We appreciate the interest that Drs Aznar and Cerdá have expressed in our Clinical Opinion piece. We did not intend to minimize the importance of factor V Leiden as a risk factor for venous thromboembolism (VTE) in women taking combined oral contraceptives (COCs). However, we primarily addressed the risks of myocardial infarction (MI) and ischemic stroke (IS), which are arterial thrombotic events, with COCs. Accordingly, we cited some well-established risk factors for MI and IS, and we suggested that tools such as the Framingham risk calculator may be helpful adjuncts to American College of Obstetricians and Gynecologists (ACOG) and World Health Organization (WHO) guidelines by allowing physicians to estimate the attributable risk of COC-related cardiovascular events such as MI and coronary death.

Regardless, the correspondence from Drs Aznar and Cerdá raises an important but controversial issue: factor V Leiden may possibly be associated with an increased risk of arterial thrombosis. However, available data are mixed, and any increase in arterial thrombosis risk (if present) is likely modest at worst, in contrast to VTE risks, which appear to be substantially higher. Furthermore, it remains unclear precisely how factor V Leiden influences COC-related risks of MI and IS; for example, the apparent risks of COC-associated MI were not influenced by factor V Leiden in 1 study. For these reasons, our current opinion is that factor V Leiden cannot be reliably incorporated into formal risk assessments for arterial thrombosis in those taking COCs.

Dr Aznar suggested that, based on a previous analysis of VTE risks, screening for factor V Leiden before COC use is reasonable in women with a personal or family history of VTE. We agree with WHO and ACOG guidelines that COCs should be avoided in women at high risk for COC-related VTE (eg, personal history of VTE, known thrombophilia). Of interest, the WHO guidelines suggest that a family history of VTE is not generally a contraindication to COC use, and neither guideline endorses routine screening for factor V Leiden. Although we cannot fully engage this controversial topic herein, we respectfully offer the following comment: because reducing the risk of unwanted pregnancy can at least partially offset the risks of VTE with COCs, screening for factor V Leiden in subjects at intermediate risk of VTE (eg, a history of VTE in a first-degree relative) may be more easily justified when using COCs for noncontraceptive indications, especially those associated with subfertility.