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).


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


METHODS
Thirty-seven centers in five European countries.


METHODS
Parous or nulliparous women aged 21-40 years.


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


METHODS
Pearl index, bleeding profile, ease/pain of placement/removal, adverse events.


RESULTS
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.


CONCLUSIONS
LNG-IUS12 and LNG-IUS16 provided effective contraception, acceptable bleeding patterns, and were well tolerated compared with Mirena.
Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden. kristina.gemzell@ki.se
Kristina
K
Gemzell-Danielsson
Ilka
I
Schellschmidt
Dan
D
Apter
D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005060:Europe; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects; D008598:Menstruation / Q000187:drug effects*; D011247:Pregnancy; D049168:Pregnancy, Unplanned; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D003280:Contraceptives, Oral, Synthetic; D016912:Levonorgestrel