Do We Need Transgender-specific Reference Ranges for Common Laboratory Tests?

Who is transgender?

The sex of an individual is typically assigned at birth based on the appearance of the external genitalia. Chromosomal testing can determine whether a person is biologically male (1 X chromosome and 1 Y chromosome [XY]) or female (2 X chromosomes [XX]).

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However, how a person identifies (gender identity) is unrelated to their sex at birth and based on their personal feelings and self-concept. Individuals can identify as a man, a woman, or as a nonbinary gender, which means that they do not identify as one of the two traditionally used genders of man or woman.

Sexual orientation refers to whether a person identifies as bisexual, heterosexual (straight) or homosexual (gay or lesbian), or other sexual orientation. For many persons who are transgender, the traditional sexual orientation categories may also be inadequate in describing their personal experience.

The term transgender describes individuals who live their lives with a gender identity that differs from the one assigned at birth. Furthermore, people who do not fit into the description of either binary male or female are also classed as transgender, also known as genderqueer.  

The older term transsexual refers to transgender persons who have undergone surgery or take medication to change physical characteristics to align them with their gender identity better. There are many other words that transgender persons use to describe themselves, which reflects the reality that each person experiences sexuality and gender uniquely.

Obstacles in healthcare for the transgender population

Transgender people may feel unsafe to reveal their gender identity, as they fear prejudice from the healthcare sector. These prejudices mostly arise from a lack of knowledge about gender identity by healthcare professionals. Discrimination may occur simply because  a general practitioner assumes a patient´s gender based on appearance.

Problems in the laboratory may arise if the name of the person does not match their gender identity; this can lead to the rejection of specimens for analysis. For example, they could assume that a pregnancy test should not be performed in a patient who identifies as a man, although this person may be physically able to bear children.

These discriminatory practices, whether intentional or resulting from lack of knowledge, lead to inadequate healthcare access for transgender individuals.

Training laboratory staff is the most important step to take towards developing ranges for specimen testing for transgender persons.

Complications with laboratory tests of the transgender population

Standardized laboratory ranges, which only allowing patients to be classed as male and female, is a major challenge with surgical pathology and clinical laboratory tests results of transgender patients.

Furthermore, it becomes even more difficult with sex-specific reference ranges (for example, liver enzyme tests, creatinine, and hematocrit levels). Due to the lack of scientific studies on this topic, it is a challenge for healthcare providers to decide upon a “normal” reference range for each individual patient and to interpret their results.

Solutions for transgender-specific reference ranges

One retrospective study by Roberts et al. from 2014 concluded that new laboratory reference ranges need to be developed to aid in the interpretation of laboratory results for transgender patients. One important factor includes that the heterogeneity of these values within the transgender population could be affected by hormonal and surgical therapies, which are currently not well-understood.

For example, the prostate-specific antigen (PSA) levels, which are used for screening for prostate cancer, falsely decrease with long-term antiandrogenic therapy. Therefore, a woman with XY chromosomes may be at risk for prostate cancer, but hormonal therapy makes test interpretation challenging.

The binary gender assignment system for laboratory reference ranges makes it difficult for transgender patients, not only medically, but the consequences are also seen emotionally especially when inappropriate reference ranges are used.

Some transgender persons choose to undergo long-term hormone therapy with either estrogen or testosterone. Both hormones change the appearance of the patient over a time period. Thus, it is very important to use laboratory services to keep track of hormone levels.

The reports by Jacobeit et al. and Roberts and Kraft both confirmed that the standardized male or female reference ranges are not appropriate for transgender people. Some markers would fit the male reference ranges and others the female ranges.

Markers such as hemoglobin, hematocrit, and lipid levels would be expected to change over time for someone taking hormone therapy, but these changes should not be assumed to be evidence of an abnormality.

In 2006 Feldman and Goldberg suggested the following categorization on binary laboratory forms:

• Using sex which was assigned at birth and the patients is neither on hormone therapy nor had testicles or ovaries surgically removed.
• If patients are undergoing hormone therapy and testicles or ovaries were removed, the gender which was aligned with hormone treatment should be used (Male for testosterone therapy and F for estrogen treatment).
• Gender should be varied if transitioning is currently taking place. In this case, it is best to explain the chosen option to the patient and ask if it is appropriate for them.

Are transgender-specific reference ranges necessary?

Although awareness of the medical needs of the transgender population is increasing and stigmatization is decreasing, barriers remain. Laboratory test reference ranges should become easier to interpret for all populations, including transgender people.

This would be beneficial for pathology staff members, those working in phlebotomy, and employees in transfusion medicine, as the interpretation of test results would become easier.

Special training could help healthcare workers to understand health issues transgender patients could deal with. Additionally, interpreting specimens and biopsies of transgender individuals would become easier to handle with this training.

Transgender persons deserve the same quality of healthcare as other patients. Aligning laboratory reference ranges to reflect the full range of genders and obtaining detailed medical histories, including gender identity and history of surgery or medication use, will help providers and laboratories choose and interpret tests and provide the most appropriate care.

Further Reading

• All Blood Test Content
• NIPT Test (Noninvasive Prenatal Testing)
• Blood Type Testing
• Understanding Laboratory Blood Test Results