role here?

Why am I upset?    It took decades of advocacy from women to create mandates at the NIH, the major funder of health research, that requires the inclusion of women in federally funded research studies.  Recently, there has been a growing debate on whether or not researchers are adequately meeting this mandate.   While there are more women's cancer studies (that may be inflating the % of women who are in studies), diseases like heart disease still do not have equal representations of men and women in clinical trials.    This mandate does not trickle down to animal studies, allowing researchers to continue to do basic science work in male animals that are, after all, "easier" (Translated:   they don't have complicated hormone cycles).   Too many studies have been conducted in males (animal and human) over the last few decades and the results applied to the whole population--sometimes with detrimental effects.  The Adverse Reporting system at the FDA has many more reports of adverse effects of drugs in women than in men......has anyone asked if these drugs have been adequately tested in women???

So, what needs to be done?    The inclusionary mandates for research studies requiring both sexes, need to include animal studies.   After all, isn't it much cheaper to do preliminary studies in animal models BEFORE they are applied to humans?  Researchers also need to report findings by sex....even if the answer is "they are the same".   Is anyone else asking these questions? Have women really come 'a long way'?

Posted by on March 19, 2010 - 9:53am

In recognition of Poison Prevention Week (March 14-20), the Center for Disease Control (CDC) is highlighting the growing issue of unintentional drug poisoning in the United States.   More than 26,000 deaths from unintentional drug poisoning occurred in the U.S. in 2006.  Opioid pain medications (e.g., oxycodones and methadone) were involved in more than half of these deaths.  In recent years, this cause of death has more than doubled between 1999 and 2006.   In 2006, 17,740 drug overdose deaths occurred among males and 8,660 among females.  Male rates exceed females rates in every age group.    However, male rates have doubled and female rates have nearly tripled since 1999.  In response to this growing problem the CDC has developed an issue brief titled Unintentional Drug Poisoning in the United States.

Posted by on February 15, 2010 - 10:05am

We realize that Thursday nights are jam packed with all sorts of great TV shows, but hopefully you were able to set the DVR for the WTTW series Health Secrets:  What Every Woman Should Know.  The 4-part TV series was hosted by Paula Zahn and sponsored by Northwestern Memorial Hospital and Alberto Culver.  Each one-hour program was aimed at addressing women's health needs at all stages of life. Topics ranged from vaccinating young girls (and boys) against HPV to Oncofertility to the importance of clinical research participation to the serious risk of heart disease and stroke in women.  No doubt each show was full of important and useful health information!  If you missed the series or do not get WTTW, you can watch segments from all the shows and obtain any information you need online at http://www.wttw.com/main.taf?p=1,57.

Over the past 4 weeks, an underlying theme was made pretty apparent - we just don't know enough.  In order to achieve the goal of personalized medicine, we must first better understand the differences in health and illness in men and women.  As we continue to conduct research that will bring about the next medical breakthroughs we need to focus on the necessity of educating the population about the clinical research process and why participation is key.  The Illinois Women’s Health Registry (https://whr.northwestern.edu), highlighted in show #3, serves as a resource for research and education that advances scientific knowledge of sex- and gender-based differences in health and disease.  If you want to observe what a powerful tool this Registry is becoming, please view the video below.

[video http://www.wttw.com/main.taf?p=72,9,2&pid=Fan7kByLCJDnJJaChFFiamvET7d_zFi9 here]

Both Drs Woodruff and Bristol-Gould are featured, in addition to a Registry participant who was interviewed about her experiences while enrolled in a knee osteoarthritis study.

If you haven't already enrolled, please get involved today.  https://whr.northwestern.edu

Posted by on January 20, 2010 - 1:56pm
Melina Kibbe honored at White House

Melina Kibbe honored at White House

Melina Kibbe, M.D., associate professor at Northwestern's Feinberg School of Medicine, vascular surgeon at Northwestern Memorial Hospital and co-chief of the vascular surgery service and director of the Vascular Laboratory at the Jesse Brown VA Medical Center recently received the Presidential Early Career Award for Scientists and Engineers (PECASE) at the White House.   This is the highest honor given by the U.S. government to outstanding scientists and engineers who are in the early stages of their research careers.

Her current research portfolio was primed, in part, by two Pioneer Awards the Institute for Women's Health Research (IWHR) awarded Dr. Kibbe and her postdoctoral fellow in 2008 and 2009, respectively.  Her research focuses on preventing vascular injury and scarring in blood vessels following stent surgery.   It wasn't until Dr. Kibbe  ran into Dr. Teresa Woodruff,  IWHR Director, a few years ago, who asked Kibbe if she was including female animals in her research, that she gave it much consideration. After that meeting, Kibbe searched publications in her field that included sex as a variable and she found there was very little.   With her Pioneer Awards, she proposed to include male and female animal models to study the benefits of nitric oxide (NO)-based therapies following stent surgery and found that the effect was totally different between the sexes!

The Pioneer Awards were developed by the IWHR to encourage researchers to include sex and gender analyses in their studies, and the work done in the Kibbe lab demonstrates how a small amount of funding targeted to sex-based research can produce startling results and change a whole field of study.   The immeasurable aspect of the PECASE award that Dr. Kibbe received is the invaluable  publicity it will give her research.  This may help focus on the importance of including sex variables in future vascular research and open doors to new collaborations and larger funding.

Posted by on October 14, 2009 - 9:27am

Scope                                                                                                                                                           trophy

There is an enormous scientific knowledge gap regarding the sex- and gender-based differences in human experiences of health, symptom manifestation, the diagnosis of illness, and the treatment of disease.  This affects the health of men and women and erodes the value of our biomedical dollar.  In working to close this gap the Institute for Women’s Health Research has developed the Pioneer Award funding mechanism to provide seed grants ($25,000 each) to investigators who either currently study, or would like to initiate new research focusing on, the sex and gender determinants of health and disease.  We strive to provide the catalyst that will encourage the Northwestern community to take the lead in designing and analyzing experiments based on sex.  The knowledge gap will tighten with our continued efforts to help the research community (researchers, NIH, FDA and IRBs) transform their practices to a system that highly values sex as an important research variable.  In turn, this transformation will translate into optimal care for both men and women.

Specifically this program:

  • Funds early career investigators to conduct pilot studies that will help build their portfolio enabling them to become competitive for larger, federal grants.
  • Provides a mechanism for senior researchers to mentor young scientists who are interested in sex- based research by providing funds to support these young investigators to work in their clinic or lab.
  • Advances our knowledge of women’s health through innovative research and a collaborative spirit that allows researchers to “think outside the box”.

As we enter the third year of issuing grants, it is becoming clear what an impact these research dollars are making on women's health at Northwestern University.  Accomplishments from the 2008 round of funding are summarized below.

Real Impact – Key Areas

Sleep in Women

  • Dr. Turek's group discovered that hormone replacement restores sex differences in sleep observed in mice, in addition to demonstrating that the hormonal state of animals is critical to the sex differences observed in the responses to challenges such as stress or sleep deprivation.  This funding trained several early investigators, one moved onto a career as Program Director at NIH, another is now professor at Moorehouse School of Medicine.  This work has generated two published manuscripts and one manuscript under revision, as well as the submission of four research proposals (R03, RC1, March of Dimes and Burroughs Wellcome) and two fellowship proposals.

Peripheral Vascular Disease in Women

  • Dr. Kibbe's group demonstrated in rodents that sex and hormone status are important factors in evaluating vascular injury, neointimal hyperplasia, and the benefits of nitric oxide (NO)-based therapies.  Male and female animals require different dosing of NO in order to inhibit neointimal hyperplasia, and this is likely attributable to differences between males and females at the cellular level.  Furthermore, castrated animals require higher doses of NO in order to achieve similar efficacy compared to hormone-intact animals.  This funding has changed the direction of Dr. Kibbe’s research, as Dr. Kibbe’s laboratory is now routinely studying the role of potential vascular therapies in both sexes.  Dr. Kibbe was recently awarded a Presidential Early Career Award for Scientists and Engineers.  This award has also provided mentorship and support for a young investigator, Dr. Hogg, to work in Dr. Kibbe's lab and pursue similar research.  Data generated thus far has led to one manuscript submission and two manuscripts in preparation for submission.

Infectious Disease in Women

  • Dr. Scarsi's group is developing the first available population-based pharmacokinetic model in HIV-infected pregnant women, thus furthering our pharmacologic management of HIV-infected women including gender differences in antiretroviral efficacy and toxicity.  Once enrollment in the study is complete, and data is analyzed, external funds will be pursued to expand analysis over the lifetime of HIV-infected women.

Mental Health and Neuroscience in Women

  • Dr. Gollan wrote and issued a clinical protocol entitled “Standard of Care for Detection of Perinatal Depression” that serves as a guide for all Northwestern University-affiliated OB/GYN physicians in the Prentice Ambulatory Clinic, Northwestern Memorial Faculty Foundation, and Northwestern Memorial Physician’s Group to screen and triage patients who report perinatal depression.
  • Dr. Gollan founded the Women’s Behavioral Health Services in Northwestern Memorial Faculty Foundation (Psychiatry), a new clinic offering pharmacotherapy and psychotherapy for women who are pregnant or postpartum.
  • Dr. Gollan's group is developing the first model to examine the cognitive, affective, clinical and biological variables that contribute to the onset of depressive symptoms during the postpartum phase.  One R01 application will be submitted based on this work in February 2010.
  • Dr. Woolley's group has determined that all commercially available ERβ antibodies are not specific.  Alerting the research community who have routinely used these reagents in publications and grant proposals is necessary to prevent additional investigators from drawing incorrect conclusions from faulty reagents.  One manuscript is in preparation describing these findings .
  • Dr. Woolley's group discovered a novel new mode of estrogen action in the brain region important in learning and memory, anxiety/depression, and seizure activity in epilepsy.  After further experiments are conducted a manuscript describing the findings and an R21 or R01 will be submitted.

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