title: Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence.
abstract: BACKGROUND
  The aim was to evaluate changes of bone mineral density (BMD) and markers of bone turnover in healthy adolescents, and in adolescent users of combined oral contraceptives (COCs) with different ethinylestradiol (EE) contents.
  
  
  METHODS
  In this prospective crossover study, 56 healthy females (15-19.5 years) with desire to use hormonal contraception were randomized to COC with either 30 or 15 μg of EE in crossover design of 9-month intervention each in reverse order. Nonusers of the same age (n=28) served as controls. BMD at lumbar spine (LS), total femur, femoral neck, distal radius, and total body, and serum markers (N-propeptide of type I procollagen, and type I collagen C-telopeptide) were measured at baseline and after 9 and 18 months.
  
  
  RESULTS
  In COC nonusers, BMD significantly increased at LS and radius, while markers decreased. In COC users, BMD did not increase, with the exception of LS BMD in the 30 μg COC group (P<0.05). In the crossover design, a difference between the low- and very low-dose COC users was found in LS BMD changes (P<0.05), where increase in BMD was more impaired in the 15 μg COC users. The skeletal effects of COC remained significant after adjustments for age and smoking status. Markers declined faster in COC users during the first period, while they remained stable or even increased during the second 9 months.
  
  
  CONCLUSIONS
  Physiological acquisition of LS BMD during adolescent age may be prevented by use of COC, especially those containing very low dose of EE.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine 1, Charles University, Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Cibula
authors.forename: Jana
authors.initials: J
authors.lastname: Skrenkova
authors.forename: Martin
authors.initials: M
authors.lastname: Hill
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Stepan
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D015986:Confounding Factors, Epidemiologic; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects*; D018592:Cross-Over Studies; D003720:Densitometry; D004334:Drug Administration Schedule; D004563:Electrochemistry; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005269:Femur / Q000378:metabolism; D005272:Femur Neck / Q000378:metabolism; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008159:Lumbar Vertebrae / Q000378:metabolism; D049449:Luminescence; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D011884:Radius / Q000378:metabolism; D012107:Research Design; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D003277:Contraceptives, Oral, Combined; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D014807:Vitamin D; D004997:Ethinyl Estradiol; C104450:25-hydroxyvitamin D