Background: The monophasic hormonal combined oral contraceptive (COC) ethinylestradiol (EE) 0.03 mg/chlormadinone acetate (CMA) 2 mg (Belara®) has been shown to have good long-term efficacy and tolerability.

Objectives: The aim of this study was to corroborate the long-term safety of EE 0.03 mg/CMA 2 mg by evaluating the incidence and severity of adverse drug reactions (ADRs) and cycle control over 13 treatment cycles. Additionally, the influence of EE 0.03 mg/CMA 2 mg on dysmenorrhoea, acne and the well-being of subjects was also investigated.

Methods: This observational study was conducted in Spain, France and Italy from April 2006 to August 2008. Subjects of reproductive age, without contraindications mentioned in the current summary of product characteristics, were prescribed EE 0.03 mg/CMA 2 mg in routine clinical practice.

Results: 3771 subjects were analysed and at least one ADR was reported in 833 (22.1%) subjects, with the majority of ADRs (75.6%) being judged as mild or moderate. The most frequently reported ADRs were intermenstrual bleeding (7.7% of all analysed subjects), headache (5.1%) and breast pain (2.7%). Spotting and breakthrough bleeding (defined as slight and heavier intermenstrual bleeding) at baseline were reported by 677 (18.0%) and 268 (7.1%) subjects, but were less frequent in cycles 10-13 (9.6% and 1.7%, respectively). Before study start, 61.8% of subjects suffered from dysmenorrhea, with the intensity being moderate or severe in 66.9% of these subjects. In cycles 10-13, the corresponding values were noted in 15.0% and 25.6% of subjects. The proportion of subjects who suffered from acne decreased from 46.5% at study entry to 14.9% after 13 medication cycles. More than 50% of the subjects who had switched from another oral contraceptive (OC) pill stated that the tolerability of EE 0.03 mg/CMA 2 mg and their health-related well-being were much better or better after two cycles of EE 0.03 mg/CMA 2 mg than when they were taking their previous OC, and about 85% of the subjects assessed the tolerability of EE 0.03 mg/CMA 2 mg as very good or good during the study.

Conclusion: These results re-affirmed the favourable ADR profile of the COC EE 0.03 mg/CMA 2 mg, as well as its good cycle control and beneficial effects on dysmenorrhoea, complaints typically occurring during the cycle, acne and well-being.