Oral Contraceptives and Neutropenia: A Population-Based Cohort Study

Background: Oral contraceptives (OCs) are one of the most commonly used classes of drugs worldwide. A case of neutropenia and associated infections in a young woman using OCs that settled after discontinuation and reappeared upon re-challenge, has led us to investigate a potential association between oral contraceptives and neutropenia. Objectives: To compare rates of neutropenia among women receiving OCs to a matched control group of women not exposed to the “pill”. Patients and Methods: In this population-based cohort study we used a large computerized database of a health fund, comparing women prescribed OCs and a control group not using the pill. We selected a cohort of 51,394 OC users aged 16–40 years who purchased their first monthly pack of OCs between 2010 and 2018. Controls included all non-pregnant women aged 16–40 years for whom OC was not dispensed (n = 140,932). Neutrophil count before and during OC were compared. Results: Prior to OC exposure, 1.3% of the women were neutropenic, compared to 1.6% after exposure to OC (RR 1.22; 95% CI 1.1–1.35). Mean neutrophil count changed from 3.87 × 10³ to 3.82 × 10³ mm³ (p < 0.001). In the control group (n = 140,932) no difference was seen in the proportion of neutropenic women between the first complete blood count (1.7%) compared to the second (1.8%) count (p = 0.305). In all severity levels, neutropenia was significantly more common in the OC group. The relative risk was higher for severe (RR 1.63) than for mild neutropenia (RR 1.13) (p = 0.034 for trend). Conclusions: There is a significant increase in the proportion of neutropenic women after initiating OCs. More research is needed in order to evaluate the effect of neutropenia in this group of women.