Effects of a Triphasic Combination Oral Contraceptive Containing Norgestimate/Ethinyl Estradiol on Biochemical Markers of Bone Metabolism in Young Women with Osteopenia Secondary to Hypothalamic Amenorrhea

• Published in: The journal of clinical endocrinology and metabolism 2003-08, Vol.88 (8), p.3651-3656
• Main Authors: Grinspoon, S. K., Friedman, A. J., Miller, K. K., Lippman, J., Olson, W. H., Warren, M. P.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amenorrhea - complications; Amenorrhea - metabolism; Biomarkers; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone Diseases, Metabolic - drug therapy; Bone Diseases, Metabolic - etiology; Bone Diseases, Metabolic - metabolism; Bone Resorption - metabolism; Cognition - drug effects; Contraceptives, Oral, Combined - adverse effects; Contraceptives, Oral, Combined - therapeutic use; Double-Blind Method; Ethinyl Estradiol - adverse effects; Ethinyl Estradiol - therapeutic use; Female; Gonadal Steroid Hormones - blood; Humans; Hypothalamic Diseases - complications; Hypothalamic Diseases - metabolism; Norgestrel - adverse effects; Norgestrel - analogs & derivatives; Norgestrel - therapeutic use
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-030033

This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180–250 μg of norgestimate (NGM) and 35 μg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age ± sd, 26.5 ± 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (sd), −13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [−1.2 (2.9) vs. −0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [−5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [−5.9 (3.6) vs. −2.9 (3.7); P = 0.016], and procollagen of type I propeptide [−35.2 (44.6) vs. −0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. −0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [−3.7 (3.8) vs. −0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population.