CONTEXT Lower bone density in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and non-athletes may increase fracture risk during a critical time of bone accrual. Finite element analysis (FEA) is a unique tool to estimate bone strength in vivo, and the contribution of cortical microstructure to bone strength in young athletes is not well understood. OBJECTIVE We hypothesized that FEA-estimated stiffness and failure load are impaired in AA at the distal radius and tibia compared to EA and non-athletes despite weight-bearing exercise. DESIGN AND SETTING Cross-sectional study; Clinical Research Center SUBJECTS 34 female endurance athletes involved in weight-bearing sports (17 AA, 17 EA) and 16 non-athletes (14-21y) of comparable age, maturity and BMI OUTCOME MEASURES We used HR-pQCT images to assess cortical microarchitecture and FEA to estimate bone stiffness and failure load. RESULTS Cortical perimeter, porosity and trabecular area at the weight-bearing tibia were greater in both groups of athletes than non-athletes, whereas the ratio (%) of cortical to total area was lowest in AA. Despite greater cortical porosity in EA, estimated tibial stiffness and failure load was higher than in non-athletes. However, this advantage was lost in AA. At the non-weight-bearing radius, failure load and stiffness were lower in AA than non-athletes. After controlling for lean mass and menarchal age, athletic status accounted for 5-9% of the variability in stiffness and failure load, menarchal age for 8-23%, and lean mass for 12-37%. CONCLUSION AA have lower FEA-estimated bone strength at the distal radius than non-athletes, and lose the advantage of weight-bearing exercise seen in EA at the distal tibia.

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.

Objective-Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers (AE) from eumenorrhoeic exercisers (EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and non-exercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. Design-Cross-sectionalSubjects-We studied 21 AE, 18 EE and 20 non-exercisers 14-21 years (BMI 10th-90 th %iles).Measurements-Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation (P1NP) and bone resorption (CTX) marker were measured.Results-BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve (AUC) were highest in AE (p=0.04, 0.007, 0.04 and 0.003) and were associated inversely with fat mass (r=−0.29, −0.28 and −0.35, p=0.03, 0.04 and 0.007). We observed inverse associations between cortisol and LH AUC (r= −0.36, p=0.008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1NP in non-exercisers.Conclusions-Higher cortisol secretion in AE compared with EE and non-exercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol.