Effect of Extended 30 μg Ethinyl Estradiol with Continuous Low-Dose Ethinyl Estradiol and Cyclic 20 μg Ethinyl Estradiol Oral Contraception on Adolescent Bone Density: A Randomized Trial.
OBJECTIVE
To compare changes in lumbar spine bone mineral density after 12 months of a 91-day extended regimen or 28-day combined oral contraceptive with those in a healthy reference group not using hormonal contraceptives.


METHODS
Phase 2, multicenter, open-label, randomized, controlled study.


METHODS
Forty-five academic centers, clinical research centers, and community practices in the United States.


METHODS
Eight hundred twenty-nine postmenarcheal adolescent girls aged 12-18 years.


METHODS
Adolescents were randomly assigned to 91-day levonorgestrel (LNG)/ethinyl estradiol (EE) extended regimen (84 days of LNG 150 μg/EE 30 μg with 7 days of EE 10 μg [LNG/EE extended regimen]) or 28 days of LNG/EE (21 days of LNG 100 μg/EE 20 μg with 7 days of placebo [LNG/EE 21/7]) for 12 months. A reference group not seeking hormonal contraception was also evaluated.


METHODS
The primary end point was mean percent change in lumbar spine bone mineral density measured using dual-energy x-ray absorptiometry.


RESULTS
Of 1361 adolescents randomized/enrolled, 829 were included in the primary analysis. Mean changes in lumbar spine bone mineral density were +2.26% with LNG/EE extended regimen, +1.45% with LNG/EE 21/7, and +2.50% in the reference group. Noninferiority of the LNG/EE extended regimen compared with the reference group was shown. A statistically significant treatment difference was found between LNG/EE 21/7 and the reference group (1.05%; 95% confidence interval, 0.61%-1.49%) but not between LNG/EE extended regimen and the reference group (0.23%; 95% confidence interval, -0.20% to 0.67%). No new safety signals were noted.


CONCLUSIONS
Compared with the reference group, bone accrual was statistically significantly lower among LNG/EE 21/7 users but not among LNG/EE 30-μg extended regimen users. Additional research is needed to clarify the clinical relevance of these findings.
New Age Medical Research Corporation, Miami, Florida. Electronic address: jkgersten@gmail.com.
Janet
J
Gersten
Teva Branded Pharmaceutical Products R&D, Inc, West Chester, Pennsylvania.
Jennifer
J
Hsieh
Teva Global Medical Affairs, Petach Tikva, Israel.
Herman
H
Weiss
Teva Branded Pharmaceutical Products R&D, Inc, Frazer, Pennsylvania.
Nancy A
NA
Ricciotti
D015502:Absorptiometry, Photon; D000293:Adolescent; D015519:Bone Density / Q000187:drug effects*; D002648:Child; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects
D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel
Adolescent; Bone density; Bone development; Combined hormonal contraceptive; Ethinyl estradiol; Levonorgestrel; Oral contraceptive