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BACKGROUND Low concentrations of leptin secondary to low body fat or other modulators are thought to be a key signal whereby an energy deficit suppresses the reproductive axis in exercising women resulting in functional hypothalamic amenorrhea (FHA). The purpose of this study was to first examine leptin concentrations in exercising women with and without FHA to address whether there is a threshold concentration of leptin below which reproductive function is suppressed. Secondly, we examined the role of adiposity and other possible modulators of leptin to ascertain whether leptin regulation differs depending on reproductive status. METHODS This study assessed 50 exercising, premenopausal women (aged 18–30 years) over the course of one menstrual cycle (eumenorrheic women) or one 28-day monitoring period (amenorrheic women). Quantification of daily urinary ovarian steroids and menstrual history were used to determine menstrual status. Body composition was assessed using dual energy X-ray absorptiometry, and leptin was determined by enzyme-linked immunoassay. Key modulators of leptin such as serum insulin concentration, carbohydrate intake, glucose availability, indirect indices of sympathetic nervous activity and other factors were assessed using linear regression. RESULTS Percentage body fat (%BF) (21.0 ± 1.0 versus 26.8 ± 0.7%; P< 0.001) and leptin concentration (4.8 ± 0.8 versus 9.6 ± 0.9 ng/ml; P< 0.001) were lower in the exercising women with amenorrhea (ExAmen; n = 24) compared with the exercising ovulatory women (ExOvul; n= 26). However, the ranges in leptin were similar for each group (ExAmen: 0.30–16.98 ng/ml; ExOvul: 2.57–18.28 ng/ml), and after adjusting for adiposity the difference in leptin concentration was no longer significant. Significant predictors of log leptin in ExAmen included %BF (β = 0.826, P< 0.001), log insulin (β = 0.308, P= 0.012) and log glycerol (β = 0.258, P= 0.030), but in ExOvul only %BF predicted leptin. CONCLUSIONS These data suggest that leptin concentrations per se are not associated with FHA in exercising women, but the modulation of leptin concentrations may differ depending on reproductive status. [ABSTRACT FROM AUTHOR]

Abstract: Background: In women with anorexia nervosa, elevated fasting peptide YY (PYY) is associated with decreased bone mineral density (BMD). Prior research from our lab has demonstrated that fasting total PYY concentrations are elevated in exercising women with amenorrhea compared to ovulatory exercising women. Purpose: The purpose of this study was to assess the association between fasting total PYY, average monthly estrogen exposure and BMD in non-obese premenopausal exercising women. Methods: Daily urine samples were collected and assessed for metabolites of estrone 1-glucuronide (E1G) and pregnandiol glucuronide (PdG) for at least one menstrual cycle if ovulatory or a 28-day monitoring period if amenorrheic. Fasting serum samples were pooled over the measurement period and analyzed for total PYY and leptin. BMD and body composition were assessed by dual-energy X-ray absorptiometry. Multiple regression analyses were performed to determine whether measures of body composition, estrogen status, exercise minutes, leptin and PYY explained a significant amount of the variance in BMD at multiple sites. Results: Premenopausal exercising women aged 23.8±0.9years with a mean BMI of 21.2±0.4kg/m2 exercised 346±48min/week and had a peak oxygen uptake of 49.1±1.8mL/kg/min. Thirty-nine percent (17/44) of the women had amenorrhea. Fasting total PYY concentrations were negatively associated with total body BMD (p=0.033) and total hip BMD (p=0.043). Mean E1G concentrations were positively associated with total body BMD (p=0.033) and lumbar spine (L2–L4) BMD (p=0.047). The proportion of variance in lumbar spine (L2–L4) BMD explained by body weight and E1G cycle mean was 16.4% (R2 =0.204, p=0.012). The proportion of variance in hip BMD explained by PYY cycle mean was 8.6% (R2 =0.109, p=0.033). The proportion of variance in total body BMD explained by body weight and E1G cycle mean was 21.9% (R2 =0.257, p=0.003). Conclusion: PYY, mean E1G and body weight are associated with BMD in premenopausal exercising women. Thus, elevated PYY and suppressed estrogen concentrations are associated with, and could be directly contributing to, low BMD in exercising women with amenorrhea, despite regular physical activity. [Copyright &y& Elsevier]