Humans are socialized to interact with people differently based on their gender expression—and those preconceptions also impact individuals’ experiences within the healthcare system. Clinical professionals must work not only to address their own biases regarding patients’ gender identities, but also to ensure they are providing appropriate gender- and sex-specific medical care.
For this reason, AACC and the College of American Pathologists recently sponsored a taskforce of physicians and laboratory scientists to develop guidance for gender inclusion within the practices of laboratory medicine and pathology. The taskforce will outline tangible steps that laboratories can take to reduce discrimination and improve the healthcare experience for transgender people.
As we await this forthcoming guidance, we hope laboratory staff have already begun to embrace gender diversity, beginning when patients first present to the lab.
UNDERSTANDING IDENTITY, GENDER, AND SEX
Humans define themselves and others with identities: “I am a basketball player;” “She is an artist;” “They are Mexican.” Identity is defined as “the fact of being who or what a person or thing is.” Often, these traits appear naturally, even as our cultural expressions are complex amalgams of nature and nurture. Gender is a function of the social, psychological, cultural, and behavioral aspects of being a man, woman, or nonbinary human. It is not a choice or a biological assignment, but rather an inherent identity that significantly contributes to a person’s sense of belonging.
In contrast, sex refers to the chromosomal make-up that prescribes the development of gonads and endogenous sex-hormone expression.
Cisgender people have experienced only congruence between their sex assigned at birth and their gender identity. Even so, cisgender men and women will have different medical experiences based on their sex and gender. Sex-specific medical care is important for cancer screening, fertility testing and treatment, and workups for other anatomical-based conditions. Gender-specific medical care is a function of socialization and current sex-hormone composition (endogenous and/or exogenous).
Some well-recognized healthcare disparities relate to sex and gender biases within medicine. Gender impacts how likely a person is to receive standard-of-care cardiology services, for example. For many years, clinicians were taught that women with acute coronary syndromes present in an “atypical” or clinically abstract manner, potentially leading to delayed diagnoses and treatment.
In fact, men and women simply present with different signs and symptoms. In addition, we now know that high-sensitivity troponin is an excellent biomarker for acute coronary syndrome in women. But historic teaching patterns and unconscious biases may lead to people who present as masculine being triaged differently than those who present as feminine.
IMPLICATIONS FOR LAB MEDICINE
In laboratory medicine and pathology, we often are tasked with generalizing populations. Our reference intervals are derived using practical approaches, such as defining “normal” as the middle 95% of the population distribution.
For tests with sex-specific distributions, we derive and use separate reference intervals for men and women. When electronic medical records (EMRs) indicate that a person is male or female, the applicable reference interval is triggered in the system. However, whether an EMR differentiates between sex and gender is inconsistent, varying among and within institutions.
Developing a simple, standardized approach for identifying sex and gender in our electronic systems is fundamental to improving care and respecting people of all genders. Sex fields should be used as needed for organ inventory, while gender fields should direct healthcare professionals on the appropriate pronouns to use for patients at the time of sample collection. Similarly, reference intervals and pathology reports should include gender neutral language. Using patients’ preferred names whenever interacting with them benefits everyone, including those who are gender diverse.
Anatomy often dictates the type of screening a person needs. For example, cervical cancer screening applies only to people with a cervix. A cisgender woman who has undergone a complete hysterectomy will no longer qualify for regular screening, but a transgender man with natal reproductive organs will. For the latter example, the EMR may indicate that the patient is male. Ensuring that laboratory information systems (LISs) do not cancel tests based on anatomical assumptions is important for providing equitable care.
Similarly, prostate-specific antigen (PSA) and human chorionic gonadotropin (hCG) are often thought to apply only to men and women, respectively. However, if a transgender woman has a PSA result of 100 ng/mL, this result should be flagged, irrespective of the sex/gender marker that the lab receives. Because the lack of standardized interfaces between the EMR and LIS may prohibit a laboratory from identifying a patient’s assigned sex, results for critical tests that fall outside of the reference interval should always be flagged.
CURRENT DISCUSSIONS, FUTURE POSSIBILITIES
Electronic medical records and lab information systems increasingly include functionality to record a patient’s sex assigned at birth, gender identity, and sexual orientation in addition to legal sex. While there is still wide variability across products, the availability of these sexual orientation/gender identity (SOGI) fields opens possibilities for more sophisticated approaches for flagging and interpreting test results.
For instance, a clinician’s interpretive comment about changes to a patient’s hemoglobin/hematocrit that are possibly due to gender-affirming hormones could be appended to the test results of a person identifying as transgender or nonbinary in the gender identity field. For anatomic pathologists, SOGI fields within the EMR and LIS could allow these professionals to quickly recognize that a specimen which seems discordant with a patient’s legal sex could be explained by the fact that the patient has had gender-affirming hormones and/or surgery.
Some tests have sex-specific reference intervals that are driven by endogenous hormone concentration. Testosterone stimulates erythropoiesis, for example; therefore, there are clearly observable differences in hemoglobin and hematocrit levels between boys and girls that begin at puberty and continue throughout adulthood. That means that transgender men on stable testosterone hormone therapy will have hematology results similar to cisgender men, whereas transgender women on stable estradiol therapy will have values similar to cisgender women.
Other tests are less straightforward. The concentration of creatinine, a byproduct of muscle mass, tends to be higher in men than women. While testosterone contributes to muscle mass, lifestyle factors can also play a large role. For instance, a transgender man who lifts weights and takes testosterone during gender transition has multiple factors that may influence creatinine relative to baseline.
Selecting appropriate reference intervals for creatinine in patients receiving gender-affirming therapy, and more importantly, determining which sex-specific variable to use in eGFR equations, is a topic of current discussion between the fields of clinical chemistry and nephrology.
Even though laboratorians generally work “behind the scenes,” there are many ways we can improve inclusion of gender diversity within clinical practice. Normalizing that sex and gender are different can go a long way towards creating an accepting clinic experience. It’s also important to keep in mind that the pre-analytic process begins when a patient presents to the lab. Creating an inclusive environment for everyone means embracing quality from the start.
Dina Greene, PhD, DABCC, FADLM, is a clinical associate professor of chemistry at the University of Washington and an associate laboratory director at LetsGetChecked in Seattle, Washington. Email: [email protected].
Matthew D. Krasowski, MD, PhD, is clinical professor of pathology, Walter I. Bierring Professor of Clinical Education, medical director of clinical chemistry and point of service laboratories, and vice chair for clinical pathology and laboratory services at University of Iowa Healthcare in Iowa City, Iowa. Email: [email protected]