A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena.

OBJECTIVE

To identify an appropriate dose for a new contraceptive levonorgestrel intrauterine system (LNG-IUS).

DESIGN

Randomized, open-label, three-arm, phase II study.

SETTING

Thirty-seven centers in five European countries.

PATIENT(S): Parous or nulliparous women aged 21-40 years.

INTERVENTION(S): Treatment with LNG-IUSs with initial in vitro release rates of 12 or 16 μg/d (LNG-IUS12/16) or 20 μg/d (Mirena).

MAIN OUTCOME MEASURE(S): Pearl index, bleeding profile, ease/pain of placement/removal, adverse events.

RESULT(S): A total of 738 subjects had an LNG-IUS placed (LNG-IUS12, n = 239; LNG-IUS16, n = 245; Mirena, n = 254). One, 5, and 0 pregnancies occurred in the LNG-IUS12, LNG-IUS16, and Mirena groups, respectively (3-year unadjusted Pearl indices: 0.17, 0.82, and 0). The bleeding profiles were similar in all groups, although total bleeding and spotting days decreased with increasing LNG dose. During 3 years, 10 subjects in the LNG-IUS12 (2 women), LNG-IUS16 (3 women), and Mirena (5 women) groups reported serious adverse events, possibly related to study treatment. Placement of LNG-IUS12 and LNG-IUS16 was considered easy in 94% versus 86.2% in the Mirena group and 72.3% in the LNG-IUS12/LNG-IUS16 group reported either "no pain" or only "mild pain" during placement versus 57.9% in the Mirena group.

CONCLUSION(S): LNG-IUS12 and LNG-IUS16 provided effective contraception, acceptable bleeding patterns, and were well tolerated compared with Mirena.