It’s fairly obvious to any middle-school level anatomy whiz why biological women develop cervical cancer, while their biological male counterparts are more prone to prostate cancer. But less obviously, why are females more prone to the development of lupus and other autoimmune diseases, while males present with significantly higher rates of overall infection? What about these biomedical nuances that exceed plain sight’s explanation?
The answer, plainly and simplistically, is hormones.
Our body’s tiny, but exceptionally powerful, chemical messengers – hormones have the power to alter mood, sleep cycles, muscle mass, and even organ development. The gonadocorticoids – commonly known as the sex hormones estrogen and androgen (testosterone) – play a fundamental role in initiating and maintaining the biological characteristics observed in each sex. Since the onset of modern biomedical research, hormones have been identified as the key to understanding the inner-workings of our highly complex physiological chain reactions.
In the case of injury and disease, then, why is it that scientists are terrified of these tiny tools? More specifically, they seem to be terrified of females.
Upon comparison, the hormonal profiles of males and females subjects look vastly different. Human male testosterone levels rise at a relatively constant rate until the age of 30, plateau, and then begin to decrease at the age of 70, forming a clean-cut, trapezoidal graph. On the other hand, for female subjects, picture a diagram of the roller-coaster variety. Estrogen and progesterone levels fluctuate continuously during the monthly menstrual cycle of a female’s reproductive years; moreover, the levels of these hormones can vary exponentially before puberty and after menopause. In the modern era, the profiles of human females are diversified further by the widespread use of hormonal contraceptives, such as birth control pills and intrauterine devices.
This hormonal variability has time and time again been cited as reason for female exclusion in human and animal studies alike. Where endocrinologists see flow charts, biomedical researchers see unnecessary complications and confounders in their subject pool – the females have simply been deemed too complicated to analyze.
The field of neurotrauma is among the most pressing of these case studies in inequity. The failure of the scientific community to employ sex-equitable techniques in the realm of Traumatic Brain Injury (TBI) research has resulted in tangiblely unjust consequences for patients in the Emergency Room and beyond. Inequity is a disease that has plagued the medical community’s past and present research endeavors, undermining the care quality of millions of patients. There is an increasing urgency in the need for comprehensive, sex-stratified research in order to fully rebuild this trust and provide competent patient care.
TBI is among the leading causes of death and disability for adults in the United States, affecting upwards of 2.5 million patients annually. Though Traumatic Brain Injury has long since been a pathology of study in the medical community, evidence points to unexplained and unexamined discrepancies: time and time again, while the male patients seem to recover, the females do not.
As exemplified by a 2021 clinical data review of over 4,000 charts of moderate to severe TBI patients, female victims have a disproportionately higher mortality rate, in addition to an increased risk for post-injury psychosocial symptoms. Female patients report significantly elevated levels of depression, anxiety, post-traumatic stress, and overall poorer global outcomes when measured against their demographically comparable male counterparts.
Although men, women, and nonbinary folks alike have heads on their shoulders, why is it that TBI, like countless other medical diagnoses, affects them in vastly different manners? The medical community cannot answer this question, but the bigger problem is that they haven’t tried to.
The current literature clearly demonstrates that females have been underrepresented in clinical trials of TBI and have often been excluded in preclinical animal studies, as well. Though historically considered to be a male-dominated injury, rates of female patients affected by TBI have risen significantly in recent decades due to increased participation in athletics, military service, and reporting of interpersonal violence. In the face of this highly documented demographic shift, the medical community has failed to react, remaining paralyzed in their old ways of the “one size fits all” male standard patient model.
In an attempt to heal the sex-segregated chasm forming between standards of research quality, the National Institute of Health issued the 1993 Revitalization Act PL 103-43. This long overdue piece of legislation established national guidelines for the inclusion of women and minorities in clinical research opportunities as a requirement for funding eligibility. The NIH’s guidelines were a step in the right direction towards closing a miles-wide gap in health equity; however, it remains imperative to recognize that one well-intended guideline is not enough to erase science’s ugly history.
An analysis of major neuroscience publications between 2009 and 2019 revealed an over 30% increase in the number of studies including both sexes in their subject pools. Despite this apparent jump in inclusion, merely 19% of these experiments actually analyzed sex-specific data in a meaningful way. This is the scientific equivalent to a designer determining the average body size of all human beings everywhere, and only making clothes for that single model. Although efficient, this method is undeniably ignorant, impractical, and unjust.
In neuroscience and beyond, the scientific community does not need to treat men and women as one equal entity, but instead must see them as distinct groups to be studied in their full complexity. We need researchers willing to put in the time and care to study their subjects with respect to hormonal data. We need clinical laboratories to take on prepubescent, postmenopausal, and hormonally-supplemented people in their studies. We need more teams to dedicate themselves to the study of sex-hormones as their primary variable of interest, rather than simply a side task. We need clothes that fit all people, of all sizes.
Only then can the institution of medicine do justice to the biological nuances of the people it is meant to serve. Clinicians and researchers alike must recognize that true inclusion means honoring and paying attention to differences, rather than enacting a one-size-fits all policy on groups that have historically been ignored by such metrics.