Volume 36 Number 4 | August 2022

Carlo Ledesma, MS, MLS(ASCP)CMSHCM, QLSCM, DLMCM, MT(AMT)

Carlo LedesmaMagnum Hirschfield, hailed as the father of transgender medicine, pioneered gender studies in the Institut für Sexualwissenschaft (Institute of Sex Research) in Germany, where he cared for transgender individuals and performed gender-affirming treatments, including psychotherapies, hormone treatments, and gender reassignment surgeries. Unfortunately, even with the early days of scientific pursuit, because of social stigmatization and lack of interest in research and medicine, much remains to be understood for gender incongruence (GI) or gender dysphoria (GD), a condition experienced by approximately one million Americans.4

The World Professional Association for Transgender Health (WPATH) publishes a Standard of Care document to provide guidelines to align practitioners in the care of patients with gender incongruence. The WPATH also has resources and conducts symposia to advance the scientific collaboration in understanding transgender medicine and health. Currently, the gender-affirming treatments include intensive psychotherapy, hormone treatments, and/or gender re-assignment surgical interventions.3

The effects of gender-affirming hormone treatment result in somatic changes that require laboratory measurements of hormone levels and metabolic panels, and most of the gender-affirming treatments are personalized. Providers would need to be guided with accurate laboratory information to assess effectiveness of hormone treatment and for monitoring any adverse effects that the treatment may have on the patient.

Medical Laboratory Education

Until recently, laboratory medicine has not fully embraced this aspect of medicine. Extremely limited educational materials are available in laboratory medicine and pathology texts to introduce the clinical laboratory aspects related to transgender health. Tietz Textbook of Laboratory Medicine and Henry’s Clinical Diagnosis and Management by Laboratory Methods have introductory concepts on the impact of gender-affirming hormone therapy (GAHT) in transgender patients.20,21

Our duty to the profession includes advocating for health equity in our practice. We teach our medical laboratory students diseases occurring in 0.1 percent of the population. We emphasize teaching students blood bank techniques to prevent events that occur <1 percent annually. We conduct risk assessments and formulate policies in practice for disasters that will unlikely occur. But we have not envisioned to include a segment of our population needing appropriate care. Our work in the medical laboratory is vital for them to receive the appropriate care they need. We educate our students and colleagues on issues that may not occur in our lifetime, but have we given time to address this issue that is happening right now?

Our knowledge of gender incongruence should extend beyond knowing the meaning of terminologies, and we should ensure that models of laboratory education incorporate the unique laboratory needs of the transgender population.

Diagnostic Stewardship

The effects of exogenous hormone treatment significantly improve the quality of life for patients with gender incongruence. However, the administration of exogenous hormones has physiologic effects that require careful analysis of tests and accurate reporting of results. Feminizing therapies can increase the likelihood of osteoporosis in transgender females, while masculinizing therapies have the potential to increase red blood cells and could place a patient at risk for cardiovascular diseases.7,8 Advanced laboratory practitioners and pathologists can provide consultation to align the clinical team in the appropriate selection of tests through evidence-based, value-based care that will promote health equity and patient safety.9

Information Systems: Sexual Orientation and Gender Identity

In recent years, the U.S. Department of Health and Human Services (HHS) mandated the inclusion of sexual orientation and gender identity as part of the incentivization program associated with the Meaningful Use of Electronic Health Records.7 One pillar of Meaningful Use is to accurately capture the transgender demographic in electronic medical records to provide equitable care.

A simple change in the infrastructure of information systems goes a long way to help eliminate healthcare inequities for transgender patients.3 An inclusive electronic health record (EHR) and laboratory information system (LIS) can be structured with a two-question demographic identification of one’s sexual orientation and gender identity in EHR.4,5 This method of documentation using someone’s gender at birth and current gender allows computer programs to identify what reference range could be used, denial of care would be prevented, and preventive tests can be recommended.

Unfortunately, despite the incentivization programs by HHS, recent studies reveal that only a quarter of patient records included gender identity data, and 1 percent of these indicated a transgender or nonbinary (TGNB) status.6

Gender-Inclusive, Evidence-Based Laboratory Medicine

The Association for Clinical Biochemistry and Laboratory Medicine Pre-Analytical Phase Special Interest Group (ACB-PA-SIG) suggests that LIS functionalities be updated to reflect appropriate reference intervals, editing, and upgrading patient demographics without altering historical information and other functionalities that would allow safe interpretation of laboratory results.22 Other updates in LIS infrastructure should include systems and processes to document variables unique to transgender patients. From a patient safety standpoint, applying appropriate reference intervals based on their clinical status will allow appropriate interpretation of laboratory results leading to improved patient care.

Efforts to understand the health of individuals with gender dysphoria and gender incongruence have made considerable progress. Cheung et al. developed an approach to interpreting laboratory tests affected by gender-affirming therapy that is based on affirmed gender (electrolytes, lipids, hemoglobin, iron studies, estradiol, testosterone, and creatinine/eGFR) or gender at birth (hs-CRP and PSA).14,15 The Endocrine Society published clinical guidelines for treatment and laboratory monitoring of patients undergoing GAHT, juxtaposed with the World Professional Association for Transgender Health’s Standards of Care (WPATH SOC), providing guidelines in the clinical management of patients on GAHT.1,3,11

Medical laboratories have made noteworthy progress in promoting evidence-based, gender-inclusive laboratory medicine. Dina Greene, PhD, DABCC, led the research team to develop appropriate reference ranges for gender-affirmed patients. In a collaboration between Kaiser Permanente and the University of Iowa, Dr. Greene developed the reference ranges for some laboratory tests that are applicable to gender-affirmed patients.16 Published in the Journal of Applied Laboratory Medicine, Dr. Greene’s team has successfully developed institution-led reference intervals for laboratory tests commonly used for patients in stable hormone therapy. These laboratory tests include complete blood counts, testosterone, estrogen, SHBG, LH, FSH, AMH, progesterone, prolactin, electrolytes, lipids, and HbA1c.23,24

Summary

With patient safety at the core of our practice and guided by our duties to the profession, society, and to our patients, laboratory medicine is a vital component to realize gender-inclusive practice in medicine; high-quality diagnostic stewardship promotes patient safety. The success of gender-affirmation treatments is not limited to laboratory and physical evidence of gender-affirmation.

This is merely the beginning of our journey to understand transgender health as we aim to understand the short- and long-term sequelae of gender affirmation treatments. So, I extend my plea to my colleagues in the medical laboratory profession.

We pledged to the profession that we would continue to ensure that each patient receives care that is safe, effective, efficient, timely, equitable, and patient-centered.

We pledged that we would be the instruments of change, that we would change conditions necessary to advance the best interests of patients.

Today is that day. This is the moment in our careers where we must take action to advance our profession and be the instrument of change to advocate for the patients who need our expertise to ensure they receive high-quality and safe care.

Lastly, I devote most of my life to this profession that I will always love. As a member of the LGBT community, I plead to my colleagues and to the profession to help our friends achieve appropriate medical care that every human deserves, because we, too, deserve our day in the sun.

References
  1. World Professional Association for Transgender Health. (2012). Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People [7th Version]. https://www.wpath.org/publications/soc
  2. Steakley, James D. “Per scientiam ad justitiam Magnus Hirschfeld and the Sexual.” Science and homosexualities (1997): 133.
  3. Murad, M. H., Elamin, M. B., Garcia, M. Z., Mullan, R. J., Murad, A., Erwin, P. J., & Montori, V. M. (2010). Hormonal therapy and sex reassignment: A systematic review and meta-analysis of quality of life and psychosocial outcomes. Clinical endocrinology, 72(2), 214-231.
  4. Meerwijk, Esther L., and Jae M. Sevelius. “Transgender population size in the United States: a meta-regression of population-based probability samples.” American journal of public health 107.2 (2017): e1-e8.
  5. James, Sandy, et al. “The report of the 2015 US transgender survey.” (2016).
  6. Kronk, Clair A., et al. “Transgender data collection in the electronic health record: Current concepts and issues.” Journal of the American Medical Informatics Association 29.2 (2022): 271-284.
  7. Thompson, H. M., Kronk, C. A., Feasley, K., Pachwicewicz, P., & Karnik, N. S. (2021). Implementation of Gender Identity and Assigned Sex at Birth Data Collection in Electronic Health Records: Where Are We Now? International Journal of Environmental Research and Public Health, 18(12), 6599.
  8. Tate, C. C., Ledbetter, J. N., & Youssef, C. P. (2013). A two-question method for assessing gender categories in the social and medical sciences. Journal of sex research, 50(8), 767-776.
  9. Swanson, K., Dodd, M. R., VanNess, R., & Crossey, M. (2018). Improving the delivery of healthcare through clinical diagnostic insights: a valuation of laboratory medicine through “Clinical Lab 2.0.” The Journal of Applied Laboratory Medicine, 3(3), 487-497.
  10. Madsen, Milou Cecilia, et al. “Erythrocytosis in a large cohort of trans men using testosterone: a long-term follow-up study on prevalence, determinants, and exposure years.” The Journal of Clinical Endocrinology & Metabolism 106.6 (2021): 1710-1717.
  11. Feldman, J., Brown, G. R., Deutsch, M. B., Hembree, W., Meyer, W., Meyer-Bahlburg, H. F., … & Safer, J. D. (2016). Priorities for transgender medical and health care research. Current opinion in endocrinology, diabetes, and obesity, 23(2), 180.
  12. Crawford, James M., et al. “Improving American Healthcare Through “Clinical Lab 2.0” A Project Santa Fe Report.” Academic pathology 4 (2017): 2374289517701067.
  13. Agana, M. G., Greydanus, D. E., Indyk, J. A., Calles Jr, J. L., Kushner, J., Leibowitz, S., … & Cabral, M. D. (2019). Caring for the transgender adolescent and young adult: Current concepts of an evolving process in the 21st century. Diseasea-Month, 65(9), 303-356.
  14. Cheung, A. S., Lim, H. Y., Cook, T., Zwickl, S., Ginger, A., Chiang, C., & Zajac, J. D. (2021). Approach to interpreting common laboratory pathology tests in transgender individuals. The Journal of Clinical Endocrinology & Metabolism, 106(3), 893-901.
  15. Humble, R. M., Imborek, K. L., Nisly, N., Greene, D. N., & Krasowski, M. D. (2019). Common hormone therapies used to care for transgender patients influence laboratory results. The journal of applied laboratory medicine, 3(5), 799-814.
  16. Carpenter, A. A. “Transgender adult reference intervals taking shape.” CAP TODAY (2019).
  17. Pagano, Monica B., et al. “Transfusion services operations during the COVID-19 pandemic: Results from AABB survey.” Transfusion 60.11 (2020): 2760.
  18. Rivers, Patrick A., Aram Dobalian, and Francesco A. Germinario. “A review and analysis of the clinical laboratory improvement amendment of 1988: compliance plans and enforcement policy.” Health Care Management Review 30.2 (2005): 93-102.
  19. Dhruva, Sanket S., and Rita F. Redberg. “Evaluating sex differences in medical device clinical trials: time for action.” Jama 307.11 (2012): 1145-1146.
  20. Rifai, Nader. Tietz textbook of clinical chemistry and molecular diagnostics-e-book. Elsevier Health Sciences, 2017.
  21. McPherson, Richard A., and Matthew R. Pincus. Henry’s clinical diagnosis and management by laboratory methods E-book. Elsevier Health Sciences, 2021.
  22. Costelloe, Seán J., and Sophie Hepburn. “Management of transgender patients in Laboratory Information Management Systems–Moving on from binary and ternary logic.” Annals of Clinical Biochemistry 58.4 (2021): 264-266.
  23. Greene DN, McPherson GW, Rongitsch J, et al. Hematology reference intervals for transgender adults on stable hormone therapy. Clin Chim Acta. 2019; 492:84–90.
  24. Humble, Robert M., et al. “Reference Intervals for Clinical Chemistry Analytes for Transgender Men and Women on Stable Hormone Therapy.” The Journal of Applied Laboratory Medicine (2022).

Carlo Ledesma is the Program Director, Medical Laboratory Technology, at Rose State College. He is also a Doctor of Clinical Laboratory Science Student at the University of Kansas Medical Center and is a DCLS Resident at Oklahoma City VA Medical Center.