Sex & Gender Matter!

COMMENTARY

By: Reema Shafi

While used interchangeably, sex and gender are two distinct concepts. Both have implications for human behaviour and health. Sex refers to the biological differences (genes, anatomy, hormones) human beings have at birth, while gender alludes to the social (behaviour, identity) and cultural (norms, roles) differences that exist as a result of our experiences as societal beings (1, 2). These biological and social/cultural factors impact our disposition to medical conditions and compliance to treatment.

Until recently, basic science research has been strongly sex-biased given the exclusive use of male rats for pre-clinical trials (3). Sex and gender have also been poorly integrated in health services research and hence the impact on health and rehabilitation has mostly been overlooked. While most research designs include sex as a demographic factor, a recent systematic review (4) revealed that only 7% of studies that looked at outcomes after traumatic brain injury actually reported on potential sex differences. Yet, there is some evidence to support that females have poorer outcomes following brain injury (5,6).

Irrespective of the scarcity of sex- and gender-based health research, we know that many neurological conditions are ‘sex’-biased. That is, there are known differences that exist between males and females in prevalence, onset, symptomatology and outcome. For instance, the Centre for Disease Control and Prevention reports depression to be much more prevalent in females, while autism is more common in males .

Sex differences at the neural level, in regional tissue volume and density, are well documented. Males, on average, have larger amygdale and thalamic volumes, while in comparison females have larger hippocampal volumes (7). When comparing on cognitive-behavioural measures, males perform better on spatial memory tasks and females on verbal memory (8,9). With respect to structural connectivity, males show greater intra-hemispheric cortical connectivity while females have higher inter-hemispheric connectivity (10), perhaps suggesting varied patterns of processing. Through the aging process, females have greater hippocampal and parietal atrophic losses compared to males (11). Atrophic changes though begin earlier for males, but the rate of atrophy is more rapid for females (12). Estrogen modulates specific aspects of cognition (13) and females have a higher number of estrogen receptors in the hippocampus (14). One possible explanation for this rapid atrophy could be attributed to low circulating levels of estrogen in post-menopausal women. The fact that the prevalence rate of dementia is equal across sexes at age 60, but then increases by 57% in females by age 85 triangulates well with our current understanding of neuropathophysiology.

So, is it merely a string of biological mechanisms that sets males and females apart, or are other factors also at play?

Apart from our biological orientation, societal ‘influences’ play a pivotal role in shaping us as beings. A common example is societal pressures which encouraging girls towards nurturing and boys as bread-earners. We learn from these experiences. Learning modifies behaviour. Behaviours lead to patterns of action (i.e. lifestyle choices, diet, risky sports), with consequences that impact health and well-being. These subtle yet critical influences shape us as gendered beings. They impact how we make decisions regarding health care, which can dictate our chances of recovery or influence the extent of benefit we gain from an intervention.

If the societal influences are diverse then health outcomes are bound to vary. Women from diverse parts of the world may respond differently to a similar health concern. An urban working female living in a developed country may consider preventative measures and seek treatment for osteoporosis. In contrast, a rural female homemaker living in a remote village of a developing country may be limited due to health education or access to care. The subsequent healthcare decisions undertaken are influenced by factors beyond their biological orientation.

Advances in neuroscience have demonstrated that male and female brains are “hard-wired” differently. Our bodies maintain and adjust to a careful balance of sex-specific hormonal cocktails that influence our biology. Our unique societal ‘influences’ shape us further into diverse gendered beings, yet we so commonly fail to consider and acknowledge the impact of these factors when conducting health and rehabilitation research.

Within the context of rehabilitation science we seek to understand the mechanisms of health and recovery. To do this, we need to better understand the unique and accumulative contributions sex and gender have on health. Irrespective of the object of our study (cells, humans, animals), the integration of sex and gender in our methodology will translate into a non-biased scientific inquiry that can help improve outcomes globally.


References

  1. Canadian Institutes of Health Research–Institute of Gender and Health. (2015). Retrieved from http://www.cihr-irsc.gc.ca/e/47830.html.
  2. World Health Organization. (n.d.). Retrieved from http://apps.who.int/gender/whatisgender/en/.
  3. Beery AK, Zucker I. Sex Bias in Neuroscience and Biomedical Research. Neuroscience and Biobehavioral Reviews. 2011;35(3):565–572.
  4. Cancelliere C, Donovan J,  Cassidy D. Is Sex an Indicator of Prognosis After Mild Traumatic Brain Injury: A Systematic Analysis of the Findings of the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury and the International Collaboration on Mild Traumatic Brain Injury Prognosis. Archives of Physical Medicine and Rehabilitation. 2016;97(2): S5-S18.
  5. Colantonio A, Mar W, Escobar M, Yoshida K, Velikonja D, Rizoli S, Cusimano M, Cullen N. Women’s Health Outcomes After Traumatic Brain Injury. Journal of Women’s Health. 2010;19(6):1109-1116.
  6. Bazarian JJ, Blyth B, Mookerjee S, He H, Mcdermott MP. Sex Differences in Outcome after Mild Traumatic Brain Injury. Journal of Neurotrauma. 2010; 27(3):527-539.
  7. Koolschijn PCMP, Crone EA. Sex differences and structural brain maturation from childhood to early adulthood. Developmental Cognitive Neuroscience. 2013;5:106-118.
  8. Jansen P, Kaltner S. Object-based and egocentric mental rotation performance in older adults: the importance of gender differences and motor ability. Aging, Neuropsychology, and Cognition. 2014;21(3):296–316.
  9. Heinzel S, Metzger FG, Ehlis A, Korell R, Alboji A, Haeussinger FB, Hagen K, Maetzler W, Eschweiler GW, Berg D, Fallgatter AJ, the TREND Study Consortium. Aging-related cortical reorganization of verbal fluency processing: a functional near-infrared spectroscopy study. Neurobiology of Aging. 2013;34(2):439-450.
  10. Ingalhalikar M, Smith A, Parker D, Satterthwaite TD, Elliott MA, Ruparel K, Verma R. .Sex differences in the structural connectome of the human brain. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(2): 823–828.
  11. Murphy DG, DeCarli C, McIntosh AR, Daly E, Mentis MJ, Pietrini P, Szczepanik J, Schapiro MB, Grady CL, Horwitz B, Rapoport SI. Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging. Arch. Genet. Psychiatry. 1996;53:585–594.
  12. Takeda S, Matsuzawa T. Age-related brain atrophy: a study with computed tomography. J. Gerentol. 1985;40:159–163.
  13. Phillips SM,  Sherwin BB. Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology. 1992;17:485–495.
  14. Morse JK, Scheff SW, DeKosky ST. Gonadal steroids influence axon sprouting in the hippocampal dentate gyrus: a sexually dimorphic response. Exp. Neurol. 1986; 94:649–658.