Reference intervals are the most common decision support tool used for interpretation of numerical pathology reports. Results which fall outside of this ‘normal’ range may indicate a health problem. Unfortunately, due to a lack of medical research, there are no reliable reference intervals specific to transgender patients in most instances. Dr Ada Cheung explains that this could put patients at risk of misdiagnosis and encourages trans and intersex people to be aware of pathology testing related to themselves.

Dr Cheung is an endocrinologist at Austin Health and wrote the first ever set of guidelines to guide doctors in the care of transgender and gender diverse Australians.

“Estimates suggest that 0.2–4.0% of the population are transgender or gender diverse (TGD) and yet are underrepresented in medical research. Although essential to assist with interpretation of several pathology parameters, transgender guidelines for reference intervals do not currently exist.

“Trans people may understandably be reluctant to reveal their gender identity due to the risk of discrimination. We therefore want to work with the community to improve all healthcare and pathology settings, and ensure that care is medically safe at all times. We don’t want to “out” people, but we need to communicate sensitively that there will be situations where it is medically important to disclose certain information such as gender identity. From the laboratory perspective, we need to make sure that we have the correct processes in place to report the correct reference intervals and reference limits,” said Dr Cheung.

Reference intervals are established by taking the results of large numbers of healthy people and calculating what is typical for them. Factors such as age, muscle mass, organ size, sex and ethnicity can affect results, so often a series of reference intervals is established. Many tests with sex-specific reference limits are different because of either body composition or organ size.

In addition, some gender-affirming hormone therapies significantly influence sex steroid concentrations, thereby influencing factors such as haemoglobin and body composition changing fat and muscle mass. The duration of gender-affirming hormone therapy also needs to be taken into consideration.

“There are some dangers associated with the non-disclosure of presumed sex at birth, and therefore a number of healthcare situations where disclosure of gender assigned at birth is advisable for safety reasons. For example, an incorrect blood transfusion could cause haemolytic disease of the newborn in a future pregnancy. Another example is misdiagnosis of a heart attack – as hearts are bigger in people whose birth sex is male, their troponin levels are naturally higher. A health professional may potentially misinterpret a troponin result without knowing the person’s birth sex.

“I think if there is any doubt on which reference interval we should be using, then we should report on both. We know that doctors would prefer to have both available to them to enable interpretation when they may be unsure of which reference interval to use or in the early phase of gender-affirming hormone therapy.

“In the ideal setting, we need to make sure that it is safe and affirming so that trans people do not fear being discriminated against by anybody accessing their medical information or pathology results. Clear communication will be paramount,” said Dr Cheung.

Chemical pathologist and former Deputy CEO of the RCPA, Dr Janet Warner, sits alongside Dr Cheung on a dedicated Task Force established by the College to tackle this issue. Dr Warner explains one of the main problems is that medical systems have been slow to properly accommodate transgender patients.

“The inflexibility of electronic medical records in documenting affirmed gender is a major challenge in transgender healthcare, especially in pathology/laboratory medicine. The health computer system is binary; therefore, it is not possible to record a patient’s gender identity when applying reference intervals for a different gender, which may be more medically appropriate.

“As a general rule, disclosure of sex assigned at birth and hormone treatment details is recommended in a healthcare setting where laboratory tests with sex-specific reference limits or treatment implications are needed. Ideally this should be visible on the pathology request form so that the laboratory can place the correct reference limits and interpretation on the report,” said Dr Warner.