The influence of gender on disease

Over the centuries, scientists have argued that men’s brains must be more powerful because they are larger than women’s brains. But does size matter? Newer studies have found that the differences between men and women are much more complicated than the size of the brain. Sex is not related to a particular type of brain and we are not born with brains stamped male or female, containing little pink or blue – or grey – cells. Although expert opinion varies in terms of what makes male and female brains different – not better or worse, just different – the overall consensus is that the brain contains a mix of both male and female characteristics as unique as our individual fingerprints.

The differences between men and women are determined by very complex interactions at the cellular level, including differences in brain structure, gene expression on X and Y chromosomes, a higher percentage of body fat in women, hormones, gut physiology, social experiences, and more. According to the Institute of Medicine, every cell in the body has a sex, which means that women and men are different even down to the cellular level. This also means that diseases, treatments and chemicals will affect the sexes differently.

These differences not only influence personality traits, but also the prevalence and response to treatment of particular diseases that are likely to ail men and women. For instance, sex and gender differences in cardiovascular diseases are well-investigated and there is strong evidence that men and women face different risk factors and have different treatment outcomes.

According to the American Heart Association’s journal Circulation, women’s heart attacks may have different underlying causes, symptoms and outcomes than men’s. Despite some improvements in the rate of cardiovascular deaths over the last decade, women still fare worse than men after a heart attack and heart disease in women remains underdiagnosed and undertreated.

Of course, cardiovascular diseases are by no means the only area in which men and women differ in their susceptibility to, and survival of, disease. Because gender affects a wide range of physiological functions, it has an impact on a wide range of diseases and conditions. In addition to “women only” health conditions, three times as many women suffer from autoimmune diseases as men and women are more susceptible to Alzheimer’s Disease, chronic fatigue syndrome, osteoporosis, diabetes, anxiety and depression, urinary tract disorders, irritable bowel syndrome and eating disorders. However, despite the wealth of data on differences, medical practice does not sufficiently take gender into account in diagnosis, treatment or disease management.

Also contributing to the disease gender gap is the medical research gender gap. Excluding women from clinical trials is negatively affecting women’s health. Today, even with mounting evidence of the gender differences in disease, women are still being ignored when it comes to health research. In a 2014 report, researchers at the Brigham and Women’s Hospital in Boston stated:

“The science that informs medicine – including the prevention, diagnosis and treatment of disease – routinely fails to consider the crucial impact of sex and gender. This happens in the earliest stages of research when females are excluded from animal and human studies or the sex of the animals isn’t stated in the published results. Once clinical trials begin, researchers frequently do not enroll adequate numbers of women or, when they do, fail to analyze or report data separately by sex. This hampers our ability to identify important differences that could benefit the health of all.”

Clinical trials designed to study the safety and effectiveness of drugs and other medical treatments are primarily done with men and historically women have been treated as “small men.” Even in diseases typical to women, generally the research is done with men. Can we apply what we learn from male rats or humans to a women’s physiology? No, we cannot. So why, even today, are men the primary test subjects in clinical trials?

The answer is both practical and political, without malicious intent. The practical reason is that men are easier to study because they do not have menstrual cycles and they do not get pregnant. As a result, research data are easier to analyze. The political reason for excluding women from clinical trials is also historical. In the 1950s, the drug thalidomide caused pregnant women to give birth to babies with missing limbs, and in the 1970s, DES, an estrogen-like drug prescribed to prevent miscarriages, increased the risk that female babies would develop rare vaginal cancers later in life. As a result, the Food and Drug Administration (FDA) in the United States banned all women who could become pregnant from participating in early-stage clinical trials. However, the ban ended up also including all women who were not sexually active, who used contraception or who were homosexual, as well as other minority groups. This law was upheld until 1993, even though in 1987 the National Institutes of Health (NIH) encouraged scientists seeking funding to include women and minorities in their clinical research.

Researchers surveyed papers published between 2011 and 2012 in five major surgical journals and found that in studies involving animals, 80 percent included only male subjects. In cell research, male cells were used 71 percent of the time, and in pre-clinical studies, the disparity was even more pronounced and skewed overwhelmingly male.

Millions of women and men are prescribed the same drugs every day, yet women are more likely than men to experience adverse drug reactions. In fact, 80 percent of prescription drugs pulled from the US market from 1997 to 2001 caused more side effects in women. Metabolic differences determine how drugs are released and excreted, leading to additional risk factors for women. Women are not just men with “boobs and tubes.” Lower body surface in women, as well as differences in kidney function, drug resorption and metabolism cause significant differences in how the body uses and excretes drugs. In addition, the gut transit time of medications, food or anything else women ingest takes two times longer than men and, as a result, these substances stay in the body for longer periods of time.

Major sex and gender differences have been reported for the efficacy and adverse effects of heart drugs, analgesics, psychiatric drugs, anticancer and cardiovascular drugs, as well as antidepressants, anti-inflammatory and antiviral drugs. These differences are related to the appropriate dosage for each gender. It would seem obvious, therefore, that many drugs require different dosing to achieve optimal effects. However, a 2005 analysis of 300 new drug applications between 1995 and 2000 found that even the drugs that showed substantial differences in how they were absorbed, metabolized and excreted by men and women had no sex-specific dosage recommendations on their labels. This might be one reason why women are 1.5–2 times more likely to develop an adverse reaction to prescription drugs than men.

In 1993, the US Congress passed an act requiring that all NIH-funded Phase 3 clinical trials include women, however the male-centric tendency still exists. According to a 2006 study in the Journal of Women’s Health, women made up less than one-quarter of all patients enrolled in 46 examined clinical trials completed in 2004. And although heart disease kills more women than all cancers combined, a 2008 study published in the Journal of the American College of Cardiology reported that women comprised only 10-47 percent of each subject pool in 19 heart-related clinical trials.

As a result, the question is if you are only studying males, how do you know the therapy will work or have the same effects or risk factors on women? Simple answer: You don’t! Dr. Jerilynn Prior, a professor of endocrinology at the University of British Columbia, says men are not adequate replacements for women in research. “It is not scientifically correct. Period. Full stop.” Women deserve to be studied to the same intensity and standards.

Many health care practitioners are not aware of the gender bias in clinical studies and the implications for women’s health. As a result, it becomes a bottom-up situation, requiring education of the public, and women in particular.

In health care, as in any area of life, it is crucial to understand what it is we are trying to achieve: the best level of health with the least degree of harm. Armed with a greater level of knowledge, a person is in a better position to more readily assess the ability of different medical approaches, based as they are on distinct philosophies, to meet individual needs. It also allows for greater participation in discussions with health care practitioners when making informed choices regarding health promotion and disease prevention, treatment and management.

It is always important to address the underlying causes of any condition when possible. There are times when treating symptoms of a disease with drugs or surgery is absolutely necessary, so it is important to be informed about the gender differences in treatment outcomes.

Medicine is both a science and an art. It is a science as it presents facts and evolves principles; it is an art as it applies these principles to suit the needs of individual patients. Practising the art of medicine requires active and careful listening. Unfortunately, we live in a world where studies and statistics take priority and many doctors have lost the art of listening to their patients. Gender remains an independent and important risk factor and sex and gender differences in common diseases must be considered in order to improve health and quality of health care for both women and men.

As an individual, you have choices: You can take the proactive approach by making health care choices that promote greater health and vitality and that are specifically intended to prevent disease from occurring. Should symptoms of disease strike, you can be prepared with a basic knowledge of what treatments are available to you which ones are the safest and most effective. Ask questions and learn to listen to your own body.

Karen JensenExcerpted from Women’s Health Matters: The influence of Gender on Disease by Dr. Karen Jensen, ND, www.mindpublishing.com

Karen Jensen received her degree in naturopathic medicine from the Canadian College of Naturopathic Medicine (CCNM) in 1988. She is a well-known author and lecturer.

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