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 micro g of
norgestimate (NGM) and 35 microg 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.