Research regarding the hematologic sequelae of estrogen and testosterone therapy for transgender people is an emerging area. While estrogen therapy has been widely studied in cisgender women, studies in transgender individuals are limited, revealing variable adverse effects influenced by the dose and formulation of estrogen used. Thrombotic risk factors in transgender and gender-diverse individuals are multifactorial, involving both modifiable and nonmodifiable factors. Management of venous thromboembolism (VTE) in individuals receiving gender-affirming estrogen entails standard anticoagulation therapy alongside shared decision-making regarding hormone continuation and risk factor modification. While data and guidance from cisgender women can offer a reference for managing thrombotic risk in transgender individuals on hormone therapy, fully applying these insights can be challenging. The benefits of gender-affirming hormone therapy include significantly reducing the risk of suicide and depression, highlighting the importance of a contemplative approach to the management of hormonal therapy after a VTE event. Although limited, the available data in the literature indicate a low thrombotic risk for transgender individuals undergoing gender-affirming testosterone therapy. However, polycythemia is a common adverse effect necessitating monitoring and, occasionally, adjustments to hormonal therapy. Additionally, iron deficiency may arise due to the physiological effects of testosterone or health care providers' use of phlebotomy, an aspect that remains unstudied in this population. In conclusion, while the set of clinical data is expanding, further research remains vital to refine management strategies and improve hematologic outcomes for transgender individuals undergoing gender-affirming hormone therapy.

1.
Coleman
E
,
Radix
AE
,
Bouman
WP
, et al.
Standards of care for the health of transgender and gender diverse people, version 8
.
Int J Transgend Health
.
2022
;
23
(
suppl 1
):
S1
-
S259
.
2.
Green
AE
,
DeChants
JP
,
Price
MN
,
Davis
CK
.
Association of gender-affirming hormone therapy with depression, thoughts of suicide, and attempted suicide among transgender and nonbinary youth
.
J Adolesc Health
.
2022
;
70
(
4
):
643
-
649
.
3.
Wierckx
K
,
Mueller
S
,
Weyers
S
, et al.
Long-term evaluation of cross-sex hormone treatment in transsexual persons
.
J Sex Med
.
2012
;
9
(
10
):
2641
-
2651
.
4.
Zucker
R
,
Reisman
T
,
Safer
JD
.
Minimizing venous thromboembolism in feminizing hormone therapy: applying lessons from cisgender women and previous data
.
Endocr Pract
.
2021
;
27
(
6
):
621
-
625
.
5.
Scheres
LJJ
,
Selier
NLD
,
Nota
NM
,
van Diemen
JJK
,
Cannegieter
SC
,
den Heijer
M.
Effect of gender-affirming hormone use on coagulation profiles in transmen and transwomen
.
J Thromb Haemost
.
2021
;
19
(
4
):
1029
-
1037
.
6.
Getahun
D
,
Nash
R
,
Flanders
WD
, et al.
Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study
.
Ann Intern Med
.
2018
;
169
(
4
):
205
-
213
.
7.
Oger
E
,
Alhenc-Gelas
M
,
Lacut
K
, et al
;
SARAH Investigators
.
Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopAUsal women: a randomized trial
.
Arterioscler Thromb Vasc Biol
.
2003
;
23
(
9
):
1671
-
1676
.
8.
Zöller
B.
Genetics of venous thromboembolism revised
.
Blood
.
2019
;
134
(
19
):
1568
-
1570
.
9.
Canonico
M
,
Oger
E
,
Plu-BureAU
G
, et al
;
Estrogen and Thromboembolism Risk (ESTHER) Study Group
.
Hormone therapy and venous thromboembolism among postmenopAUsal women: impact of the route of estrogen administration and progestogens: the ESTHER study
.
Circulation
.
2007
;
115
(
7
):
840
-
845
.
10.
Hembree
WC
,
Cohen-Kettenis
PT
,
Gooren
L
, et al.
Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline
.
J Clin Endocrinol Metab
.
2017
;
102
(
11
):
3869
-
3903
.
11.
Totaro
M
,
Palazzi
S
,
Castellini
C
, et al.
Risk of venous thromboembolism in transgender people undergoing hormone feminizing therapy: a prevalence meta-analysis and meta-regression study
.
Front Endocrinol (LAUsanne)
.
2021
;
12
:
741866
.
12.
Nelson
HD
,
Humphrey
LL
,
Nygren
P
,
Teutsch
SM
,
Allan
JD
.
PostmenopAUsal hormone replacement therapy: scientific review
.
JAMA
.
2002
;
288
(
7
):
872
-
881
.
13.
Hoibraaten
E
,
Qvigstad
E
,
Arnesen
H
,
Larsen
S
,
Wickstrom
E
,
Sandset
PM
.
Increased risk of recurrent venous thromboembolism during hormone replacement therapy—results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET)
.
Thromb Haemost
.
2000
;
84
(
6
):
961
-
967
.
14.
Bonnar
J.
Coagulation effects of oral contraception
.
Am J Obstet Gynecol
.
1987
;
157
(
4
):
1042
-
1048
.
15.
Pyra
M
,
Casimiro
I
,
Rusie
L
, et al.
An observational study of hypertension and thromboembolism among transgender patients using gender-affirming hormone therapy
.
Transgend Health
.
2020
;
5
(
1
):
1
-
9
.
16.
Liu
B.
Is transdermal menopAUsal hormone therapy a safer option than oral therapy?
CMAJ
.
2013
;
185
(
7
):
549
-
550
.
17.
Sandset
PM
,
Høibraaten
E
,
Eilertsen
AL
,
Dahm
A.
Mechanisms of thrombosis related to hormone therapy
.
Thromb Res
.
2009
;
123
(
suppl 2
):
S70
-
S73
.
18.
Asscheman
H
,
Giltay
EJ
,
Megens
JAJ
,
de Ronde
WP
,
van Trotsenburg
MAA
,
Gooren
LJG
.
A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones
.
Eur J Endocrinol
.
2011
;
164
(
4
):
635
-
642
.
19.
Olié
V
,
Canonico
M
,
Scarabin
P-Y
.
Risk of venous thrombosis with oral versus transdermal estrogen therapy among postmenopAUsal women
.
Curr Opin Hematol
.
2010
;
17
(
5
):
457
-
463
.
20.
Lutsey
PL
,
Steffen
LM
,
Virnig
BA
,
Folsom
AR
.
Diet and incident venous thromboembolism: the Iowa Women's Health Study
.
Am Heart J
.
2009
;
157
(
6
):
1081
-
1087
.
21.
Pomp
ER
,
Rosendaal
FR
,
Doggen
CJ
.
Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use
.
Am J Hematol
.
2008
;
83
(
2
):
97
-
102
.
22.
Spyridoula
M
,
Singh Ospina
N
,
Rodriguez-Gutierrez
R
, et al.
Sex steroids and cardiovascular outcomes in transgender individuals: a systematic review and meta-analysis
,
J Clin Endocrinol Metab
2017
;
102
(
11
):
3914
-
3923
.
23.
Vickers
MR
,
MacLennan
AH
,
Lawton
B
, et al
;
WISDOM group
.
Main morbidities recorded in the Women's International Study of Long Duration Oestrogen After MenopAUse (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopAUsal women
.
BMJ
.
2007
;
335
(
7613
):
239
.
24.
Rossouw
JE
,
Anderson
GL
,
Prentice
RL
, et al
;
Writing Group for the Women's Health Initiative Investigators
.
Risks and benefits of estrogen plus progestin in healthy postmenopAUsal women: principal results from the Women's Health Initiative randomized controlled trial
.
JAMA
.
2002
;
288
(
3
):
321
-
333
.
25.
Manchkanti
S
,
Dayal
S
,
Ramakrishna
A
,
Streeter
J.
Transgender women on estrogen have a lower burden of thrombotic events compared to cisgender men: a nationwide hospital-based survey
.
Blood
.
2023
;
142
(
suppl 1
):
1282
.
26.
Polderman
KH
,
Stehouwer
CD
,
van Kamp
GJ
,
Dekker
GA
,
Verheugt
FW
,
Gooren
LJ
.
Influence of sex hormones on plasma endothelin levels
.
Ann Intern Med
.
1993
;
118
(
6
):
429
-
432
.
27.
Weitz
JI
,
Lensing
AWA
,
Prins
MH
, et al
;
EINSTEIN CHOICE Investigators
.
Rivaroxaban or aspirin for extended treatment of venous thromboembolism
.
N Engl J Med
.
2017
;
376
(
13
):
1211
-
1222
.
28.
Asscheman
H
,
Gooren
LJG
,
Eklund
PLE
.
Mortality and morbidity in transsexual patients with cross-gender hormone treatment
.
Metabolism
.
1989
;
38
(
9
):
869
-
873
.
29.
Arnold
JD
,
Sarkodie
EP
,
Coleman
ME
,
Goldstein
DA
.
Incidence of venous thromboembolism in transgender women receiving oral estradiol
.
J Sex Med
.
2016
;
13
(
11
):
1773
-
1777
.
30.
Ott J
,
KA
Ufmann
U
,
Bentz
E-K
,
Huber
J-C
,
Tempfer
C-B
.
Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy
.
Fertil Steril
.
2010
;
93
(
4
):
1267
-
1272
.
31.
Vinogradova
Y
,
Coupland
C
,
Hippisley-Cox
J.
Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases
.
BMJ
.
2019
;
364
:
k4810
.
32.
Marjoribanks
J
,
Farquhar
C
,
Roberts
H
,
Lethaby
A
,
Lee
J.
Long-term hormone therapy for perimenopAUsal and postmenopAUsal women
.
Cochrane Database Syst Rev
.
2017
;
1
(
1
):
CD004143
.
33.
Nolan
BJ
,
Cheung
AS
.
Relationship between serum estradiol concentrations and clinical outcomes in transgender individuals undergoing feminizing hormone therapy: a narrative review
.
Transgend Health
.
2021
;
6
(
3
):
125
-
131
.
34.
Key
NS
,
Khorana
AA
,
Kuderer
NM
, et al.
Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update
.
J Clin Oncol
.
2020
;
38
(
5
):
496
-
520
.
35.
Lyman
GH
,
Carrier
M
,
Ay
C
, et al.
American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer
.
Blood Adv
.
2021
;
5
(
4
):
927
-
974
.
36.
Seidu
S
,
Kunutsor
SK
,
Sesso
HD
, et al.
Aspirin has potential benefits for primary prevention of cardiovascular outcomes in diabetes: updated literature-based and individual participant data meta-analyses of randomized controlled trials
.
Cardiovasc Diabetol
.
2019
;
18
(
1
):
70
.
37.
Gelles-Soto
D
,
Ward
D
,
Florio
T
,
Kouzounis
K
,
Salgado
CJ
.
Maximizing surgical outcomes with gender affirming hormone therapy in gender affirmation surgery
.
J Clin Transl Endocrinol
.
2024
;
36
:
100355
.
38.
Hontscharuk
R
,
Alba
B
,
Manno
C
, et al.
Perioperative transgender hormone management: avoiding venous thromboembolism and other complications
.
Plast Reconstr Surg
.
2021
;
147
(
4
):
1008
-
1017
.
39.
Lawrence
AA
.
Patient-reported complications and functional outcomes of male-to-female sex reassignment surgery
.
Arch Sex Behav
.
2006
;
35
(
6
):
717
-
727
.
40.
Arrington-Sanders
R
,
Connell
NT
,
Coon
D
, et al.
Assessing and addressing the risk of venous thromboembolism across the spectrum of gender affirming care: a review
.
Endocr Pract
.
2023
;
29
(
4
):
272
-
278
.
41.
Kozato
A
,
Fox
GWC
,
Yong
PC
, et al.
No venous thromboembolism increase among transgender female patients remaining on estrogen for gender-affirming surgery
.
J Clin Endocrinol Metab
.
2021
;
106
(
4
):
e1586
-
e1590
.
42.
Boskey
ER
,
Taghinia
AH
,
Ganor
O.
Association of surgical risk with exogenous hormone use in transgender patients: a systematic review
.
JAMA Surg
.
2019
;
154
(
2
):
159
-
169
.
43.
Haveles
CS
,
Wang
MM
,
Arjun
A
,
Zaila
KE
,
Lee
JC
.
Effect of cross-sex hormone therapy on venous thromboembolism risk in male-to-female gender-affirming surgery
.
Ann Plast Surg
.
2021
;
86
(
1
):
109
-
114
.
44.
Cronin
M
,
Dengler
N
,
KrAUss
ES
, et al.
Completion of the updated caprini risk assessment model (2013 Version)
.
Clin Appl Thromb Hemost
.
2019
;
25
:
1076029619838052
.
45.
Ortel
TL
,
Neumann
I
,
Ageno
W
, et al.
American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism
.
Blood Adv
.
2020
;
4
(
19
):
4693
-
4738
.
46.
Witt
DM
,
Nieuwlaat
R
,
Clark
NP
, et al.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy
.
Blood Adv
.
2018
;
2
(
22
):
3257
-
3291
.
47.
Martinelli
I
,
Lensing
AW
,
Middeldorp
S
, et al.
Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use
.
Blood
.
2016
;
127
(
11
):
1417
-
1425
.
48.
Mullins
ES
,
Geer
R
,
Metcalf
M
, et al.
Thrombosis risk in transgender adolescents receiving gender-affirming hormone therapy
.
Pediatrics
.
2021
;
147
(
4
):
e2020023549
.
49.
Oakes
M
,
Arastu
A
,
Kato
C
, et al.
Erythrocytosis and thromboembolic events in transgender individuals receiving gender-affirming testosterone
.
Thromb Res
.
2021
;
207
:
96
-
98
.
50.
Nota
NM
,
Wiepjes
CM
,
de Blok
CJM
,
Gooren
LJG
,
Kreukels
BPC
,
den Heijer
M.
Occurrence of acute cardiovascular events in transgender individuals receiving hormone therapy
.
Circulation
.
2019
;
139
(
11
):
1461
-
1462
.
51.
Madsen
MC
,
van Dijk
D
,
Wiepjes
CM
,
Conemans
EB
,
Thijs
A
,
den Heijer
M.
Erythrocytosis in a large cohort of trans men using testosterone: a long-term follow-up study on prevalence, determinants, and exposure years
.
J Clin Endocrinol Metab
.
2021
;
106
(
6
):
1710
-
1717
.
52.
Tatarian
J
,
Walcott
Q
,
Richardson
K.
Incidence, contributing factors, and implications for clinical management of polycythemia in transmasculine patients on testosterone
.
LGBT Health
.
2023
;
10
(
1
):
72
-
79
.
53.
Cannarella
R
,
Gusmano
C
,
Leanza
C
, et al.
Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis
.
Asian J Androl
.
2024
;
26
(
2
):
144
-
154
.
54.
Houghton
DE
,
Alsawas
M
,
Barrioneuvo
P
, et al.
Testosterone therapy and venous thromboembolism: a systematic review and meta-analysis
.
Thromb Res
.
Dec
2018
;
172
:
94
-
103
.
55.
Walker
RF
,
Zakai
NA
,
MacLehose
RF
, et al.
Association of testosterone therapy with risk of venous thromboembolism among men with and without hypogonadism
.
JAMA Intern Med
.
2020
;
180
(
2
):
190
-
197
.
56.
Glueck
CJ
,
Richardson-Royer
C
,
Schultz
R
, et al.
Testosterone therapy, thrombophilia-hypofibrinolysis, and hospitalization for deep venous thrombosis-pulmonary embolus: an exploratory, hypothesis-generating study
.
Clin Appl Thromb Hemost
.
2014
;
20
(
3
):
244
-
249
.
57.
Freedman
J
,
Glueck
CJ
,
Prince
M
,
Riaz
R
,
Wang
P.
Testosterone, thrombophilia, thrombosis
.
Transl Res
.
2015
;
165
(
5
):
537
-
548
.
58.
Coviello
AD
,
Kaplan
B
,
Lakshman
KM
,
Chen
T
,
Singh
AB
,
Bhasin
S.
Effects of graded doses of testosterone on erythropoiesis in healthy young and older men
.
J Clin Endocrinol Metab
.
2008
;
93
(
3
):
914
-
919
.
59.
Nadeem
O
,
Gui
J
,
Ornstein
DL
.
Prevalence of venous thromboembolism in patients with secondary polycythemia
.
Clin Appl Thromb Hemost
.
2013
;
19
(
4
):
363
-
366
.
60.
Ayele
HT
,
Brunetti
VC
,
Renoux
C
,
Tagalakis
V
,
Filion
KB
.
Testosterone replacement therapy and the risk of venous thromboembolism: a systematic review and meta-analysis of randomized controlled trials
.
Thromb Res
.
2021
;
199
:
123
-
131
.
61.
Jones
SD
, Jr.
,
Dukovac
T
,
Sangkum
P
,
Yafi
FA
,
Hellstrom
WJ
.
Erythrocytosis and polycythemia secondary to testosterone replacement therapy in the aging male
.
Sex Med Rev
.
2015
;
3
(
2
):
101
-
112
.
62.
Martinez
C
,
Suissa
S
,
Rietbrock
S
, et al.
Testosterone treatment and risk of venous thromboembolism: population based case-control study
.
BMJ
.
2016
;
355
:
i5968
.
63.
Bhasin
S
,
Brito
JP
,
Cunningham
GR
, et al.
Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline
.
J Clin Endocrinol Metab
.
2018
;
103
(
5
):
1715
-
1744
.
64.
Mulhall
JP
,
Trost
LW
,
Brannigan
RE
, et al.
Evaluation and management of testosterone deficiency: AUA guideline
.
J Urol
.
2018
;
200
(
2
):
423
-
432
.
65.
Dobs
AS
,
Meikle
AW
,
Arver
S
,
Sanders
SW
,
Caramelli
KE
,
Mazer
NA
.
Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men
.
J Clin Endocrinol Metab
.
1999
;
84
(
10
):
3469
-
3478
.
66.
Gangat
N
,
Szuber
N
,
Tefferi
A.
JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management
.
Am J Hematol
.
2023
;
98
(
6
):
965
-
981
.
67.
Bachman
E
,
Travison
TG
,
Basaria
S
, et al.
Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point
.
J Gerontol: Series A
.
2014
;
69
(
6
):
725
-
735
.
68.
Bachman
E
,
Feng
R
,
Travison
T
, et al.
Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis
.
J Clin Endocrinol Metab
.
2010
;
95
(
10
):
4743
-
4747
.
69.
Lutsey
PL
,
Zakai
NA
.
Epidemiology and prevention of venous thromboembolism
.
Nat Rev Cardiol
.
2023
;
20
(
4
):
248
-
262
.
70.
Connelly
PJ
,
Marie Freel
E
,
Perry
C
, et al.
Gender-affirming hormone therapy, vascular health and cardiovascular disease in transgender adults
.
Hypertension
.
2019
;
74
(
6
):
1266
-
1274
.
71.
Seal
LJ
,
Franklin
S
,
Richards
C
,
Shishkareva
A
,
Sinclaire
C
,
Barrett
J.
Predictive markers for mammoplasty and a comparison of side effect profiles in transwomen taking various hormonal regimens
.
J Clin Endocrinol Metab
.
2012
;
97
(
12
):
4422
-
4428
.
72.
van Kesteren
PJ
,
Asscheman
H
,
Megens
JA
,
Gooren
LJ
.
Mortality and morbidity in transsexual subjects treated with cross-sex hormones
.
Clin Endocrinol (Oxf)
.
1997
;
47
(
3
):
337
-
342
.
73.
Weller
SC
,
Davis
JW
,
Porterfield
L
,
Chen
L
,
Wilkinson
G.
Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years
.
Res Pract Thromb Haemost
.
2023
;
7
(
3
):
100135
.
74.
Grady
D
,
Applegate
W
,
Bush
T
,
Furberg
C
,
Riggs
B
,
Hulley
SB
.
Heart and estrogen/progestin replacement study (HERS): design, methods, and baseline characteristics
.
Control Clin Trials
.
1998
;
19
(
4
):
314
-
335
.
75.
Porat
AT
,
Ellwood
M
,
Rodina
M
,
Dianat
S.
Erythrocytosis in gender-affirming care with testosterone
.
Ann Fam Med
.
2023
;
21
(
5
):
403
-
407
.
76.
T'Sjoen
G
,
Arcelus
J
,
De Vries
ALC
, et al.
European Society for Sexual Medicine Position Statement “Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction”
.
J Sex Med
.
2020
;
17
(
4
):
570
-
584
.
77.
Dinger
J
,
Do Minh
T
,
Heinemann
K.
Impact of estrogen type on cardiovascular safety of combined oral contraceptives
.
Contraception
.
2016
;
94
(
4
):
328
-
339
.
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