Longitudinal Changes in Hematologic Parameters Among Transgender People Receiving Hormone Therapy

Ana Antun; Qi Zhang; Shalender Bhasin; Andrew Bradlyn; W. Dana Flanders; Darios Getahun; Timothy L. Lash; Rebecca Nash; Douglas Roblin; Michael J. Silverberg; Vin Tangpricha; Suma Vupputuri; Michael Goodman

Disclosures

J Endo Soc. 2020;4(11) 

In This Article

Abstract and Introduction

Abstract

Context: The effect of gender-affirming hormone therapy (HT) on erythropoiesis is an area of priority in transgender health research.

Objective: To compare changes in hematologic parameters and rates of erythrocytosis and anemia among transgender people to those of cisgender controls.

Design: Longitudinal observational study.

Participants and Setting: We compared 559 transfeminine (TF) and 424 transmasculine (TM) people enrolled in 3 integrated health care systems to matched cisgender referents.

Interventions and Outcome: Hormone therapy receipt was ascertained from filled prescriptions. Hemoglobin (Hb) and hematocrit (Hct) levels were examined from the first blood test to HT initiation, and from the start of HT to the most recent blood test. Rates of erythrocytosis and anemia in transgender participants and referents were compared by calculating adjusted hazard ratios and 95% confidence intervals (CI).

Results: In the TF group, there was a downward trend for both Hb and Hct. The corresponding changes in the TM cohort were in the opposite direction. TM study participants experienced a 7-fold higher rate (95% CI: 4.1–13.4) of erythrocytosis relative to matched cisgender males, and an 83-fold higher rate (95% CI: 36.1–191.2) compared to cisgender females. The corresponding rates for anemia were elevated in TF subjects but primarily relative to cisgender males (hazard ratio 5.9; 95% CI: 4.6–7.5).

Conclusions: Our results support previous recommendations that hematological parameters of transgender people receiving HT should be interpreted based on their affirmed gender, rather than their sex documented at birth. The clinical significance of erythrocytosis following testosterone therapy, as well as anemia following feminizing HT, requires further investigation.

Introduction

Masculinizing and feminizing hormones constitute an important component of medical gender affirmation among transgender people.[1,2] For transfeminine (TF) individuals, the gender-affirming hormone therapy (HT) usually includes estrogens, often in combination with antiandrogens.[3] For transmasculine (TM) individuals, hormonal gender affirmation involves the administration of testosterone.[4] Short- and long-term benefits and risks of HT represent an emerging field of clinical research, with many open questions.[5–9]

A specific area of both research and practical interest is the effect of gender-affirming HT on various laboratory parameters that can occur following the administration of feminizing and masculinizing hormones. In particular, HT use is expected to stimulate erythrogenesis, as evidenced by elevated Hb or Hct levels in TM patients, and to produce an opposite effect in TF persons undergoing gender affirmation treatment.[10–12]

Although changes in erythrogenesis after initiation of gender-affirming therapy are expected to be mostly physiological, the laboratory values during the transition period may be interpreted as abnormal if based on inappropriate reference ranges.[12,13] In addition, there is a concern that testosterone therapy may produce clinically significant erythrocytosis in TM patients.[9,14]

Previous clinical studies consistently reported significant increases in Hct and Hb following the initiation of testosterone therapy among TM patients, whereas feminizing hormone therapy was shown to have an opposite effect.[15–21] On the other hand, relatively limited data are available on the temporal trajectories of Hb and Hct changes among TM and TF subjects receiving HT relative to cisgender referent groups. Moreover, little information is available regarding the incidence of erythrocytosis and anemia in relation to gender-affirming hormone therapy, especially over extended periods of time.

To help with closing these knowledge gaps, we used data from a large cohort study nested in integrated health care systems that allowed access to electronic health records (EHR) and permitted efficient identification and follow-up of hard-to-reach population subgroups, such as transgender people. The aims of the present study were to examine longitudinal changes in the main hematologic parameters among TF and TM persons before and after HT initiation, and to compare trajectories of these parameters, as well rates of erythrocytosis and anemia, to those of matched cisgender individuals.

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