This paper was accepted for publication in the journal Bone and the definitive published version is available at: http://dx.doi.org/10.1016/j.bone.2010.12.018BACKGROUND: The role of adiponectin in mediating gonadal status and bone health in weight-stable healthy adult female athletes with secondary amenorrhea has not yet been described. METHODS: Using a prospective observational study, age-matched premenopausal women were studied, including 1) sedentary ovulatory women (SedOv; n=10), 2) exercising ovulatory women (ExOv; n=15), and 3) exercising amenorrheic women (ExAmen; n=9). Primary outcome measures included serum total adiponectin and daily urinary estrogen (E1G) levels, expressed as area under the curve (AUC), body fat distribution, and bone mineral density (BMD). Serum leptin, ghrelin, total triiodothyronine (TT3), insulin, and resting energy expenditure (REE) were also determined. RESULTS: The women in this study did not differ in age (25.3±1.4 years; mean ± SEM), height (164±1 cm), weight (57.7±1.0 kg) and BMI (21.5±0.4 kg/m(2)). Exercising women had a higher fat free mass (FFM), lower fat mass (FM) and lower serum leptin concentrations (p<0.05) compared to sedentary women. Adiponectin and ghrelin levels were higher (p<0.05), and TT3 (p=0.019), urinary E1G AUC (p=0.002) lower in ExAmen compared with ExOv and SedOv. Total and L1-L4 BMD were lower (p<0.05) in ExAmen compared with ExOv. Stepwise linear regression identified trunkal FM as the strongest predictor of log adiponectin adjusted for FM (F=23.54, p<0.001). L1-L4 BMD was predicted by log adiponectin and E1G AUC (F=9.856, p=0.045). Total BMD was predicted by log adiponectin (F=7.948, p=0.009). TT3 was the strongest predictor of E1G AUC (F=9.885, p=0.004). CONCLUSIONS: Hypoestrogenic adult female athletes with secondary amenorrhea demonstrate elevated circulating adiponectin relative to FM in association with impaired bone health. Estrogen exposure was predicted by TT3, but not adiponectin. These findings suggest that nutritionally regulated hormones may mediate gonadal status, and that adiponectin and estrogen, either independently or in combination, may mediate bone health in adult amenorrheic physically active women
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