Women in Health & Biomedical Research: What You Should Know & Why It Matters

Cherise Charleswell

Many have made the argument that “Women’s diseases are not better understood or well researched simply due to the fact that they are women’s diseases”. An example of this would be the limited scientific knowledge around pre-eclampsia, a pregnancy complication that impacts 5-7% of all births in the United States and up to 18% in countries is the Global South, which has no reliable method for early detection, or real treatment. Mother’s simply have to carry their growing fetus to term and “see what happens.” And to clarify, the statistic speaks to the number of births, and not necessarily the number of mother’s who have the condition. Thus, any given women having more than one pregnancy can find themselves having this complication more than once. Research Scientist who focus on the field of gynecological immunology, and who have studies focused on pregnancy complications such as pre-eclampsia, often lament that there is at times not enough interest or excitement about their research in the scientific community, and it can be discouraging.

In other words, the value system of dominant patriarchal societies do not place much concern over the health and well-being of women. Social scientists would surely echo this notion, when considering their work around describing the phenomenon that is referred to as the “Feminization of Poverty“. The truth of the matter is that this phenomenon is also connected to this problem of disparity when it comes to women’s health and biomedical research. Further, when addressing this problem, the concern should not only be on diseases that are women’s diseases – or those that solely impact women, such as uterine cancer, but also on other diseases, disorders, etc. that are likely to affect all human beings, regardless of gender, such as diabetes.

Actually what has been taking place with women’s health and biomedical research can only be accurately described as an inequity; meaning that the differences in representation, access, and health outcomes are unjust, unfair, and should be prevented. When it comes to inclusion in research studies and clinical trials, the idea of “fairness” is reflective of distributive justice, where members of a society should rightfully get their fair share of its burdens and benefits. That is to say that despite the risks of burdens, there is a great chance to benefit from taking part in these studies, and women deserve a fair chance in receiving these benefits.
So What Are the Reasons Behind The Disparities?

There is no debate about the existence of the disparities in representation and access for women to health and biomedical research. A 2011 report jointly put out by The Society for Women’s Health Research and the U.S. Federal Drug Administration Office on Women’s Health found that, for cardiovascular diseases that are prevalent in the United States, the sex distribution for cardiovascular device trials (such as pacemakers) were 67% male . However, even among researchers the causes for these disparities are not well understood and discussed.
Women as a Vulnerable Population

Pregnant women are among a distinctive group of research participants that are deemed vulnerable populations. The need for specific legislation and the desire to protect the growing fetus is understandable. However, setting policies that are too stringent and make it hard to learn more about pregnant women’s bodies, abnormalities, and disorders, results in them not being able to have improved and more effective health services. In the case of preeclampsia, a better understanding of the “behavior” of a women’s T lymphocyte cells (which when functioning properly allow the mother to accept the growing fetus, which should be viewed as a foreign body, particularly in that it has 50% genetic contribution from the father) will allow for earlier detection of the condition. This early detection will allow for proactive forms of treatment, which will modify the behavior of T cells to make them more tolerable.
Menopause & Menstruation

When it comes to the inclusion of women in biomedical research studies, often times not enough consideration is given to the complexity of a women’s life cycle, and how our bodies may present differently at varying stages. These gender-based polymorphisms may impact how we process information, metabolize drugs, feel temperature (hot flashes in menopausal women), or even pain (breast tenderness in menstruating women). Yet, there are no concerted efforts to analyze populations of women based on age and reproductive cycle; and this includes noting whether they are being examined during menopause or during menstruation. Previous research has already shown that women do indeed exhibit polymorphism during different stages of the menstrual cycle as well as pre-and-postmenopuase (Mastrioanni et al, pp 140-I).
Socioeconomic Barriers

The feminization of poverty directly impacts women’s ability to access health and biomedical research studies; particularly women of color. The fact that women are typically primary caregivers and many head single-parent homes, along with the fact that women continue to earn less than men in the USand globally is a lethal combination. It means that women will be less likely to afford transportation to get to a clinician, or have a well-paying job with the benefit of insurance, or the money to see a physician; which is how one is most likely to get referred to a clinical study. These socioeconomic barriers also include: a woman (especially a mother who has to be careful with her sick days or a low-wage work that does not get paid time off) being unable to take time off of work to make it to appointments, then there is the time and cost investment in commuting to the research appointments-for which a number of studies do not reimburse. Insurance sometimes becomes another issue once a subject is enrolled, because studies do not again cover all necessary tests; such as blood draws.
Social Bias

Sexism which leads to social bias is another clear and present barrier for women’s involvement in health and biomedical research. Essentially what occurs is that clinicians and researchers look at women as if they are child-like, emotional, and too rational to trust their complaints regarding health issues. Thus, they are either misdiagnosed or simply dismissed; as if they were merely crying wolf. A direct result of these sexism beliefs has been that women are more hesitant to seek health services, or be forthright about the symptoms that they may be experiencing. In other words they do not want to “bitch” or “nag”. A recently released 2015 study suggests that younger women who may have heart attacks may actually hesitate to get help because they’re afraid of being labeled hypochondriacs, and this is of course despite the fact that women are twice as likely to die of a heart attack than their male counterparts. The 2015 Yale School of Public Health Study, titled Symptom Recognition and Healthcare Experiences of Young Women With Acute Myocardial Infarction, results used terminology such as “ignore” and “dismiss” to describe how women’s comments about the symptoms were received; and “hesitate” or “delay” to describe women’s health seeking behavior.

Another example of a result of this bias are significant sex and race disparities that are found in rates of numerous medical procedures, even there are equivalent levels of access to care (National Academics Institute of Medicine, 2002; Vaccarino et al., 2005). Therefore, while heart disease remains the leading cause of death for both women and men in the United States, and the number of women and men hospitalized with cardiovascular disease is similar; the rates of bypass surgery among women and minorities are far below bypass rates among White men (Travis, 2005). Thus, it is white men who get the benefit of access to care, including cutting edge research technologies that can help to improve surgical outcomes and prolong life. Another example is the article, Perceived sexism as a health determinant in Spain, published in 2010 in the Journal of Women’s Health, which shared the results of a study, whose objectives was to explore the association between perceived sexism and self-perceived health, health-related behaviors, and unmet medical care needs among women in Spain (Borrell et al. 2010). They were ultimately trying to identify whether discrimination was associated with a higher prevalence of poor health indicators; and what they found was that there was a consistent association between perceived sexism and poor health outcomes in Spain, a country with a strong patriarchal tradition (Borrell et al., 2010).

Sexism and social bias has also resulted in physicians and researchers being relatively ignorant about how a number of diseases impact women and their overall prevalence. An example of this is again heart disease. Although more women than men have died each year from cardiovascular-related causes since 1984, according to a 2005 study, fewer than one in five doctors – which included primary care physicians, obstetricians/gynecologist, and even cardiologists-were aware of this. That outcome of this bias again, is that women are not readily treated or provided with surgical care, they are not referred out to research and clinical studies, they are not given an opportunity to equally benefit from the innovative research, and they ultimately will have higher rates of mortality than men (and this may also be due to the fact that the available therapies were again only researched on an overwhelmingly male cohort and may not be applicable or nearly as affected in women).
Cultural Barriers & Restrictions

Cultural beliefs and practices in extremely patriarchal societies present the greatest danger to women’s involvement in health and biomedical research. These are the societies where women have extremely limited access to medical care for various reasons, such as a social mandate that they cannot be seen by a male physician, and restrictions on access to education that decrease the number of available female physicians; who would be allowed to care for these patients. Even when traveling outside of these societies, or countries, these women remain under the yoke of their cultural heritage; and are still unable to access care and are thus unlikely to have the opportunity to engage in and benefit from biomedical research. Examples of this double-barrier are well published, including the cases in Burundiand Saudi Arabia.
Lack of Women in STEM

The lack of women in STEM (Science, Technology, Engineering, and Math) fields also adds to this disparity of women participants in health and biomedical research, particularly women of color, who come from communities that have a long-standing history of distrust of the biomedical research field.

This barrier is carried out in principally (3 ) ways: First, the lack of representation of women in the STEM work field may translate into a lack of considerations of the needs of women and the complexities of their bodies, which may impact study results. Second, this disparity is will reduce the likelihood that women will feel comfortable enough to participate in these studies. There is much to be said for relatability; and in extreme cases access to women doctors and researchers is critical to women and girls being allowed to be treated and receive care. Also, a higher rate of women clinicians could help to mitigate the problem of women not being referred to studies due to sexist beliefs and provider bias. Next, the lack of women in STEM in positions of power means that they do not have much of a voice on boards and review committees that control budgets and decide which studies are worthy of funding.

There has been much discussion around the lack of representation of women in STEM, and those discussions are expanding to include not only the difficulty in recruiting women to the field, but the obstacles to ensuring retention. The problem was initially viewed as a mere problem of interest, one that can be solved by getting girls and women interested and excited about science; and of course no consideration was giving to the “culture of STEM”, where male dominance and larger numbers have helped to created situations that resemble the “Good Ol’ Boys Network”. Again, the underlying problem is sexism. For example, a 2012 randomized, double-blind study presented science faculty at research-intensive universities the application materials of a fictitious student. They randomly assigned a male or female name to the student; and the results were that both male and female faculty rated the male applicant as significantly more competent and hirable than the woman with identical application materials. Evidently women can be just as sexist as men, when it comes to what has been ingrained in them socially.

A separate 2014 study found that both men and women were twice as likely to hire a man for a job that required math. Thus, the picture as to why there is a lack of women working in STEM should begin to become clearer. Recently a team of women researchers conducted a study, carrying out 60 in-depth interviews with 60 female scientists and surveyed a 557 female scientists, in order to get a better understanding of the issue of gender bias in STEM. They uncovered a number of barriers and learned about the type of microagressions that women in STEM faced. The following infographic shows some of the results of that study.

Essentially, the study uncovered that there were distinctive patterns to the biases that women experienced; and that women of color experienced them in different ways. The following is an overview of those patterns:

Pattern

Description of The Bias

Those Most Impacted

Patten1 : Prove It Again 2/3 of women respondents reported having to prove themselves over-and-over again; their successes were discounted and their expertise questioned. Black women were considerably more likely than other women to report having this bias. ¾ of Black women reported this bias.
Pattern 2: The Tightrope Occurs when women find that they have to behave in a masculine way in order to be seen a competent; and compete in the field, all while having to deal with the expectation that they be feminine.

34.1% of the scientist surveyed reported feeling pressured to play a traditionally feminine role.

53.0% of scientists reported backlash for being perceived as too “masculine”-speaking their minds directly or being decisive.

40.9% of Asian American women reported this bias; and this may have much to do with the stereotype of the docile and submissive Asian woman.

Latina and Black women also reported being at risk for being perceived as angry. Black respondents felt that they really had to restrain themselves, so that they would not trigger the “angry Black woman” stereotype. Of course this restraint and unwillingness to provide input makes one look incompetent.

Pattern 3: The Maternal Wall Once a woman becomes a mother they quickly find that their commitment and competence are questioned.

Nearly 2/3 of the responding scientists with children reported running into this form of bias, which came with a loss of opportunities. After all they were competing with many male colleagues who had stay-at-home wives, who are perceived as being more available.

This bias was seen across all races and ethnic groups.
Pattern 4: Tug-of-War An unfortunate result of women encountering discrimination early in their careers is that they distance themselves from other women; and with this distance goes many opportunities for mentorship, etc.

¾ of the women scientists surveyed reported that women in their work environment supported each other; yet 1/5 reported that they feel like they were directly competing with female colleagues for the “woman spot”. In other words, competing to be the token.

This bias was seen across all races and ethnic groups
Part 5: Isolation 42% of Black women felt as if socially engaging with colleagues may negatively affect perceptions of their competence. Similar responses were given by 38% of Latinas, 37% of Asian Americans, and 32% of white women. Applies mainly to Black and Latina women.

As bleak as the reports of bias for women in general seem, the problem is more pronounced for women of color; who have to cope with the intersectional reality of being both women and a racial/ethnic minority in the STEM fields that are dominated by white men. In my own case, a situation that stands out, is I walked into an Executive Board planning meeting, right as a colleague was discussing his genetic theory behind Black people’s love of dance and music; based on his observations of lesser primates. There are other times when my hair seems to be a topic that is far more interested than the research being conducting, and I am asked about or referred to as Angela Davis; oh there are really too many examples to continue to list.

The 2015 report conducted by the University of California’s Hastings College of Law found that 100% of the women of color interviewed experienced gender bias; and amount that was slightly higher than 93% of white women respondents. With these odds the bottom line is as such- there is no denying gender bias in STEM, and if you are a women of color, you will definitely experience it. As found by other studies women of color dealt with more than just sexist views, but had to also cope with unwarranted stereotypes.

The male-dominated STEM fields are also plagued by issues of sexual harassment. As one colleague once stated to me, “It is tough, forget about What would you do for a Klondike bar, and ask What would you do to get your name further up the list of contributing authors, or approved for a fellowship? Those in control of these decisions are just about all men.” And the Hastings report reflects these sentiments. One-third of the women surveyed experienced sexual harassment. While other studies have found that women of color were more likely to be harassed (due to perceived vulnerability and racial sexual stereotypes); the respondents to this study who were more likely to experience sexual harassment were White women (37.2%), compared to 25% Asian Americans, 21.9% Latinas, and 12.5% of Black women.

To truly get an understanding of how sexist the STEM field may be, one should just consider a storythat broke on April 30, 2015, where two female researchers who submitted their manuscript for peer review – a process by which scientists uninvolved in a study evaluates its merits and decides whether it is fit to publish – received a single review for their rejected manuscript, which stated that the mere act of brining in some men on their team might fix all of the problems. The assumption was made that men were more critical, objective, and perhaps even knowledgeable scientists. So, we should disregard people like Marie Curie and her daughter Irène Joliot-Curie,Rita Levi-Montalcini, Mae Jemison, and so many more. The offending journal was part of the PLos family; and the specific “suggestions” given included:

Ultimately even when there is success in filling the pipeline and recruiting women to STEM, one has to consider the issue of retention; to counteract women leaving the field, because they find it incredibly unpleasant and oppressive.
Ethical Considerations

So, why the fuss? Why should there be such a great concern over the low rates of women’s participation in health and biomedical research? To answer this question — once must provide an ethical explanation that is based on the physiological differences between the bodies of women and men. The short response would be that, because the two sexes are not the same, they vary in size, genetics (X and Y chromosome), anatomy (particularly the reproductive system), as well as bodily functions such as metabolism. Thus, any therapeutic, device, or intervention that is approved or will be used to treat women; should first be tested, reviewed, and analyzed to ensure that it is indeed applicable to a woman’s body and won’t cause unforeseen harm.

So, let’s consider what these ethical concerns more closely. What could be problematic about the following:

  • A 2007 review of the American Heart Disease Association’s prevention guidelines for women, which drew on studies in which women only made up only 30% of the subject population; further only 1/3 of the studies even bothered to break down the results by gender.

· The fact that heart attacks in women are less likely to adhere to the textbook model.

· Medical devices are subject to gender bias, and are typically designed for men, due to the overrepresentation of men in device trials. In fact the FDA has been criticized for gender bias in premarket approval of cardiovascular devices, where 67% of the participants were male (Dhruva et al, 2011). All this despite the fact that women have a higher prevalence of cardiovascular diseases.

o The problem: This gender bias puts women at great risk, which can be life threatening. Devices can dislodge, provide too great of a dosage of medication or electrical current, etc.

1. Examples of this incompatibility include the first generation of the HeartMate II Ventricular Assistance Device, which could not be used in women, because a woman’s heart/chest was simply too small to accommodate the device.

2. With women having a different angulation of hip than men, which results in more rapid wearing down of male-centric surgical implants; and resulting in differences in outcomes in terms of pain and mobility.

· Or even the fact that cars are typically designed for the average woman, with automakers only being required in law, after 2011 to use female crash-test dummies. (Newcomb, 2012).

o The problem: Men and women sitting in the same car crash are likely to suffer different injuries; including an elevate risk of traumatic brain injury in women (Shifflet, 2014). Seatbelts that are typically placed too high for the average women, results to them sustaining cut into their necks during collisions.

· In providing and studying a course of treatment in women, the menstrual cycle is rarely considered during clinical research studies.

o The problem: The menstrual cycle can affect pain response, drug addiction, withdrawal, and even brain injury. In fact, the point in a woman’s cycle when her injury occurs impacts both severity and rate of healing (Wunderle, 2013).

· The conduct of drug trials with little to no participants who are women; or the conduct of a drug trial where gender/sex differences are not considered or assessed during data analysis.

o The problem: There are sex-related differences in pharmacokinetics and pharmodynamics; which essentially look at the relationship of drug dosage and concentration of the drug in the blood, cells, and tissue over time.

1. Gastric emptying time is slower in women than men, primarily due to the effects of estrogen (Gandhi, 2004). Further, drug excretion is mediated by the kidneys or liver through what is referred to as Glomerular filtration. Glomerular filtration, which is directly proportional to weight, is higher on average in men than women (Schwartz, 2003). Thus, consideration needs to be taken when figuring out appropriate drug dosage. The fact that it takes women much longer to eliminate drugs, means that in some drugs they may require less dosages than men. In other words, sex-adjusted dosages are needed and need to be determined during a drugs clinical trials. 8 of the last 10 drugs withdrawn from the market posed a greater health risk to women (Gen Accounting Office, 2001).

In the end the problem is that they inherent differences in the physiology of men and women may cause them to respond to a therapeutic, device, and intervention differently, and these differences must be consider by all those who are conducting health and biomedical research studies. Inclusion of women in clinical trials, health and biomedical research studies must be increased to obtain critical sex-specific data. In fact, the important measure of success of any clinical or medical device trial should be on whether there is a generability of study findings; and an applicability of results to the varying different populations – women, racial and ethnic minorities, etc. – who will be using the produce, procedure, device, or intervention.
Strategies to Overcome the Disparity

There are a number of strategies that are currently being employed or considered to reduce this disparity of women’s participation in health and biomedical research; which leaves them at a great disadvantage in terms of benefits and improved health outcomes, while putting them at risk for adverse events and higher rate of mortality. These strategies include federal legislation and policies, changes in institutional policies, advocacy and outreach, as well as efforts to build a pipeline for women in STEM; of course these efforts must include plans for retention considering the hostile environment that these fields can be for women.
Legislation

The following is a list of federal legislation that relate to women in clinical research:

Other policies include:

2005 – The Food and Drug Administration outlines its own guidance recommendations to industry for a standardized approach to the collection of race and ethnicity data. The guidelines required the following: clinical findings must now be reported by sex, race and age. However, there still remained no requirement for inclusion of women and/or minorities in industry-sponsored clinical trials.

Section 907 of the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) directs the FDA to publish and provide a report to Congress that “addresses the extent to which clinical trial participation and the inclusion of safety and effectiveness data by demographic subgroups, including sex, age, race, and ethnicity, is included in applications submitted to the Food and Drug Administration (FDA, 2012).

In 2014 the National Institutes of Health announced a new transition plan for reporting sex/gender race, and ethnicity information. The transition included the modification of forms used to provide information regarding planned enrollment and actual cumulative enrollment of individuals involved in clinical research studies by sex/gender, race, and ethnicity. The “actual cumulative enrollment” part is quite important, because it increases the likelihood that researchers will actually do as they state in their planned enrollment templates, and recruit a diverse cohort of participants; simply because they will be held accountable. Also, announced was the new Inclusion Management System (IMS), which applicants and grantees will have to use. The system released in October 2014, allows for end-users to directly manage their inclusion data; and again requires reporting of sex/gender race, and ethnicity information.
Building the Pipeline

Building the pipeline and getting women more interested in STEM and increasing their numbers in the workforce is essential, because their presence and visibility serves as a way to recruit more women participants. Again, there is much to say about relatability, comfort, and trust. Further having more women in STEM will possibly increase the likelihood that diseases that affect women will be given more attention, more funding, and will be better studied; along with an increase in data collection and analysis that looks at sex-related differences. However, efforts should not just focus on building the pipeline, but on improving the workplace environment for women in STEM, in order to bolster retention. This will require a commitment from Institutions; such as diversity and sensitivity training of researchers, addressing sexual harassment and sexism, improved mentorship programs, increasing the number of women in leadership positions (yes-set some quotas if needed!) and creating environments where women do not have to worry about whether their input and /or behavior will be judged according to stereotypes.
Advocacy & Awareness

Bottom line – there are going to be more direct appeals to the public; particularly women and educational outreach efforts. Many women truly do not know about research opportunities and why they are so important. Instead, they readily pop a pill or get a medical device implanted, and do not realize that there may be a risk in doing so, because these items were likely not developed with them in mind. Increasing awareness may lead them to seek out these studies and gain access to cutting-edge therapeutics and interventions; and to be more forthcoming when inquiring about what is available when meeting with their doctors. Also, doctors must be made more aware of these sex-related differences, their own biases, and the critical need to increase women’s participation in research.
Removing Socioeconomic Barriers

Addressing these barriers will not be easy, unless one has a magic wand that can remove the intersectional issues of race, sex, and class that marginalizes certain groups, and make them more susceptible to economic uncertainty. Those conducting research studies should simply be mindful of these barriers, and thus flexible with their overall study design and protocols. For instance, the cost of transport to the research facilities, can be mitigated by budgeting for this cost to participants in a grant proposal. Create a separate line item. Also, consider that many women, particularly low-wage workers do not have that much available time; and may not receive paid time off from work; and even if they did, they would want to reserve those days for when there is an absolute necessity, such as dealing with illness. Thus, appointment times should be flexible, and that includes having weekend availability. Researchers should consider covering all medical costs related to their study, for example, participants should not have to pay for consecutive blood draws and lab analysis. If a research study cannot do this work in-house, they should contract out with a provider and again budget for this cost up-front.

Ultimately it is critical that we ensure that health and biomedical research studies are equitable, and that the number of women in these studies increase. Doing so is a matter of health equity that ensures that women, who again represent half of the taxpayers that fund these studies, share an equal opportunity to benefit from them. Also, to reduce adverse events, risks, and safeguard the health of women-who will be the end users of the therapeutics, devices, and interventions that are developed from these studies.

References

Carme Borrell, Lucia Artazcoz, Diana Gil-González, Glòria Pérez, Izabella Rohlfs, and Katherine Pérez. Journal of Women’s Health. April 2010, 19(4): 741-750. doi:10.1089/jwh.2009.1594.

Dhruva SS, et al. (2011). Gender bias in studies for Food and Drug Administration premarket approval of cardiovascular devices. Circulation: Cardiovascular Quality and Outcomes. 4(2):165-171.

Food and Drug Administration Safety and Innovation Act of 2012, P.L. 112-144, July 9, 2012.

Gandhi M, Aweeka F, Greenblatt RM, Blashcke TF. (2004). Sex differences in pharmacodynamics of drugs. Annu Rev Pharmacol Toxicology. 44:499-523.

General Accounting Office. (2001). Drugs withdrawn from market. (GAO-01-286R). Washington DC.

Mastrioanni A, Fraden R, Federman D, eds. Women and health research. Washington: National Academy Press, 1994.

National Academies Institute of Medicine. (2002). Unequal treatment: What healthcare

providers need to know about racial and ethnic disparities in health-care. Washington,

DC: National Academy Press

Newcomb D. (2012 Aug 30). Why it took decades for a female crash test dummy to debut: Automakers for years fought to use only crash dummies modeled after the average American male”. Exhaust Notes. Editorial.

Schwartz JB. (2003). The influence of sex on pharmacokinetics. Clin Pharmacokinetics. 42(2):107-121.

Travis, C. B. (2005). 2004 Carolyn Sherif award address: Heart disease and gender inequity.

Psychology of Women Quarterly, 29(1), 15-23. doi: 10.1111/j.1471-6402.2005.00163.x

Vaccarino, V., Rathore, S. S., Wenger, N. K., Frederick, P. D., Abramson, J. L., Barron, H. V., et

al. (2005). Sex and racial differences in the management of acute myocardial infarction,

71 1994 through 2002. New England Journal of Medicine, 353, 671-682. doi:

10.1056/NEJMsa032214

Wunderele K, Hoeger KM, Wasserman E et al, (2013). Menstural phase as predictor of outcome after mild traumatic brain injury in women. Joural of Head Trauma Rehabilitation. PMID: 24220566.

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