Original article
Effects of an Oral Contraceptive (Norgestimate/Ethinyl Estradiol) on Bone Mineral Density in Adolescent Females with Anorexia Nervosa: A Double-Blind, Placebo-Controlled Study

https://doi.org/10.1016/j.jadohealth.2006.09.010Get rights and content

Abstract

Purpose

To evaluate the effect of an oral contraceptive (OC) on bone mineral density (BMD) in adolescent females with anorexia nervosa (AN) or eating disorder not otherwise specified (EDNOS).

Methods

Females 11–17 years of age with AN or EDNOS entered the study. Subjects were randomized equally to treatment with a triphasic OC containing norgestimate (NGM) 180–250 μg and ethinyl estradiol (EE) 35 μg or placebo for 13 28-day cycles. Dual energy x-ray absorptiometry scans (DXA) of the lumbosacral spine (LS) and hip were obtained at baseline and after 6 and 13 cycles.

Results

Demographic characteristics of the 112 subjects (NGM/EE 53; Placebo 59) who received study drug and had at least one on-treatment DXA were similar between groups for age (mean: 15 years in each group) and body mass index (mean: NGM/EE 17.9 kg/m2; Placebo 17.6 kg/m2). At the end of Cycle 6, there was a significant increase in the mean LS BMD in the NGM/EE group compared with placebo (.020 g/cm2 vs. .008 g/cm2; p = .021); however, at the end of Cycle 13 the mean increase in LS BMD in the NGM/EE group compared with placebo was no longer significant (.026 g/cm2 vs. .019 g/cm2, p = .244). There was no significant difference in change in hip BMD between groups. The incidence of adverse events was similar between groups.

Conclusions

In a group of adolescent females with AN or EDNOS, treatment with a triphasic OC for 13 cycles did not have a statistically significant effect on LS or hip BMD.

Section snippets

Study population

This study was conducted from September 2002 to April 2004 at 43 investigative sites in the United States. Eligible subjects were adolescent females 11 to 17 years of age with a diagnosis of AN made by the investigator before or at the time of enrollment based on modified DSM-IV guidelines. The modification was in the weight criterion as suggested by Hebebrand et al [23]; the < 85% ideal body weight (IBW) criterion was replaced by an age-adjusted body mass index (BMI) of < 10th percentile [24].

Enrollment and retention of subjects

Of 146 subjects randomized, 23 were screen failures, 123 received at least one dose of study medication (61 NGM/EE; 62 placebo), and 112 had one on-treatment DXA (Figure 1). The majority of discontinuations from treatment were due to “subject choice” (11 NGM/EE; six placebo). Four subjects were withdrawn from the study due to adverse events: three (4.9%) in the NGM/EE group (nausea, weight increase, and menstrual disorder [irregular periods]) and one (1.6%) in the placebo group (headache and

Discussion

After 13 cycles of treatment with a triphasic OC, adolescent females with AN or EDNOS had no statistically significant improvement in LS or hip BMD compared with placebo-treated subjects. A statistically significant increase in LS BMD in OC-treated subjects compared with placebo subjects was observed at the end of six cycles for the total group but the difference did not reach statistical significance for the AN subgroup. Increases in LS and femoral neck BMD were in the 1.5% to 2.5% range after

Acknowledgments

The authors thank the investigators (Paul Ambrosini, M.D.; Louise Beckett, M.D.; Scott Crow, M.D.; Robert Dahmes, M.D.; James Ferguson, M.D.; Ken Fujioka, M.D.; Janet Gersten, M.D.; Peter Gleason, M.D.; Neville Golden, M.D.; Cynthia Guy, M.D.; Katherine Halmi, M.D.; Mazen Hamad, M.D.; Lisa Harris, M.D., Madelon Hartford, M.D.; Craig Johnson, M.D.; James Lee, M.D.; Mark Lerman, M.D.; Michael Levy, M.D.; Robert Littman, M.D.; Stephen Luber, M.D.; Richard Jaffe, M.D.; Madhusmita Misra, M.D.;

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