peptide-yy and Amenorrhea

Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight-bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and nonathletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotropin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes.

Topics: Adipokines; Adolescent; Amenorrhea; Body Fat Distribution; Body Mass Index; Bone Density; Energy Metabolism; Female; Ghrelin; Gonadotropins; Humans; Menstrual Cycle; Osteogenesis; Peptide YY; Sports

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.. 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.. 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.. Premenopausal exercising women aged 23.8±0.9years with a mean BMI of 21.2±0.4kg/m(2) 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% (R(2)=0.204, p=0.012). The proportion of variance in hip BMD explained by PYY cycle mean was 8.6% (R(2)=0.109, p=0.033). The proportion of variance in total body BMD explained by body weight and E1G cycle mean was 21.9% (R(2)=0.257, p=0.003).. 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.

Topics: Absorptiometry, Photon; Adolescent; Adult; Amenorrhea; Bone Density; Estrogens; Estrone; Exercise; Fasting; Female; Humans; Leptin; Peptide YY; Pregnanediol; Premenopause; Young Adult

The purpose of this study was twofold: (1) to determine if gastrointestinal hormones, associated with energy intake and energy balance, are altered in exercising women with hypothalamic amenorrhea and (2) to assess the association between gastrointestinal hormones and behavioural indicators of subclinical disordered eating in exercising women with hypothalamic amenorrhea. This cross-sectional study analyzed serum ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), menstrual status (by E1G and PdG), resting energy expenditure (REE), and subclinical eating behaviours in sedentary ovulatory (SedOv), exercising ovulatory (ExOv), and exercising amenorrheic (ExAmen) women. Groups were similar with respect to age (23.8+/-0.6 years) and BMI (21.4+/-0.3 kg/m(2)). The ratio of REE to predicted REE (REE:predicted REE) was 0.94+/-0.02, 0.94+/-0.02, and 0.88+/-0.02 in the SedOv, ExOv, and ExAmen groups, respectively. The REE:predicted REE in the ExAmen group was consistent with an energy deficiency. LogPYY, ghrelin, dietary cognitive restraint, and drive for thinness were elevated in the ExAmen group compared to other groups. GLP-1 concentrations were similar among groups. LogPYY correlated with drive for thinness and REE/FFM. In conclusion, fasting PYY and ghrelin concentrations are elevated in exercising women with FHA and both gastrointestinal peptides may serve as a proxy indicator of energy deficiency in this population.

Topics: Adolescent; Adult; Amenorrhea; Body Mass Index; Cross-Sectional Studies; Energy Intake; Energy Metabolism; Exercise; Feeding and Eating Disorders; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Hypothalamus; Menstrual Cycle; Peptide YY; Thinness

Bone mineral density (BMD) is lower in amenorrheic athletes (AA) compared with eumenorrheic athletes (EA). Decreased energy availability and altered levels of appetite regulating hormones (ghrelin and leptin) in AA contribute to hypogonadism, an important cause of low BMD. The role of other nutritionally regulated hormones such as peptide YY (PYY) and adiponectin in mediating gonadal status and bone metabolism remains to be determined.. Our objective was to determine whether PYY and adiponectin are higher in AA compared with EA and contribute to hypogonadism and impaired bone metabolism in AA.. We determined PYY and adiponectin in 16 AA, 15 EA and 16 non-athletic controls 12-18 years old, and other nutritionally dependent hormones including ghrelin, leptin and IGF-1. We also measured testosterone, estradiol, PINP and NTX (markers of bone formation and resorption) and BMD.. PYY was higher in AA than EA (111+/-52 vs. 61+/-29 pg/ml, p<0.05), whereas adiponectin did not differ between groups. Although activity scores did not differ, BMI was lower in AA than EA and a larger proportion (62.5% vs. 6.7%) reported disordered eating, indicating lower energy availability. PYY and adiponectin were independent predictors of testosterone in a regression model (p=0.01 and 0.04), but did not predict estradiol. PYY, but not adiponectin, was an independent and negative predictor of PINP (p=0.002) and lumbar bone mineral apparent density Z-scores (p=0.045) in this model.. High PYY levels (but not adiponectin) differentiate AA from EA, and may be an important factor contributing to low bone density in athletes.

Topics: Adiponectin; Adolescent; Amenorrhea; Body Composition; Bone and Bones; Bone Density; Case-Control Studies; Child; Female; Humans; Ovary; Peptide YY; Regression Analysis; Sports; Steroids