Analyzing How Sex and Gender Interact

"Sex" and "gender" are distinguished for analytical purposes (see Sex and Gender). In reality, sex and gender interact (mutually shape one another) to form individual bodies, cognitive abilities, and disease patterns, etc. (Nowatzki & Grant, 2011; Fausto-Sterling, 2012; Schiebinger & Stefanick, 2020; Ritz & Greaves, 2022).

In brain research, for example, observed sex differences in biologic characteristics cannot be readily disentangled from social factors (Rippon et al., 2014). Gender norms shape dietary habits, physical activities, experience, and education—all of which are connected to brain functioning. Research, for instance, shows correlations between men’s higher education level in many countries and lower prevalence of Alzheimer’s disease in these countries (Schiebinger & Stefanick, 2020).

Today, some scholars use the term “sex/gender” to acknowledge that sex and gender interact (Kaiser, 2015; Hyde et al., 2018). The epidemiologist Nancy Krieger describes sex and gender interactions as the “biologic expressions of gender” and “gendered expressions of biology” (Krieger, 2001). Pain, for instance, is influenced by biological factors, such as sex differences in ischemic, thermal, pressure and muscle pain sensitivity (Bartley & Fillingim, 2013), and cultural aspects, such as differences in how women, men, and gender-diverse individuals report pain, how physicians treat pain in women and men patients, and how patients’ perceived level of pain sensitivity vary depending on the gender of the physician (Alabas et al., 2012; Chapman et al., 2018; Lepold et al., 2014—see also Case Study: Chronic Pain). Research also suggests that gender stereotypes about pain can change how much pain people are willing to report, and also how much pain they perceive (Schwarz et al., 2019).

Likewise, testosterone levels are associated with both biological factors (e.g., the circulation of sex steroids) and cultural ones (e.g., marital status in men; Holmboe et al., 2017). In places where cultural norms affirm fathers caring for their children, fathers have lower testosterone levels than in places where fathers typically provide little care (Fine, 2017). Moreover, some individuals use hormones like testosterone to change aspects of their bodies to better align with their gender identities.

Sex and Sex Interact
In animal research, interactions between the sexes can shape research outcomes. Consider, for instance, the longevity of the nematode C. elegans. Research demonstrates that the presence of male C. elegans accelerates aging and shortens the life span of individuals of the opposite sex, in this case hermaphrodites (Maures et al., 2014). Most lab-studies of animals examine females, males, and hermaphrodites separately. However, the sexes coexist in their natural environments, and ignoring interactions between them will restrict our knowledge of species viability (Tannenbaum et al., 2019).

Similarly, the sex of the experimenter conducting animal studies can moderate an animal’s response to treatment. For instance, research finds that mice are less prone to exhibit pain in the presence of a male experimenter compared to a female experimenter, and that this “male-observer effect” is larger in female than in male mice (Sorge et al., 2014—see Method: Analyzing Sex in Lab Animal Research). In this case, the animals don’t show pain when exposed to male pheromones. This phenomenon may throw into question all prior results from pain research.

Sex and Gender Interact
Sex and gender also interact to shape the ways we engineer and design objects, buildings, cities, and infrastructures. Recognizing how gender shapes sex and how sex influences culture is critical to designing quality research.

Example 1: How Sex and Gender interact when Exploring Markets for Assistive Technologies for the Elderly

new assistive technologies arrow

Example 2: How Sex and Gender Interact throughout the Life Course

factors influencing sex development from Regitz-Zagrosek, V. EMBOR 13 (7)

  • It is important to analyze the complex interdependency of sex and gender throughout the human life cycle (Regitz-Zagrosek, 2012). If we take health status, for example, sex influences health by modifying behavior. At the same time, gender behaviors can modify biological factors. Although women and men are fundamentally alike, differences of sex and gender can interact to produce differing health outcomes (see Heart Disease in Diverse Populations; Nutrigenomics; Osteoporosis Research in Men).

Example 3: How Sex and Gender Interact in Animal Research

blue rat sex and lab environment Interact
  • Animal research includes the interaction between sex (biological characteristics, such as genes, hormones, age, reproductive phase, strain, etc.) and cultural or environmental processes (such as caging practices, attitudes and behaviors of researchers, room temperature, diet, etc.). The double-ended arrows represent interactions between sex and lab environmental factors. Environmental processes, such as caging practices or differential handling (which may include gender assumptions and practices on the part of researchers), may impact male and female animals differently. Investigators should not identify an effect as dependent on sex (or a biological trait) when, in fact, it is influenced by an environmental (lab) condition (see Analyzing Sex in Lab Animal Research).

Example 4: How Sex, Gender, and other Factors Interact in Nutrigenomics

Cumulative Life Course risk factors for Non-communicable Disease (NCD)
  • Both sex- and gender-related factors determine an individual's functional capacity across the the course of their life. Because sex and gender interact, it is difficult to identify the respective influences of each factor independently. For a discussion, see Nutrigenomics.

Example 5: How Sex, Gender, and other Factors Interact in Pain

sex converges with gender to influence Pain
  • Pain has both biological aspects (sex differences in electrical, ischemic, thermal, pressure, and muscle pain sensitivity) and cultural aspects (gender factors in how people report pain and how physicians understand and treat pain in patients). What treatment a patient receives may depend on a patient’s gender and on a physician’s gender assumptions. Gender norms, for example, may influence a person’s willingness to report pain. These gender norms vary by ethnicity and other social factors. Physician gender assumptions may also influence treatments for women, men, and gender-diverse individuals. Clinicians often perceive women’s pain to be psychological; consequently, women may receive more non-specific diagnoses, wait longer for treatment, and receive more antidepressants and fewer painkillers than men—see Case Study: Chronic Pain.

Example 6: How Sex and Gender Interact in Systems Biology

sex and gender in systems biology

  • An individual’s biology is created and transformed by both their biological sex and their cultural gender identity and expression. To be maximally effective, fields such as precision medicine, pharmacotherapy, and nutrition must integrate both sex and gender as variables of analysis. Sex, which includes, e.g., chromosomal complement, circulating hormones, interacts with gender, which includes, e.g., cultural influences of ethnicity and social norms, in omics analysis, as illustrated in this diagram.

Works Cited

Alabas, O. A., Tashani, O. A., Tabasam, G., & Johnson, M. I. (2012). Gender role affects experimental pain responses: a systematic review with meta‐analysis. European Journal of Pain, 16, 1211–23.

Bartley, E. J., & Fillingim, R. B. (2013). Sex differences in pain: a brief review of clinical and experimental findings. British Journal of Anaesthesia, 111, 52–58.

Chapman, C. D., Benedict, C., & Schiöth, H. B. (2018). Experimenter gender and replicability in science. Science Advances, 4(1), doi: 10.1126/sciadv.1701427.

Fausto-Sterling, A. (2012). Sex/Gender: Biology in a Social World. New York: Routledge.

Fine, C. (2017). Testosterone Rex: Unmaking the Myths of Our Gendered Minds. London: Icon Books.

Holmboe, S. A., Priskorn, L., Jørgensen, N., Skakkebaek, N. E., Linneberg, A., Juul, A., & Andersson, A. M.  (2017). Influence of marital status on testosterone levels:a ten year follow-up of 1113 men. Psychoneuroendocrinology, 80, 155–161.

Hoffman, K. M., Trawalter, S., Axt, J. R., & Oliver, M. N. (2016). Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites. Proceedings of the National Academy of Sciences, 113(16), 4296-4301.

Kaiser, A. (2015). Re-conceptualizing “sex” and “gender” in the human brain. Zeitschrift für Psychologie, 220(2): 130-136.

Krieger, N. Genders, sexes, and health: what are the connections—and why does it matter? (2003). International Journal of Epidemiology, 32, 652–657.

Leopold, S., Beadling, L., Dobbs, M., Gebhardt, M., Lotke, P., Manner, P., Rimnac, C., & Wongworawat, M. (2014). Fairness to All: Gender and Sex in Scientific Reporting. Clinical Orthopaedics and Related Research, 472(2), 391-392.

Maures, T. J., Booth, L. N., Benayoun, B. A., Izrayelit, Y., Schroeder, F. C., & Brunet, A. (2014). Males shorten the life span of C. elegans hermaphrodites via secreted compounds. Science, 343(6170), 541-544.

Notwatski, N. & Grant, K. (2011). Sex is not Enough: The Need for Gender Based Analysis in Health Research. Health Care for Women International, 32 (4), 263-277.

Regitz-Zagrosek, V. (2012). Sex and Gender Differences in Health. European Molecular Biology Organization Reports, 13 (7), 596-603.

Ritz, S. A., & Greaves, L. (2022). Transcending the Male–Female Binary in Biomedical Research: Constellations, Heterogeneity, and Mechanism When Considering Sex and Gender. International Journal of Environmental Research and Public Health, 19(7), 4083.

Schiebinger, L. & Stefanick, M. (2020). Analyzing how sex and gender interact. Lancet (forthcoming).

Schwarz, K. A., Sprenger, C., Hidalgo, P., Pfister, R., Diekhof, E. K., & Buchel, C. (2019). How stereotypes affect pain. Scientific Reports, 9(1), 8626. doi:10.1038/s41598-019-45044-y

Sorge, R. E., Martin, L. J., Isbester, K. A., Sotocinal, S. G., Rosen, S., Tuttle, A. H., ... & Leger, P. (2014). Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nature methods, 11(6), 629.

Springer, K., Stellman, J., & Jordan-Young, R. (2012). Beyond a Category of Differences: A Theoretical Frame and Good Practice Guidelines for Researching Sex/Gender in Human Health. Social Science & Medicine, 74, 1817-1824.

Tannenbaum, C., Ellis, R., Eyssel, F., Zou, J., Schiebinger, L. (2019). Sex and gender analysis improves science and engineering. Nature, 575(7781), 137-146.

U.S. Food and Drug Administration (2014), Evaluation of Sex-Specific Data in Medical device Clinical Studies. Washington, D.C.



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