NuvaRing does not affect bone mineral density in pre-menopausal women
R. Massai (1), L. Mäkäräinen (2), A. Kuukankorpi (3), C. Klipping (4), I.
Duijkers (4), T. Dieben (5)
Instituto Chileno de Medicina Reproductiva, Santiago, Chile (1);
Department of Obstetrics and Gynaecology, University of Oulu, Finland (2);
Family Planning Clinic, Tampere, Finland (3); Dinox Medical Investigations,
Nijmegen, The Netherlands (4); Clinical Development Department, NV Organon, Oss,
The Netherlands (5)
Introduction: In pre-menopausal women, hormonal contraceptives have
been associated with positive, neutral and even negative effects on bone mineral
density (BMD), differences that may be dose-dependent and/or age related in
nature. NuvaRing is a monthly combined contraceptive vaginal ring that releases
15 µg ethinylestradiol and 120 µg etonogestrel daily and has been shown to be
effective, well tolerated, convenient and highly acceptable to users. The
objective of this trial was to compare the effects of NuvaRing and non-hormonal
methods or no contraception on BMD in pre-menopausal women.
Design and methods: This was an open-label, multicentre trial in
healthy women (n=144; 18–35 years). Subjects were assigned 3:1 to NuvaRing
(n=105) and control groups (n=39). The control group consisted of women who did
not use a contraceptive method, those who chose to use or were already using a
non-hormonal intrauterine device (IUD), and those who wished to use a
non-hormonal contraceptive method other than the IUD. The NuvaRing group was
treated for 26 cycles, each of 4 weeks’ duration (3 weeks’ ring use, 1 week
ring-free), and the control group was treated for 24 months. Assessments of BMD
of the lumbar spine and proximal femur were made using dual-energy X-ray after
cycles 13 (month 12) and 26 (month 24).
Results: Of the 142 treated subjects, 27 in the NuvaRing group (26.2%)
and eight in the control group (20.5%) discontinued. The reasons for
discontinuation in the NuvaRing group were adverse events (15.5%) and ‘other
reasons’ (10.7%), such as a desire to become pregnant. In the control group,
two women using IUDs discontinued due to pregnancy (5.1%), two due to adverse
events (5.1%) and four for ‘other reasons’ (10.3%). No change in BMD was
observed in NuvaRing users (n=93) in the lumbar spine (Z-score change: 70.058
and 70.098) or femoral neck (70.057 and 70.061) from baseline to cycle 13 or 26,
respectively. In the control group (n=34), BMD increased slightly in both the
lumbar spine (0.212 and 0.257) and the femoral neck (0.085 and 0.223). The
between-group differences were statistically significant for the lumbar spine at
cycle 13/month 12 (p=0.003) and for both the lumbar spine and femoral neck at
cycle 26/month 24 (both p<0.0001). These differences were not considered clinically relevant. NuvaRing was generally well tolerated and no notable treatment differences in body weight were observed between the two groups.
Conclusions: Two years of NuvaRing use in healthy adult women had no
effect on BMD.
