Hormone-related venous thromboembolism (VTE) is common and entails scenarios in which VTE occurs during exposure to exogenous or endogenous female sex hormones, typically estrogen and progestogen. For the management of hormone-related VTE, it is important to realize that many patients use these hormones for a vital purpose often strongly related to the patient's well-being and quality of life. In this review we discuss clinical cases of VTE related to hormonal contraceptive use and pregnancy to illustrate key considerations for clinical practice. We cover practice points for primary VTE treatment and detail the evidence on the risk of recurrent VTE and bleeding in this population. The potential value of thrombophilia testing is described, including “who, why, when, what, and how.” We also discuss key aspects of shared decision-making for anticoagulant duration, including a reduced-dose anticoagulant strategy in hormone-related VTE.

1.
Bistervels
IM
,
Scheres
LJJ
,
Hamulyák
EN
,
Middeldorp
S.
Sex matters: practice 5P's when treating young women with venous thromboembolism
.
J Thromb Haemost
.
2019
;
17
(
9
):
1417
-
1429
.
2.
van Hylckama Vlieg
A
,
Helmerhorst
FM
,
Vandenbroucke
JP
,
Doggen
CJM
,
Rosendaal
FR
.
The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study
.
BMJ
.
13
August
2009
;
339
(
2
):
b2921
.
3.
Scheres
LJJ
,
Bistervels
IM
,
Middeldorp
S.
Everything the clinician needs to know about evidence-based anticoagulation in pregnancy
.
Blood Rev
.
January
2019
;
33
:
82
-
97
.
4.
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
.
5.
Samuelson Bannow
B
,
McLintock
C
,
James
P.
Menstruation, anticoagulation, and contraception: VTE and uterine bleeding
.
Res Pract Thromb Haemost
.
2021
;
5
(
5
):
e12570
.
6.
Scheres
L
,
Brekelmans
M
,
Ageno
W
, et al.
Abnormal vaginal bleeding in women of reproductive age treated with edoxaban or warfarin for venous thromboembolism: a post hoc analysis of the Hokusai-VTE study
.
BJOG
.
2018
;
125
(
12
):
1581
-
1589
.
7.
Brekelmans
MP
,
Scheres
LJ
,
Bleker
SM
, et al.
Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin
.
Thromb Haemost
.
2017
;
117
(
4
):
809
-
815
.
8.
Jong
CM de
,
Blondon
M
,
Ay
C
, et al.
Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism
.
Blood
.
2022
;
140
(
16
):
1764
1773
.
9.
Patel
JP
,
Nzelu
O
,
Roberts
LN
,
Johns
J
,
Ross
J
,
Arya
R.
How do anticoagulants impact menstrual bleeding and quality of life? The PERIOD study
.
Res Pract Thromb Haemost
.
2023
;
7
(
2
):
100072
.
10.
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
.
11.
Verlaan
JPL
,
Stegeman
BH
,
Timp
JF
, et al.
Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women
.
J Thromb Haemost
.
2024
;
22
(
8
):
2195
-
2202
.
12.
Brill-Edwards
P
,
Ginsberg
JS
,
Gent
M
, et al.
Safety of withholding heparin in pregnant women with a history of venous thromboembolism
.
N Engl J Med
.
2000
;
343
(
20
):
1439
1444
.
13.
Pabinger
I
,
Grafenhofer
H
,
Kaider
A
, et al.
Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis
.
J Thromb Haemost
.
2005
;
3
(
5
):
949
-
954
.
14.
James
AH
,
Jamison
MG
,
Brancazio
LR
,
Myers
ER
.
Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality
.
Am J Obstet Gynecol
.
2006
;
194
(
5
):
1311
-
1315
.
15.
De Stefano
V
,
Martinelli
I
,
Rossi
E
, et al.
The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis
.
Br J Haematol
.
2006
;
135
(
3
):
386
-
391
.
16.
White
RH
,
Chan
WS
,
Zhou
H
,
Ginsberg
JS
.
Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism
.
Thromb Haemost
.
2008
;
100
(
2
):
246
-
252
.
17.
Lazo-Langner
A
,
Al-Ani
F
,
Weisz
S
, et al.
Prevention of venous thromboembolism in pregnant patients with a history of venous thromboembolic disease: a retrospective cohort study
.
Thromb Res
.
July
2018
;
167
:
20
-
25
.
18.
Bates
SM
,
Rajasekhar
A
,
Middeldorp
S
, et al.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy
.
Blood Adv
.
2018
;
2
(
22
):
3317
-
3359
.
19.
Bistervels
IM
,
Buchmüller
A
,
Wiegers
HMG
, et al
;
Highlow Block Writing Committee; Highlow Investigators
.
Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open- label, multicentre, randomised, controlled trial
.
Lancet
.
2022
;
400
(
10365
):
1777
-
1787
.
20.
Baglin
T
,
Luddington
R
,
Brown
K
,
Baglin
C.
Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study
.
Lancet
.
2003
;
362
(
9383
):
523
-
526
.
21.
Scheres
LJJ
,
Lijfering
WM
,
Cannegieter
SC
.
Current and future burden of venous thrombosis: not simply predictable
.
Res Pract Thromb Haemost
.
2018
;
2
(
2
):
199
-
208
.
22.
Konstantinides
SV
,
Meyer
G
,
Becattini
C
, et al
;
ESC Scientific Document Group
.
2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)
.
Eur Heart J
.
2020
;
41
(
4
):
543
-
603
.
23.
Winter
MA de
,
Es
N van
,
Büller
HR
,
Visseren
FLJ
,
Nijkeuter
M.
Prediction models for recurrence and bleeding in patients with venous thromboembolism: a systematic review and critical appraisal
.
Thromb Res
.
March
2021
;
199
:
85
-
96
.
24.
Burggraaf
JLI
,
van Rein
N
,
Klok
FA
,
Cannegieter
SC
.
How to predict recurrent venous thromboembolism and bleeding? A review of recent advances and their implications
.
Pol Arch Intern Med
.
2023
;
133
(
5
):
16492
.
25.
Wiegers
HMG
,
Knijp
J
,
Es
N van
, et al.
Risk of recurrence in women with venous thromboembolism related to estrogen-containing contraceptives: systematic review and meta-analysis
.
J Thromb Haemost
.
2022
;
20
(
5
):
1158
-
1165
.
26.
Abdulrehman
J
,
Elbaz
C
,
Aziz
D
, et al.
Recurrence after stopping anticoagulants in women with combined oral contraceptive-associated venous thromboembolism: a systematic review and meta-analysis
.
Br J Haematol
.
2022
;
199
(
1
):
130
-
142
.
27.
Middeldorp
S
,
Nieuwlaat
R
,
Baumann Kreuziger
L
, et al.
American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing
.
Blood Adv
.
2023
;
7
(
22
):
7101
-
7138
.
28.
Agnelli
G
,
Buller
HR
,
Cohen
A
, et al
;
AMPLIFY-EXT Investigators
.
Apixaban for extended treatment of venous thromboembolism
.
N Engl J Med
.
2013
;
368
(
8
):
699
-
708
.
29.
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
.
30.
Mantha
S
,
Karp
R
,
Raghavan
V
,
Terrin
N
,
Bauer
KA
,
Zwicker
JI
.
Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis
.
BMJ
.
7
August
2012
;
345
:
e4944
.
31.
Lidegaard
O
,
Nielsen
LH
,
Skovlund
CW
,
Løkkegaard
E.
Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10
.
BMJ
.
May
2012
;
344
:
e2990
.
32.
Lidegaard
Ø
,
Nielsen
LH
,
Skovlund
CW
,
Skjeldestad
FE
,
Løkkegaard
E.
Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9
.
BMJ
.
October
2011
;
343
:
d6423
.
33.
Poulter
NR
,
Chang
CL
,
Farley
TM
,
Meirik
O.
Risk of cardiovascular diseases associated with oral progestagen preparations with therapeutic indications
.
Lancet
.
1999
;
354
(
9190
):
1610
.
34.
LaVasseur
C
,
Neukam
S
,
Kartika
T
,
Samuelson Bannow
B
,
Shatzel
J
,
DeLoughery
TG
.
Hormonal therapies and venous thrombosis: considerations for prevention and management
.
Res Pract Thromb Haemost
.
2022
;
6
(
6
):
e12763
.
35.
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
.
36.
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
.
37.
Douketis
J
,
Tosetto
A
,
Marcucci
M
, et al.
Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis
.
BMJ
.
24
February
2011
;
342
:
d813
.
38.
Iorio
A
,
Kearon
C
,
Filippucci
E
, et al.
Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review
.
Arch Intern Med
.
2010
;
170
(
19
):
1710
-
1716
.
39.
Khan
F
,
Tritschler
T
,
Kimpton
M
, et al
;
MAJESTIC Collaborators
.
Long-term risk for major bleeding during extended oral anticoagulant therapy for first unprovoked venous thromboembolism: a systematic review and meta-analysis
.
Ann Intern Med
.
2021
;
174
(
10
):
1420
-
1429
.
40.
Khan
F
,
Rahman
A
,
Tritschler
T
, et al.
Long-term risk of major bleeding after discontinuing anticoagulation for unprovoked venous thromboembolism: a systematic review and meta-analysis
.
Thromb Haemost
.
2022
;
122
(
7
):
1186
-
1197
.
41.
Favaloro
EJ
,
Pasalic
L
,
Selby
R.
Testing for the lupus anticoagulant: the good, the bad, and the ugly
.
Res Pract Thromb Haemost
.
2024
;
8
(
3
):
102385
.
42.
Devreese
KMJ
,
de Groot
PG
,
de Laat
B
, et al.
Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: update of the guidelines for lupus anticoagulant detection and interpretation
.
J Thromb Haemost
.
2020
;
18
(
11
):
2828
-
2839
.
43.
Barbhaiya
M
,
Zuily
S
,
Naden
R
, et al
;
ACR/EULAR APS Classification Criteria Collaborators
.
2023 ACR/EULAR antiphospholipid syndrome classification criteria
.
Ann Rheum Dis
.
2023
;
82
(
10
):
1258
-
1270
.
You do not currently have access to this content.