Let's talk about sex as a biological variable

Funding agencies across the globe are pushing for sex to be considered as a biological variable in all stages of the research they fund, from study design to data analysis and reporting. Likewise, an increasing number of journals require that sex aspects be addressed in the papers they publish. Here, three KI researchers share their experience of integrating sex as a biological variable (SABV) in their own work and explain how doing so benefits their research.

Christopher Cederroth: tinnitus research

Christopher Cederroth's lab seeks to uncover the mechanisms underlying tinnitus, the ringing in the ears or phantom perception of sounds. Through studies in animal models and on humans, they have shown that the pathophysiology of tinnitus is sexually dimorphic. They found that the heritability of tinnitus is greater in men than in women, but that women experience greater levels of stress, anxiety, and hyperacusis (sensitivity to sounds) in response to constant tinnitus. Moreover, tinnitus increases the risk of suicidal attempts in women but not in men.

"In [a] recent article we have published revealing sex-dependent influences of tinnitus on suicide attempt, such dimorphic aspects would have been masked when simply adjusting for sex and not considering sex-stratified analyses. We now have preliminary data where we identified genetic variants that are associated with tinnitus in men, but not in women (consistent with our heritability study). Here, not having stratified these analyses by sex would have left us with no significant genetic
associations, and thus no insights into molecular mechanisms. Thus, for both the identification of environmental and genetic risk factors in humans, SABV has been essential," explains Cederroth.

Asked to comment on how considering SABV can improve biological knowledge or medical practice in his field, Cederroth breaks it down: "In the case of tinnitus, identifying genes that increase the risk of developing tinnitus in men will provide insights into the biology of tinnitus development, whereas understanding why the impact of tinnitus in women is greater than in men will increase our understanding of the neural mechanisms related to the severity of the disease. Not only will this lead to a greater understanding of the biology of auditory processes, but it will also help in designing optimal diagnostics (which might prove effective in one sex but not the other), and gender-specific therapeutic interventions."


A photograph of Elisabet Stener-Victorin, Professor at the Department of Physiology and Pharmacology

Elisabet Stener-Victorin: PCOS research

Elisabet Stener-Victorin's lab investigates the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine and metabolic disorder in women. PCOS is characterized by abnormally high levels of sex steroids, in particular, androgens. Although PCOS is considered a woman's disorder, recent clinical studies indicate that boys born to women with PCOS are also affected. Indeed, Stener-Victorin is currently testing the hypothesis that exposure to high levels of maternal androgens in utero affects the growing fetus, causing phenotypic changes in both female and male offspring -- changes that can even be passed on to subsequent generations. Such transgenerational effects of PCOS should therefore be examined in both sexes and, while she strives to do so, Stener-Victorin emphasizes the challenges: "We need more funding to have personnel to be able to do the research; also, all molecular analyses are double... Right now, we are starting a big transgenerational experiment. At the moment I don’t have funding to take on one more person that would be needed to follow both sexes, so we will focus only on females. This is directly against the 3R and very sad."


Jorge Ruas: metabolism research

Jorge Ruas' lab performs pre-clinical research on how the body uses energy (energy metabolism) in the context of physical exercise and in relation to muscle disease, obesity, and diabetes. In the broad field of metabolism, sex-specific differences have long been appreciated, and so the group run their experiments in both males and females, where possible: "Part of our goal is to detail the molecular mechanisms by which physical exercise is beneficial to human health, so we can propose therapies for metabolic disease. These mechanisms must be validated in males and females, so that they are valid for both sexes." Asked what would increase consideration of SABV among biomedical researchers, Ruas urges, "Report data on males and females when you present and publish your data. The relevance of the differences people find will encourage others to also look in both sexes."



To read the full interview with Christopher Cederroth, Elisabet Stener-Victorin and Jorge Ruas about SABV in research, please download the document above entitled, 'Q&A: KI researchers talk about SABV'.

Questions or comments? Please contact Tamsin Lindström at Grants Office.