Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European network for the investigation of gender incongruence
Open accessAbstract
In trans persons on gender-affirming hormonal treatment, a decrease (in trans women) or increase (in trans men) in hematocrit is often observed. Reference ranges for evaluation of hematocrit levels in trans persons have not been established. This prospective cohort study is part of the European Network for the Investigation of Gender Incongruence (ENIGI). At the Ghent and Amsterdam sites, we included 625 hormone-naïve trans persons. Gender-affirming hormonal treatment was initiated at the first visit. In trans men, serum hematocrit (Hct) levels increased during the first year (+4.9 Hct %, 95% CI 3.82-5.25), with the most pronounced increase during the first 3 months (+2.7 Hct %, 95% CI 1.94-3.29). Trans men receiving testosterone esters had a larger increase in serum hematocrit levels compared to trans men receiving testosterone undecanoate (Δ 0.8 Hct %). Of 192 trans men, 22 (11.5%) developed serum hematocrit levels ≥50.0%. Trans men on testosterone undecanoate were less likely to develop hematocrit levels ≥50% or ≥52%, compared to trans men on testosterone esters, and were less likely to develop hematocrit levels ≥50%, compared to trans men on testosterone gel. In trans women, serum hematocrit had dropped by 4.1 Hct % (95% CI 3.50-4.37) after 3 months, after which only small decreases were observed. In conclusion, serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender-affirming hormonal treatment.
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Aside from the three prospective studies, data were extracted from medical charts (nine of which were from the same research group), posing a risk of selective data reporting and publication bias.
“Aside from these three studies, data were extracted from medical charts (nine of which were from the same research group,15 17 19 36–41) posing a risk of selective data reporting and publication bias.”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [19]
The Methods (page unavailable) identify this paper as a multicenter prospective cohort study with scheduled follow-up visits and blood sampling, not a study based on data extracted from medical charts. The Discussion (page unavailable) likewise calls it a prospective study. This paper therefore does not support classifying it among the chart-based studies; it does not assess the claimed count of nine or publication-bias risk across those studies. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThree large ENIGI studies published in 2018 and 2019 contained much novel data, but also included many participants from previous studies, making it impossible to accurately state the number of unique participants.
“Three large studies from the ENIGI group published in 2018 and 201915 17 19 contained much novel data, but also included many participants from previous studies making it impossible to accurately state the number of unique participants.”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [19]
The Methods and Results (page numbers unavailable) identify this as a large ENIGI study and report its analyzed participant counts. The Discussion describes a novel comparison. Our copy does not establish that participants overlapped with previous studies or that the number of unique participants across the three studies cannot be determined. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe large ENIGI study was the only study in which the limits of agreement would indicate a change in Hgb/HCT at the 95% CI.
“The large ENIGI study19 was the only study in which the limits of agreement would indicate a change in Hgb/HCT at the 95% CI.”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [19]
The Results (page unavailable) report a change in hematocrit in trans men with a 95% confidence interval. The paper does not report limits of agreement or establish that ENIGI was the only study meeting such a criterion; it also does not provide a corresponding hemoglobin result. (LLM, conf=0.85)
Experimental — accuracy not yet measuredNine studies reported Hgb or HCT levels in transwomen before and after GAHT, with follow-up from a minimum of 3 to a maximum of 36 months post hormone therapy.
“Nine studies16 19 36–38 43 47–49 reported the levels of Hgb or HCT in transwomen before and after GAHT, from a minimum of three to a maximum of 36 months post hormone therapy.”
Eight of the nine studies found that hormone therapy led to a significant decrease in Hgb/HCT of 4.6%-14.0% (p<0.01).
“Eight of these studies,16 19 36–38 43 48 49 including the large (n=239) ENIGI study,19 found that hormone therapy led to a significant (4.6%–14.0%) decrease in Hgb/HCT (p<0.01)”
In six of the eight other studies, mean testosterone after GAHT was less than 2.0 nmol/L.
“while in six16 19 36 37 43 48 of the eight other studies mean testosterone after GAHT was less than 2.0 nmol/L.”
After 3-4 months on GAHT, HCT or Hgb levels of transwomen match those of cisgender women.
“After 3–4 months on GAHT, the HCT19 or Hgb16 levels of transwomen matched those of cisgender women”
Hormone-naive transwomen and cisgender men have similar testosterone levels.
“hormone-naive transwomen and cisgender men have similar testosterone levels.16 17 19 42”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [19]
The Results (page unavailable) report testosterone levels in trans women after three months of treatment, but do not give a pretreatment level or compare hormone-naive trans women with cisgender men. Searches for baseline testosterone and male reference ranges did not locate that comparison in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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Hormone Therapy in Transgender Men
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The Transgender: Endocrinological Assessment
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- Authors
- Defreyne, J., Vantomme, B., Van Caenegem, E., Wierckx, K., De Blok, C. J. M., Klaver, M., Nota, N. M., Van Dijk, D., Wiepjes, C. M., Den Heijer, M., & T'Sjoen, G.
- Affiliations
- Ghent University Hospital (BE)
- Department of Endocrinology Ghent University Hospital Ghent Belgium
- Department of Endocrinology and Center of Expertise on Gender Dysphoria VU University Medical Center Amsterdam The Netherlands
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Defreyne, J.
- Venue
- Andrology
- Publisher
- Wiley
- Published
- 2018-03-30
- Volume
- 6
- Issue
- 3
- Pages
- 446-454
- ISSN
- 2047-2919 (ISSN-L)
- 2047-2927
- OpenAlex
- W2794831176
- Cited by
- 114
- References
- 44
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 14 · 2023: 17 · 2022: 19 · 2021: 16 · 2020: 13 · 2019: 8 · 2018: 2
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Andrology (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek (FWO TBM T001816N)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Social Sciences › Psychology › Social Psychology › LGBTQ Health, Identity, and Policy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- hematocrit, gender-affirming hormone therapy, transgender men, transgender women, testosterone esters, testosterone undecanoate, testosterone gel, reference values
- MeSH terms
- Adult, Androgen Antagonists, Estradiol, Europe, Female, Hematocrit, Humans, Male, Prospective Studies, Reference Values, Testosterone, Cohort Studies, Cyproterone Acetate, Gender-Affirming Procedures, Transgender Persons
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