Management of transgender patients in Laboratory Information Management Systems – Moving on from binary and ternary logic

The term ‘transgender’ describes individuals whose gender identity (GID) differs from their sex assigned at birth (SAB). Despite recent societal shifts in recognition and awareness of transgender issues in many countries, this population faces significant disparity in health-care access, based on prejudice, health-care costs and lack of expertise.^1–3

The Laboratory Medicine community has a duty of care to provide safe and appropriate test analyses and interpretation for transgender patients, during transgender hormone therapy (THT) and at all other times. Transgender patients present particular challenges to laboratories in how to adequately, safely and efficiently record information relating to GID and gender history, in a manner that is acceptable to the individual. Such information may inform the choice, interpretation and reporting of laboratory investigations in this patient group.

Key barriers to effective provision of laboratory services for transgender patients include: lack of information from patients and clinicians; lack of patient consent to share their transgender status; laboratory requirements for information which may clash with legal imperatives or patient preference; underappreciation of the risks of current systems among laboratories, clinicians and the transgender community. In addition, the outdated functionality of the typical Laboratory Information Management System (LIMS) makes the management of transgender patients somewhat cumbersome and error-prone.

Gender Recognition Acts make provision for adults over 18 years of age to change their legal gender so that it matches their (binary) GID. Gender Recognition Certificates can be obtained based on a diagnosis of gender dysphoria in the United Kingdom (UK), ⁴ or via a self-determination process in the Republic of Ireland (ROI). ⁵ In the rest of Europe, the situation varies starkly between countries, and sterilization is a prerequisite to changing legal gender in some jurisdictions, while the situation in the United States varies state to state.

Despite the social changes observed in certain countries, LIMS, and health-care information technology systems in general, remain inflexible for the purposes of recording multifactor gender information. Generally, LIMS record legal name and gender, date of birth and a Patient/Hospital/NHS number (UK only) as key patient identifiers, ⁶ and most LIMS have ternary gender options only, i.e. ‘Male’, ‘Female’ and ‘Unknown/Other’. Thus, there are two key issues when registering transgender patients in most LIMS: there may not be gender categories available to adequately record the individual’s GID, and there are often no LIMS fields available to record gender information other than GID. Generally, where a gender factor is used in the LIMS rules base, be it for the application of gender-specific reference intervals (RIs), in formulae with gender-specific variables, or for the blocking of certain test requests, these functions will use a single gender variable, corresponding with a binary, or ‘Unknown/Other’, GID. However, depending on the analysis under consideration, information on other aspects of a patient’s gender history may influence the interpretation of contemporary laboratory results.

When an individual’s GID is changed on a LIMS or where a patient chooses to obtain an entirely new patient/hospital/NHS number, there may be no record of these changes, or anything on their record to indicate they are transgender. Although these systems place patient dignity and preference, and legal requirements, at their core, there can be unintended risks for transgender patients where the recorded GID influences the care or investigations they receive.

Depending on the test, and although these may be difficult to obtain, interpretation of laboratory results may require knowledge that the patient is transgender, the type and timings of therapeutic or surgical interventions and the SAB (or chromosomal gender). Where available, these data would ideally be retained in LIMS for future use in an appropriate form. Even where a full gender history is available, LIMS often lack the capability to accurately and discretely capture, store and manipulate these data as may be required for: generation of calculated test results; the automated application of appropriate reference intervals (RIs) or comments; automated gatekeeping of tests; or reflex testing in transgender patients. Such processes are vital in those pathology disciplines with a high-throughput workload such as Clinical Biochemistry, or where patient safety relies fundamentally on accurate patient demographics, such as blood transfusion. ⁷ However, where only the GID is known, there is a high probability that transgender patients will be categorized as cisgender on LIMS. The incorrect application of RIs or factors in laboratory equations based on binary or ternary gender categories are not trivial and can result in increased clinical risk for transgender patients due to inappropriate addition, blocking or removal of test requests, as well as incorrect interpretation of laboratory test results as discussed.

Calculations for estimated glomerular filtration rate (eGFR) which use creatinine (e.g. MDRD and CKD-EPI), use binary gender factors in their calculation and are perhaps the most common calculated test result in Clinical Chemistry. A startling case discusses a transgender male, kept off a kidney transplant list for over one year due to a lack of understanding of which was the appropriate gender factor to use when calculating their eGFR. ⁸

Rules using binary gender variables may lead to rejection of tests as inappropriate, for example prostate-specific antigen (PSA) in patients classified as ‘female’ on LIMS or CA125 in males. Rejecting PSA in transgender females, classified on LIMS as cisfemales, may be inappropriate since prostate cancer in transwomen is well reported in the literature. ⁹ , ¹⁰

It is important that LIMS functionality exists to assign RIs for transgender patients appropriately, and that cisgender RIs corresponding with the GID are not routinely applied. The suitability of a RI or clinical cut-off for use in care provision for a given individual may be influenced by physiology, ethnicity, genetics, GID and therapeutic interventions. Therefore, application of gender-specific RIs based on GID is not always appropriate or safe in transgender patients, particularly those on THT. The effects of THT on laboratory analyses are analyte dependent. Values may change to the cisgender range corresponding with the GID, as occurs with haemoglobin and haematocrit. ¹¹ However, for many other analytes, such as creatinine, cholesterol, HDL, LDL, triglyceride, ALT and AST, there are conflicting reports in the literature as to the effects on RIs, perhaps reflecting the highly personalized nature of THT. ¹² Thus, it is difficult at present for laboratories to conclude whether transgender-specific RIs are required, what these might be, or what ranges or comments are best appended to patient reports for transgender patients.

Given the inflexibility of LIMS systems, laboratories may be using potentially inappropriate systems to record information on transgender patients such as patient record alerts or flags, free text comments, or spreadsheets and databases.

A key question is how LIMS manufacturers are addressing the issues discussed. A Canadian survey suggested that some LIMS manufacturers already had, or were developing, functionality to record biological sex and gender information other than SAB, and that several were cautiously developing systems for the use of transgender RIs. Few LIMS providers claimed that their customers were enquiring about enhanced functionality. ¹³

The Association for Clinical Biochemistry and Laboratory Medicine Pre-Analytical phase Special Interest Group (ACB-PA-SIG) suggest that now is an opportune time to directly address many of the issues discussed in relation to LIMS and transgender patients. As a starting point, the group suggests LIMS have the following functionality: patient preferred demographics (name, pronoun and GID); categories to allow safe interpretation of all laboratory results and calculations for transgender patients in an automated manner (e.g. SAB, chromosomal gender, details of surgical and therapeutic interventions, gender history and chronology); record where a patient has given consent for their gender history to be shared for clinical care; flexible rules to allow variables be used for the automated application of appropriate RIs, calculations and clinical cut-offs; and easier processes for editing gender demographics without alteration of RIs applied to historic data.

The ACB-PA-SIG propose that key stakeholders convene a working group to redesign and standardize LIMS so that they can be used for transgender patients while keeping patient safety and dignity at their core. Stakeholders should include UK and ROI representatives from: the ACB-PA-SIG; Clinical and Academic experts in transgender medicine; LIMS providers; appropriate Pathology disciplines not represented by the ACB-PA-SIG; National Informatics and Health and Safety bodies; Transgender support group members; Psychologists and legal experts with expertise in discrimination law and general data protection regulations.