Sex & Gender in Acute Care Medicine

1. Sex & Gender in Acute Care Medicine Chapter 1: Introduction

2. Chapter 1: Introduction Alyson J. McGregor and Esther K. Choo

3. Defining Sex and Gender • Sex – biological differences between men and women • Chromosomes (XX, XY), internal and external sex organs, and hormones • Gender – socially constructed roles, values, and personality traits that vary across societies over time

4. Do Sex and Gender Matter? • A 2001 report by the Institute of Medicine (IOM) affirmed that sex “should be considered when designing and analyzing studies in all areas and at all levels of biomedical and health related research” • Cited growing evidence for significant differences between men and women in every aspect of health and disease

5. Do Sex and Gender Matter? • Evidence-based research that forms the basis for the current practice model was primarily conducted on male cell lines and male rats • Results translated to middle-aged, average-sized Caucasian males • Lack of consideration of sex differences is considered a failure of biomedical science

6. Do Sex and Gender Matter? • Cardiovascular Disease (CVD) research is an example of the implications of sex and gender on clinical care and health outcomes • Historically, research on CVD has largely been performed on men • 1988 Physicians’ Health Study examined the benefits of aspirin in CVD prevention – included 22,000 male participants

7. Do Sex and Gender Matter? • The study’s finding that daily aspirin could prevent myocardial infarction (MI) was widely adopted into clinical practice – despite not being studied in women • US Preventive Services Task Force now gives sex-specific recommendations on aspirin use • Questions still remain about management of cardiac disease in women

8. Do Sex and Gender Matter? • US General Accounting Office (GAO) reviewed 10 prescription drugs withdrawn from market from 1997-2000 • Found that 8 of the 10 drugs were withdrawn due to adverse events occurring mainly in women • FDA’s Office of Women’s Health established in 1994 to examine and advocate for inclusion of sex and gender as critical variables in research

9. Evolution of Women’s Health

10. Evolution of Women’s Health • In the 20th century, new medications prescribed to pregnant women led to disastrous outcomes • Thalidomide – prescribed to alleviate morning sickness, caused severe limb abnormalities in developing fetuses • Diethylstilbestrol – prescribed to prevent miscarriage, later found to cause gynecological cancers in the daughters of women given the drug

11. Evolution of Women’s Health • In 1977, amidst public pressure, the FDA implemented policy that banned women of childbearing potential from clinical trials • Women became more reluctant to volunteer as study participants

12. Evolution of Women’s Health • Exclusion of women was also influenced by researchers’ concerns about cost (due to larger sample sizes) and biologic factors (hormonal fluctuations due to menstruation, pregnancy, menopause, etc.) • It was assumed that, despite known differences, men would be adequate proxies for outcomes in women

13. Identifying a Difference • In 1986, the NIH recommended but did not mandate that women be included in clinical studies • In an audit of 50 grant applications, 20% did not mention gender • >30% did not provide breakdown percentages • Some all-male studies gave no justification for women’s exclusion

14. Identifying a Difference • In 1991, the NIH created the Office of Research on Women’s Health (ORWH) • Recognition of the research gap for women was slowly becoming more apparent • Yet in 1992, the GAO reported that >60% of trials submitted to the FDA by pharmaceutical companies lacked female representation

15. Identifying a Difference • In 1993, the FDA reevaluated its policy and encouraged researchers to include minorities and women and provide subgroup analyses • Even after 1993, there were more reports of adverse events in women than men during post-market surveillance • In 1999, IOM formed a Committee on Understanding the Biology of Gender Differences

16. Identifying a Difference • This was IOM’s first major step in the area of sex-based science • IOM’s 2001 report, “Does Sex Matter?” presented scientific evidence in support of sex- and gender-based research and solidified sex and gender as important variables • Ultimately, calls to action alone have not been enough to change researchers’ behaviors – a multifaceted response is needed

17. Why Focus on Emergency Care? • A vast array of disease conditionsthat present at critical points in their management • Definitive action within minutes to hours (“treatment window”) is unique to EM • Access to a wide segment of the population • Ideal setting to observe how men and women differ in their presentations and responses to treatment

18. Why Focus on Emergency Care? • The study of sex and gender in EM is in its infancy • EM has begun to direct its efforts toward an increased understanding of sex and gender • 2014 national consensus conference set a research agenda • This book aims to bridge the gap between clinical EM practice and the growing certainty that sex and gender are significant in all aspects of disease

19. Introduction Questions 1. Which of the following terms and related definitions are inaccurate? (A) Sex = Classification of a person by chromosomal complement (B) Gender = A person’s self-representation as male or female. (C) Gender = Rooted in biology and shaped by environment and experience. (D) Gender Bias = unequal treatment in opportunities or expectations due to attitudes based on a person’s sex or gender. (E) None of the above Answer: (E) None of the above There is a continuous interaction between sex and gender. Health is determined by the biology of being female or male and its interaction within the social context of gender. References: 1. KlingeI. W, C. Sex and Gender in Biomedicine. Theories, Methodologies, Results. Universitatasverlag Gottingen; 2010.

20. Introduction Questions 2. A patient’s name is listed in the medical chart as Jane Smith, a 43 year-old female with the preferred pronoun of “he”. What is the preferred term for this patient? (A) Transgender Woman (B) Transgender Man (C) Transsexual Woman (D) Transsexual Man (E) None of the above Answer: (B) Transgender = A term for people whose gender identity, expression or behavior is different from that typically associated with their assigned sex at birth. Transgender Woman = A term for a transgender individual who currently identifies as a woman Transgender Man = A term for a transgender individual who currently identifies as a man Transsexual = An older term for people whose gender identity is different from their assigned sex at birth and who seek to transition from male to female or female to male. Many do not prefer this term because it is thought to sound overly clinical. Gender Identity = An individual’s internal sense of being masculine, feminine, or something else. Gender identity may be fluid and context dependent. Because gender is internal, one’s gender identity is not necessarily visible to others, although others will make assumptions about one’s gender. Reference: Adapted from National Center for Transgender Equality 1. Equality NCfT. Transgender Terminology. 1325 Massachusetts Avenue NW, Suite 700, Washington DC2014.

21. Introduction Questions 3. Which of the following conditions would be considered Intersex? (A) Klinefelter’sSyndrome (B) Turner Syndrome (C) SRYMale (D) Androgen Insensitivity (E) All of the above Answer: (E) All of the above Intersex is defined as reproductive anatomy and/or a chromosome pattern that does not fit typical definitions of male or female. Also known as Differences of Sex Development (DSD). Examples include Klinefelter’s Syndrome (XXY), Turner (XO), SRY-gene Male (XX with the sex-determining region Y protein on the X chromosome), Androgen Insensitivity or medical conditions such as Congenital Adrenal Hyperplasia. Reference: Adapted from National Center for Transgender Equality 1. Equality NCfT. Transgender Terminology. 1325 Massachusetts Avenue NW, Suite 700, Washington DC2014.

22. Introduction Questions 4. Which of the following would be considered a sex-specific condition? (A) Coronary artery disease (B) Pelvic Inflammatory Disease (C) Benign Prostatic Hyperplasia (D) Chronic Obstructive Pulmonary Disease (E) B&C Answer: (E) Sex-specific conditions are those that are specific to one sex. For instance, male sex-specific conditions include benign prostatic hyperplasia (BPH) and prostate cancer while female sex-specific conditions include pregnancy, uterine cancer, ovarian torsion and pelvic inflammatory disease. Reference: 1. WizemannT PM. Exploring the biological contributions to human health: does sex matter? J Women’s Health Gender Based Med 2001;10:433-9.

23. Sex vs Gender vs Gender Bias Effects The following are examples that demonstrate the appropriate use of the terms Sex, Gender, and Gender Bias in medicine. In each of the following examples, please identify whether the scenario or difference reflects a sex effect, a gender effect, or gender bias.

24. Sex vs Gender vs Gender Bias Effects Lung Cancer 1. Long-term cancer rates are heading in different directions for men and women. Over the last 38 years in the U.S., the rate of new lung cancer cases has fallen among men 29% while it has increased 96% among women. This is mostly due to smoking rates, which increased dramatically for women in the 1970s when cigarette companies began marketing specifically to them. “Torches of Freedom” was one popular slogan used to entice women to smoke. In contrast, lung cancer rates for women in Vietnam are lower than for men as it is generally considered ‘unladylike’ for women to smoke. Answer: Gender Effects 2. There are two main types of lung cancer: small cell lung cancer, and the more common non-small cell lung cancer (NSCLC). Rates for these two types of cancer are similar in women and men. However, there are additional subtypes within these two cancer types. When we compare the two most common types of NSCLC, we see that the rate of squamous cell carcinoma is 50 percent higher for men than for women, while adenocarcinoma is 21 percent higher for women. Answer: Sex Effect 3. Only 1% of women cited lung cancer as a top cancer affecting women, even though lung cancer kills almost 2x as many women as any other cancer. More than 71,000 women are estimated to die of lung cancer in the U.S. this year alone. Answer: Gender Bias *see next slide for references

25. Sex vs Gender vs Gender Bias Effects Lung Cancer Lung Cancer References: 1. U.S. National Institutes of Health. National Cancer Institute. SEER Cancer Statistics Review, 1975-2011. http://vietbao.vn/Suc-khoe/Tu-112010-cam-hut-thuoc-la-noi-cong-cong-tren-khap-VN/65185155/248/http://www.wpro.who.int/vietnam/media_centre/speeches/speech_wntd09.htm 2. American Heart Association. Women’s Lung Health Barometer: http://www.lungforce.org/womens-lung-health-barometer-infographic

26. Sex vs Gender vs Gender Bias Effects Chronic Obstructive Pulmonary Disease 1. Women are more susceptible to chronic airflow limitations due to smaller airways. When compared to men, there is a greater degree of airflow obstruction for a comparable amount of tobacco consumption. Answer: Sex Effect 2. Research has consistently demonstrated that irrespective of clinical presentation, women are more likely to be diagnosed with asthma while men are more likely to be diagnosed with COPD Answer: Gender Bias References: 1. Han, M.K. et al. 2007. Ender and chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 176(12), 1179-1184 2. Ohar, J., Fromer, L. Donohue, J.F. 2011. Reconsidering sex-based stereotypes of COPD. Primary Care Respiratory Journal. 20(4), 370

27. Sex vs Gender vs Gender Bias Effects Urinary Tract Infection 1. Half of all women experience a urinary tract infection during their lifetime. Anatomical proximity of genitourinary tract to the rectum and physiologic variations in uroepithelial receptors for pathogenic bacteria contribute to this susceptibility in women Answer: Sex Effects 2. The behavior of using spermicidal contraception also contributes to the high rate of observed presentations for urinary tract infections in women. Answer: Gender Effects Reference: 1. McLaughlin, SP and Carson, CC 2004. Urinary tract infections in women. Medical Clinics of North America