Bone accretion in adolescents using the combined estrogen and progestin transdermal contraceptive method Ortho Evra: a pilot study.
OBJECTIVE
To date, there are no data regarding the effect of the transdermal combined estrogen and progestin contraceptive Ortho Evra on bone mineral content (BMC) and bone mineral density (BMD). We examined the effects of transdermally delivered ethinyl estradiol and norelgestromin on whole body (WB) BMC and BMD of the hip and lumbar spine (LS) of adolescent girls.


METHODS
In a matched case-control study, girls (n = 5) who applied Ortho Evra for days 1-21 followed by days 22-28 free of medication for 13 cycles (about 12 months) were compared with 5 age- and ethnicity-matched control girls. Evaluations of calcium intake; bone-protective physical activity; bone densitometry (DXA, QDR 4500A, Hologic); bone formation markers serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP); bone resorption marker urinary N-telopeptide (uNTX); insulin growth factor-1 (IGF-1); and sex hormone binding globulin (SHBG) were carried out at initiation, 6 months, and 12 months. Changes from baseline were compared using mixed models, adjusting for follow-up comparisons using the Holm Test (sequential Bonferroni).


RESULTS
There were no significant differences (SD) between groups at baseline in age, gynecologic age, WBBMC, hip BMD, and LSBMD. Girls on Ortho Evra did not change significantly in WBBMC (12-month mean increase 0.2% +/- 0.8%), whereas controls did (3.9% +/- 1.8%, P < or = .001, adjusted P = .002), with SD between the 2 groups (P = .007, adjusted P = .036). Adolescents on Ortho Evra did not change significantly in hip BMD (12-month mean increase 0.5% +/- 0.6%), whereas controls did (2.7% +/- 0.6%, P < or = .001, adjusted P = .004), with SD between the 2 groups (P = .024) prior to adjustment for multiple comparisons, but no SD after adjustment (P = .096). Similarly, although the increase in LSBMD within the control group after 12 months (mean increase 2.8% +/- 1.0%) was statistically significant (P = .009, adjusted P = .044), the change within the treatment group (12-month mean increase 0.8% +/- 0.8%) was not. However, percent LSBMD changes after 12 months did not significantly differ between the 2 groups before or after adjustment for multiple comparisons. Calcium intake and bone-protective physical activity did not significantly predict BMC and BMD changes of study participants. There was a significantly greater increase in SHBG levels in the treatment group after 6 months (P = .003, adjusted P = .013) and 12 months (P < or = .001, adjusted P < or = .001) than in controls. Changes in levels of OC, BAP, uNTX, and IGF-1 were not significantly different between the 2 groups.


CONCLUSIONS
Ortho Evra use attenuates bone mass acquisition in young women who are still undergoing skeletal maturation. This attenuation may be attributed in part to increased SHBG levels, which reduce the concentrations of free estradiol and free testosterone that are available to interact with receptors on the bone. Clinical implications remain to be determined in studies with a larger number of adolescents.
Harel
Zeev
Z
Division of Adolescent Medicine, Hasbro Children's Hospital, Providence, Rhode Island 02903, USA. Zharel@Lifespan.org
Riggs
Suzanne
S
Vaz
Rosalind
R
Flanagan
Patricia
P
Harel
Dalia
D
Machan
Jason T
JT
D000293:Adolescent; D041923:Adolescent Development / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density; D001846:Bone Development / Q000187:drug effects*; D016022:Case-Control Studies; D002648:Child; D024042:Collagen Type I / Q000652:urine; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000494:pharmacology; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000652:urine; D010865:Pilot Projects; D012738:Sex Hormone-Binding Globulin / Q000032:analysis / Q000187:drug effects; D055815:Young Adult
D024042:Collagen Type I; D003271:Contraceptive Agents, Female; D004338:Drug Combinations; C511292:Ortho Evra; D010455:Peptides; D012738:Sex Hormone-Binding Globulin; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D009644:Norgestrel; D004997:Ethinyl Estradiol; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase