Thyroid function, activated protein C resistance and the risk of venous thrombosis in users of hormonal contraceptives.
BACKGROUND
Use of combined hormonal contraceptives is associated with a three- to eight-fold increased risk of venous thrombosis compared with non-use. The thrombotic risk depends on the estrogen dose as well as the progestogen type. Use of hormonal contraceptives leads to resistance to activated protein C (APC), which may serve as marker for the risk of venous thrombosis. Hyperthyroidism is also associated with an increased risk of venous thrombosis, due to increased free Thyroxine (FT4) levels which cause a hypercoagulable state.


METHODS
The objective of this study was to evaluate the effects of hormonal contraceptives on levels of FT4, thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG), and to investigate the effects on APC resistance per contraceptive group. We measured FT4, TBG and TSH levels and APC resistance in 231 users of oral contraceptives.


RESULTS
Users of the most thrombogenic hormonal contraceptives, i.e. containing desogestrel, cyproterone acetate or drospirenone, had higher TBG levels than users of less thrombogenic hormonal contraceptives, i.e. the levonorgestrel-containing intrauterine device. TSH levels were not significantly elevated and FT4 levels did not change. TBG levels were also associated with APC resistance.


CONCLUSIONS
Use of hormonal contraceptives lead to elevated TBG levels, slightly elevated TSH levels and unchanged FT4 levels without causing a hyperthyroid state. Thus, the increased thrombotic risk during the use of hormonal contraceptives cannot be explained by a hyperthyroid state caused by use of these hormonal contraceptives.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: m.raps@lumc.nl.
M
M
Raps
Department of Chemistry, Catharina Hospital, Eindhoven, the Netherlands.
J
J
Curvers
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Reproductive Medicine, Leiden University Medical Center, Leiden, the Netherlands.
F M
FM
Helmerhorst
Department of Chemistry, Leiden University Medical Center, Leiden, The Netherlands.
B E P B
BE
Ballieux
Department of Biochemistry, Maastricht University, Maastricht, the Netherlands.
J
J
Rosing
Department of Biochemistry, Maastricht University, Maastricht, the Netherlands.
S
S
Thomassen
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
F R
FR
Rosendaal
Department of Gynaecology, Catharina Hospital, Eindhoven, the Netherlands.
H A A M
HA
van Vliet
D020016:Activated Protein C Resistance / Q000097:blood / Q000139:chemically induced*; D000293:Adolescent; D000328:Adult; D003274:Contraceptive Devices, Female; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007435:Intrauterine Devices, Copper / Q000009:adverse effects; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013961:Thyroid Gland / Q000187:drug effects*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D056825:Thyroxine-Binding Globulin / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood / Q000139:chemically induced*; D055815:Young Adult
D003276:Contraceptives, Oral; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D056825:Thyroxine-Binding Globulin; D013972:Thyrotropin; D013974:Thyroxine