Sex and gender, influenced by genetics, epigenetics, and environmental/social stressors, must be considered in the assessment of each patient.
SPECIAL REPORT: GENDER AND SEX ISSUES
Attention to sex and gender differences has been a long time coming. In 1986, the National Institutes of Health mandated that women and minorities be included in clinical research; this initiative was reinforced by the 1993 FDA guideline for the study and evaluation of sex differences in the clinical evaluation of drugs, which overturned the 1977 guideline that women of childbearing age should be excluded from early clinical studies and explicitly requested that the data be analyzed for gender differences.
Sex refers to genetic and biological differences, and gender reflects the impact of social constructs/expectations on roles and relationships, behaviors, expression of emotions, and power dynamics. Advances in personalized medicine that use genetic information or other biomarkers to make treatment decisions have demonstrated gender differences with some treatments. We now know that the interaction of genome and environment or experience can result in epigenetic changes – alterations in gene expression rather than mutations in DNA sequences, which can lead to the formation of heritable phenotypic changes in addition to the traditional genetic basis of inheritance. . This increases the complexity of the analysis if a problem is genome-based or gender-based, related to experienced social constructs and stressors, driven by environmental events impacting a parent that manifested in the offspring, or all of the above.
Thus, some conditions are specific to people born with the female sex (for example, ovarian disorders). Some may manifest in the same way but are more likely to occur in one gender than the other (for example, depression is twice as likely to occur in women as in men). In some cases, gender differences influence the expression of similar characteristics such as dramatic or erratic traits, emotional dysregulation, and interpersonal conflict, diagnosed as borderline personality disorder in women and narcissistic personality disorder or antisocial in men. Additionally, gender differences increase the risk of various environmental stressors such as childhood trauma/victimization among girls and LGBTQ+ youth.
Unfortunately, nearly 30 years after mandating the assessment of sex differences, the U.S. Food and Drug Administration has failed to follow up on requirements for meaningful analysis of sex differences in clinical trials. . Tracking menstruation in premenopausal women in clinical trials is rare, as are comparisons of outcomes in premenopausal women versus postmenopausal women or men. Very little has been done to assess gender differences in symptoms and treatments for conditions such as post-traumatic stress disorder (e.g., military sexual trauma and/or childhood sexual trauma affecting women versus trauma related to combat in men). Additionally, priority has not been given to finding treatments for conditions that disproportionately affect women, minorities, and LGBTQ+ people.
Until gender-sensitive assessment of the clinical presentation, acquisition of the necessary history, establishment of the correct diagnosis(es), assessment of comorbidities and individualization of treatment are the responsibility of all providers, and that the assessment of sex and gender differences is embedded in all research, the needs of our patients will not be met.
The focus of this special report will be on how sex and gender, influenced by genetics, epigenetics and environmental/social stressors, should be considered in the assessment of each patient. Specifically, we need to anticipate the potential effect of trauma, understand the impact of gender-based environmental biases/stressors, intervene early, and examine how sex steroids determine the timing of various symptoms, particularly in women. Our patients deserve nothing less.
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Dr. Clayton is David C. Wilson Professor and Chair of the Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia, with a secondary appointment as Professor of Clinical Obstetrics and Gynecology. She is the author of Satisfaction: women, sex and the quest for intimacy, published by Ballantine Books in 2007, and a publisher from 2005 Women’s Mental Health: A Comprehensive Handbook. ❒