Background

Oral contraceptives (OCs) are a very popular and efficacious form of reversible birth control. The pill’s efficacy plus it’s convenience gives women both autonomy and flexibility in family planning. This played no small role in the major social movements of the 1960s and 1970s.

The first OCs introduced in the early 1960s contained high doses of estrogens and progestin by today's standards. The estrogen doses (150 mcg mestranol and 50 mcg ethinylestradiol, respectively) were quickly associated with an elevated incidence of cardiovascular side effects, especially venous thromboembolism (VTE).

During the following decades the estrogen as well as progestin doses were considerably reduced. The scientific discussion on VTE shifted to the type of progestin in the mid-1990s. Epidemiological studies [1, 2, 3, 4] appeared to indicate that so-called third-generation progestins are linked with a higher risk of VTE. In subsequent years, a number of studies have been published with conflicting results. Whether the VTE risk associated with third-generation OCs is real or the result of bias and confounding has been the subject of heated scientific debate.

This debate, which has yet to be conclusively resolved [5, 6], is due to the fact that robust safety data that could either substantiate or refute a higher risk of VTE were not available at the time of the ‘pill scare’.

In order to avoid a comparable situation for the market introduction of an OC with a novel progestin (30mcg EE and 3mg drospirenone (DRSP) [7, 8, 9, 10, 11] the manufacturer commissioned the Center for Epidemiology and Health Research in Berlin to perform a large, prospective, controlled cohort study as part of a phase IV commitment. The safety of this DRSP-containing preparation was assessed using active surveillance of the study participants under the supervision of an independent Advisory Council.*1

The methodology and logistics of the study were designed to ensure that within a few years, the risks of short and long-term use of DRSP-containing OCs and established OCs could be characterized and compared in a study population that was representative of the users of the individual preparations.

The main clinical outcomes of interest were cardiovascular events, i.e. incidence rates of arrhythmias, myocardial infarction, stroke, venous thromboembolism, and sudden death. The primary variable was the VTE hazard ratio between users of EE/DRSP and users of LNG-containing OCs.

This publication presents the main safety outcomes of this European Active Surveillance (EURAS) study. Other results of the EURAS study (e.g., return to fertility and pearl index data) will be reported separately.

*1 The Advisory Council had the following members: Prof. Walter Spitzer (chairman), Canada; Ms. Midori Ashida, Japan (till 2002); Dr. Siham Benchekroun, Morocco (since 2002); Prof. Serge Carriere, Canada; Dr. Jean Cohen, France; Prof. Joe Goldzieher, USA (till 2002); Prof. Samuel Shapiro, USA/South Africa (till 2004); Sir Murray Stuart-Smith, United Kingdom.