The risk of cerebral vein thrombosis associated with different types of combined hormonal contraceptives: a case-control study

Background: Cerebral vein thrombosis (CVT) is a rare manifestation of venous thrombosis predominantly affecting women due to female-specific risk factors, such as combined hormonal contraceptive (CHC) use. However, limited data exist on how different CHC types affect CVT risk. Objectives: This study aimed to evaluate CVT risk across CHC types and to investigate their combined effects with thrombophilia, family history of thrombosis, and body mass index. Methods: This case-control study included women with CVT (cases) and healthy women (controls) of childbearing age who were referred to our Center from 1992 to 2019 for a thrombophilia work-up. Women with pregnancy- and cancer-related CVT were excluded. Results: In total, 206 cases (157 CHC users, 49 nonusers) and 868 controls (196 CHC users, 672 nonusers) were included. CHC users had a 10-fold higher risk of CVT (odds ratio [OR]: 10.9; 95% CI: 7.7-15.7) than nonusers. Higher estrogen doses increased the risk in a dose-response manner. Variable estrogen dose CHC carried a 6-fold increased risk, similar to progestin-only pills. The risk increased with fourth-generation pills (OR: 28.3; 95% CI: 14.6-54.9). Thrombophilia abnormalities had a synergistic effect with CHC use (OR: 67.8; 95% CI: 34.6-133.0). For CHC users with a positive family history of thrombosis, the OR of the combined effect varied from 47.0 (95% CI: 24.4-90.7) to 254.1 (95% CI: 79.8-809.0), depending on the absence or presence of thrombophilia abnormalities. Conclusion: This study underscores the complex interaction between CHC type and other thrombotic risk factors in influencing CVT risk among women of childbearing age.