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Abstract

Résumé La participation à une activité physique de loisir est largement reconnue pour offrir des avantages importants pour la santé. À l’inverse, un entraînement trop intensif génère de nombreux stress intermittents ou chroniques d’ordres métaboliques et psychologiques associés à un faible poids corporel pour maximiser les performances. Les adolescentes et les femmes sportives sont donc à risque de surentraînement et/ou de troubles du comportement alimentaire qui peuvent avoir plusieurs conséquences sur les fonctions endocriniennes et plus particulièrement sur l’axe hypothalamo-hypophyso-gonadique. Les athlètes féminines, en particulier celles qui participent aux sports nécessitant une silhouette mince et un faible poids corporel, présentent une forte prévalence de troubles du cycle avec des manifestations cliniques comme un retard de la ménarche, une oligoménorrhée et une aménorrhée primaire ou secondaire. Néanmoins, une forte variabilité de ces troubles est observée en fonction du type de sport et de l’intensité de la pratique. Durant l’adolescence, les troubles de la fonction de reproduction induite par l’exercice peuvent avoir des conséquences sur la vitesse de croissance, la maturation osseuse et sur l’acquisition de la masse osseuse, tandis que chez l’adulte, elles peuvent entraîner une réduction de la masse osseuse. Des données récentes soulignent le rôle important du tissu adipeux et du bilan énergétique dans la régulation de l’homéostasie et de la fonction de reproduction. Une meilleure compréhension des mécanismes par lesquels l’entraînement intensif affecte les systèmes endocriniens pourrait orienter les recherches pour le développement de stratégies novatrices, probablement fondées sur une approche nutritionnelle individualisée, pour améliorer la prise en charge médicale de ces athlètes féminines et de protéger ainsi leur fonction de reproduction.

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... Here, we propose a new continuous model validated on experimental data showing the interplay between the two types of cells at the origin of bone remodeling, namely osteoblasts and osteoclasts. The model was developed in parallel with experiments made on running whistar rats to predict BMD evolution for different running activity intensity as previously shown [7,8]. The proposed model contains only four parameters that were evaluated from experimental data. ...
Presentation
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For many years, bone mineral density (BMD) evolution was numerically predicted based on the classical assumption that it is directly dependent on the intensity of the mechanical energy developed with the material. However, with new mechanobiological comprehension of the mechanisms at the origin of this evolution [1], this idea is slowly fading away lately as it is becoming more and more evident that biological activity, although being dependent on the mechanical forces, is the main driving parameter of the BMD distribution. Models were lately developed trying to fill this gap [2-4], but transposing the local cellular activity at the organ scale remains challenging [5, 6]. Here, we propose a new continuous model validated on experimental data showing the interplay between the two types of cells at the origin of bone remodeling, namely osteoblasts and osteoclasts. The model was developed in parallel with experiments made on running whistar rats to predict BMD evolution for different running activity intensity as previously shown [7, 8]. The proposed model contains only four parameters that were evaluated from experimental data. A geometry of rat tibia was modeled within the software Comsol Multiphysics ®. The theoretical model was used to predict the variation of BMD as a function of time for different intensity of mechanical loads. We show that for medium intermediate running activity, the BMD increases whereas for higher continuous running activity, the BMD is decreasing. We also show that BMD evolution is dependent on the evolution of the porosity within the bone both experimentally and numerically. Overall average predicted BMD as a function of time is also correlated with experiments. Foreseen developments are the prediction of optimum activity for sport training or bone recovery through physical activity after injury.
... In the present work, we describe the bone remodelling phenomenon at a macroscopic scale based on a direct relation between the mechanical strain and the cellular activity. Our main objective is to show that reverse effects (Zhang and Zheng 2011;Maïmoun et al. 2016) of the mechanical strains on bone mineral density can be modeled, more precisely that a decrease of the bone density as a function of the cellular activity can be due to the overloading of the structure. ...
Conference Paper
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In the last century, most of the bone remodelling models available in the literature were based on mechanical strain energy and the interdependence between the bone mineral density and the applied mechanical loads. More recently, trying to optimize the knowledge of the links between the mechanical forces and the biological reactions (Stoltz et al. 2018), a number of mechanobiological models were developed (George et al. 2018, 2019). Some models try to take into account the bone cells activity both at the local (Lemaire et al. 2011) and at the global (Frame et al. 2018) scales. However, bridging between these two scales remains challenging (Sheidaei et al. 2019; Bagherian et al. 2020). The next step in bone remodelling is to integrate biological processes that are at the origin of the bone tissue evolutions such as the capillary growth (Bednarczyk and Lekszycki 2016), the nutrients supply, or the cells migration (Allena and Maini 2014). In the present work, we describe the bone remodelling phenomenon at a macroscopic scale based on a direct relation between the mechanical strain and the cellular activity. Our main objective is to show that reverse effects (Zhang and Zheng 2011; Maïmoun et al. 2016) of the mechanical strains on bone mineral density can be modeled, more precisely that a decrease of the bone density as a function of the cellular activity can be due to the overloading of the structure.
Article
Aim. The aim of this work was to study the effectiveness of the piracetam electrophoresis application in the complex sanatoriumresorttreatment of girls with amenorrhea. Material and methods. 56 girls aged 12 to 17 years were under observation, who were treated in the gynecological department ofthe children’s clinical sanatorium “Zdravnitsa”. Primary amenorrhea was recorded in 15 girls, secondary amenorrhea in 41. Long-termresults of sanatorium-resort treatment were studied in 8 girls with secondary amenorrhea. The control group consisted of 20 healthygirls, comparable in age, who underwent hormonal studies. Results. Upon admission to the sanatorium, the main complaint of all girls was the absence of menstruation, many had chronicinflammatory pathology of the ENT organs and pathology of the musculoskeletal system. There was a decrease in ovarian steroidogenesis,while hypoestrogenism was observed in the majority of patients. Girls with amenorrhea are characterized by a high levelof vertigo, an average level of anxiety, fatigue and a fairly low level of irritability. After the sanatorium-resort treatment, an improvementin the general condition of the girls was noted; during their stay in the sanatorium, menstruation was observed in 4 girls withsecondary amenorrhea. After the treatment, a significant positive dynamics of steroid and peptide hormones was revealed in girlswith primary and secondary amenorrhea. In girls with secondary amenorrhea, the ratio of LH/FSH approached the physiological one,but remained significantly higher than normal indicators. Under the influence of sanatorium-resort treatment, the level of adrenalinein the urine normalized in all girls with primary amenorrhea, and in the majority with secondary amenorrhea. There was a positivedynamics of the girls’ psycho-emotional state. According to the long-term results data of sanatorium-resort treatment, the restorationof menstrual function was observed within a year in half of the girls with secondary amenorrhea. Conclusion. The use of the 5% piracetam solution electrophoresis in a complex sanatorium-resort treatment of girls with amenorrheaimproved the general health of girls, normalized hormonal levels and restored menstrual function in half of the girls with secondaryamenorrhea within a year after a course of treatment in the sanatorium.
Article
IntroductionSince the definition of secondary amenorrhea is cessation of regular menses for more than 3 months, it is likely that athletes with irregular menstrual cycles, including oligomenorrhea, do not consider the condition as serious. However, the consequences of untreated oligomenorrhea have not been investigated in elite track and field athletes.Materials and methodsThe cohort consisted of 91 elite-level track and field athletes. Body compositions, including bone parameters and bone turnover markers (BTMs), were measured.ResultsAmong the 91 participants, 52 were eumenorrheic and 33 were oligomenorrheic. The eumenorrheic athletes had significantly higher bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine, lower extremities, and whole body than had the oligomenorrheic athletes (p < 0.01). There were no significant differences in BTMs between the two groups, but oligomenorrheic athletes had significantly lower percent body fat.Conclusion More than 40% of the elite-level female track and field athletes in this study reported menstrual disorders with oligomenorrhea as the most common. However, none sought medical attention. As compared to the eumenorrheic athletes, the oligomenorrheic athletes had lower BMC and BMD. Hence, if an athlete is oligomenorrheic, bone parameter measurements are considerably important.
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Irisin and FGF21 are novel hormones implicated in the "browning" of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14-21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.
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Increasing caloric intake is a promising treatment for exercise-associated amenorrhea, but strategies have not been fully explored. The purpose of this case report was to compare and contrast the responses of two exercising women with amenorrhea of varying duration to an intervention of increased energy intake. Two exercising women with amenorrhea of short (3 months) and long (11 months) duration were chosen to demonstrate the impact of increased caloric intake on recovery of menstrual function and bone health. Repeated measures of dietary intake, eating behavior, body weight, body composition, bone mineral density, resting energy expenditure, exercise volume, serum metabolic hormones and markers of bone turnover, and daily urinary metabolites were obtained. Participant 1 was 19 years old and had a body mass index (BMI) of 20.4 kg/m2 at baseline. She increased caloric intake by 276 kcal/day (1,155 kJ/day, 13%), on average, during the intervention, and her body mass increased by 4.2 kg (8%). Participant 2 was 24 years old and had a BMI of 19.7 kg/m2. She increased caloric intake by 1,881 kcal/day (7,870 kJ/day, 27%) and increased body mass by 2.8 kg (5%). Resting energy expenditure, triiodothyronine, and leptin increased; whereas, ghrelin decreased in both women. Resumption of menses occurred 23 and 74 days into the intervention for the women with short-term and long-term amenorrhea, respectively. The onset of ovulation and regular cycles corresponded with changes in body weight. Recovery of menses coincided closely with increases in caloric intake, weight gain, and improvements in the metabolic environment; however, the nature of restoration of menstrual function differed between the women with short-term versus long-term amenorrhea.
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Importance Diet and exercise represent the mainstays of obesity treatment. No systematic review has been conducted comparing the effect of dietary and exercise intervention in reducing metabolic risks in overweight children.Objective To compare the effects of diet-only intervention with those of diet plus exercise or exercise only on weight loss and metabolic risk reduction in overweight children.Evidence Review English-language articles from 1975 to 2010 available from 7 databases were reviewed. One person searched the databases. Two independent reviewers assessed abstracts and articles against the following eligibility criteria: randomized controlled trials conducted in overweight and obese children aged 18 years or younger, comparing dietary intervention with a diet plus exercise program or an exercise-only program. Study quality was critically appraised by 2 reviewers using established criteria. The main outcome measures were body mass index, body fat percentage, lean body mass, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, and fasting insulin.Findings Fifteen studies were identified and included. Based on the small number of short-term trials currently available, both diet-only and diet plus exercise interventions resulted in weight loss and metabolic profile improvement. However, the addition of exercise to dietary intervention led to greater improvements in levels of high-density lipoprotein cholesterol (3.86 mg/dL [to convert to millimoles per liter, multiply by 0.0259]; 95% CI, 2.70 to 4.63), fasting glucose (−2.16 mg/dL [to convert to millimoles per liter, multiply by 0.0555]; 95% CI, −3.78 to −0.72), and fasting insulin (−2.75 μIU/mL [to convert to picomoles per liter, multiply by 6.945]; 95% CI, −4.50 to −1.00) over 6 months. The diet-only intervention caused greater reductions in levels of triglycerides (at the end of active intervention) and low-density lipoprotein cholesterol (at subsequent follow-up).Conclusions and Relevance This review provides insights into the impact of dietary and exercise interventions on metabolic risk reduction in the pediatric population. However, further studies are required to confirm the evidence with rigorous design, appropriate sample size, longer duration of follow-up, and better strategies to improve compliance and achieve long-term sustainability.
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Objective: To investigate whether high plasma testosterone (T) levels affect areal bone mineral density (aBMD), bone geometry, and bone remodeling in young elite female swimmers (SW). Design: Cross-sectional and 1-year follow-up study. Setting: Pediatric endocrinology and gynecology units. Participant(s): Twenty-five SW and 21 control subjects (CON) with breast stages IV or V (mean age 15.3 ± 1.3 y). Intervention(s): None. Main outcome measure(s): Clinical and biologic parameters, aBMD, and bone geometry. Result(s): Two groups of SW were constituted on the basis of total T level. High T level SW (HSW; n = 15) presented higher T than SW with normal T (NSW; n = 10) and CON (0.63 ± 0.17; 0.36 ± 0.07, and 0.38 ± 0.14 ng/mL, respectively). The SHBG level (62.1 ± 18.7 vs. 43.3 ± 19.8 nmol/L) and the LH/FSH ratio (1.7 ± 1.1 vs. 0.9 ± 0.5) were higher, and menstrual disorders (60% vs. 23.8%) were more frequent in HSW than CON, and no difference was observed between the three groups for other sex hormones and insulin-like growth factor (IGF) 1 or IGF-binding protein 3. SW presented lower fat mass in the whole body and higher lean mass in the upper limbs only. aBMD was only modestly increased in the upper limbs in the SW groups, but no other bone-specific differences (aBMD, bone geometry, bone turnover markers) were demonstrated between SW and CON at baseline or for aBMD after 1 year in a subgroup of participants. Conclusion(s): High plasma T levels have no detectable effect on bone mass and bone geometry in SW during the period of peak bone mass acquisition.
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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.
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We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass.
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Intense physical activity in peripubertal girls may delay menarche and cause menstrual disorders and estrogen deficiency, particularly in sport disciplines that require strict weight control. It may also have a deleterious effect on bone mass acquisition. The aim of this study was to determine the time-course of bone mass accretion in peripubertal elite female rhythmic gymnasts (FRGs) over a 1-year period, as well as the anthropometric and hormone parameters that could be helpful for predicting bone mineral density (BMD) gain. We conducted a 1-year follow-up study in 29 FRGs (10.7-16.1 years old). Whole body composition and BMD of the whole body, proximal femur, lumbar spine, mid-radius, and skull were measured by dual energy X-ray absorptiometry (DXA). Moreover, baseline growth- and bone metabolism-related hormones such as IGF1, IGF-binding protein 3 (IGFBP3), leptin, and bone markers were measured. BMD increased significantly at all bone sites throughout puberty, particularly between Tanner stages II and IV-V (P=0.025 to P<0.001). The IGF1 level, IGF1/IGFBP3 ratio, and leptin level were higher in late pubertal stages (i.e. IV-V) compared with early stage (i.e. I). In simple and multivariate analyses, only the IGF1/IGFBP3 ratio was strongly correlated with the BMD change at all bone sites (r=0.49, P=0.02 to r=0.77, P<0.0001). This 1-year follow-up study of peripubertal FRGs showed that BMD gain was maximal around Tanner stage III. The plasma IGF1/IGFBP3 ratio was associated with bone mass acquisition in this period, and it may thus serve as a surrogate marker of bone mass gain in this population.
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The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. At age 17, subjects with the highest E2 levels in year 1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.
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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.
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The purpose of this study was to determine the effect of a 15-week diet and exercise intervention program on energy balance, hormonal profiles, body composition, and menstrual function of an amenorrheic endurance athlete. The intervention program reduced training 1 day/week and included the use of a sport nutrition beverage providing 360 kcal/day. Three eumenorrheic athletes served as a comparison group and were monitored over the same 15-week period. The amenorrheic athlete experienced a transition from negative to positive energy balance, increased body fat from 8.2 to 14.4%, increased fasting luteinizing hormone (LH) from 3.9 to 7.3 mIU/ml, and decreased fasting cortisol from 41.2 to 33.2 micrograms/dl. The eumenorrheic subjects showed a 0.4% reduction in body fat, a decrease in follicular phase levels of LH from 7.9 to 6.5 mIU/ml, and no change in cortisol. These results suggest that nonpharmacological treatment can contribute to reestablishing normal hormonal profiles and menstrual cyclicity in amenorrheic athletes.
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The possibility that chronic nutritional deficiency alters leptin regulation and its link to reproductive function was investigated by determining serum leptin levels during a 24-h period with controlled nutrient intake in highly trained athletes with and without menstrual cyclicity and in BMI-matched cycling sedentary controls (n = 8 per group). Our data show that 24th leptin levels were reduced equally (3-fold, P < 0.001) in both cyclic and amenorrheic athletes as compared to controls. Low leptin levels in the athletic groups were consistent with their reduction in body fat (r = 0.91, P < 0.0001) relative to BMI, but were also influenced by the presence of low insulin (r = 0.70, P < 0.001) and elevated cortisol (r = -0.65, P < 0.001) levels. A diurnal pattern of 24h leptin levels, with an approximate 50% rise (P < 0.001) from nadir (0900h) to peak (0100h), was present in normally cycling athletes and controls and was strikingly absent in amenorrheic athletes. The absolute increase in leptin levels from nadir to peak was directly related to insulin excursions in response to meals (r = 0.60, P = .002) and inversely related to the amplitude of the 24h cortisol rhythm (r = -0.70, P = .0002). These findings are consistent with a link between the functionality of adipocytes, nutritional status, and integrity of the reproductive axis in humans.
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Physical activity is known to have an anabolic effect on bone tissue. It has been shown to increase the bone mineral density (BMD) in young adults, as well as in teenagers. But there is little information about the effect of intensive physical activity in childhood, particularly at the prepubertal stage. To examine the influence of an early intensive physical training on BMD, we have studied a group of elite prepubertal girls, at the starting phase of their peak bone mass acquisition. Subjects were engaged either in sport requiring significant impact loading on the skeleton, or in sport without impact loading. Forty-one healthy prepubertal girls took part in this study. The sport group consisted of 10 swimmers (10.5 ± 1.4 years old) and 18 gymnasts (10.4 ± 1.3 years old), who had performed 3 years of high-level sport training (8-12 h per week for swimmers, 10-15 h per week for gymnasts). Thirteen girls (10.7 ± 1 years old) doing less than 3 h per week of physical activity served as a control group. BMD measurements were done using dual-energy X-ray absorptiometry. There was no statistical significant difference between groups as regards age, body height and weight, and body composition. There was no statistical significant difference between swimmers and controls for all the BMD measurements. Mean BMD in gymnasts was statistically higher than in the control group for mid-radius (± 15.5%, p < 0.001), distal radius (± 33%, p < 0.001), L2-4 vertebrae (± 11%, p < 0.05), femoral neck (+ 15%, p < 0.001) and Ward's triangle (+ 15%, p < 0.01). Moreover, at radius, trochanter and femoral normative values. We conclude that physical activity in childhood could be an important factor in bone mineral acquisition in prepubertal girls, but only if the sport can induce bone strains during a long-term program: gymnastics has such characteristics, unlike swimming. Such acquisition could provide protection against risks of osteoporosis in later life, but this remains debatable.
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Physical activity has a beneficial effect on bone development in circumpubertal children, although its effect on younger children is uncertain. In this cross-sectional study, we examined associations between physical activity and bone measures in 368 preschool children (mean age: 5.2 years, range: 4-6 years). Physical activity was measured using 4-day accelerometry readings, parental report of children's usual physical activity, and parental report of children's hours of daily television viewing. Total body and site-specific bone mineral content and area bone mineral density (BMD) were measured by dual energy radiograph absorptiometry. After adjustment for age and body size, accelerometry measures of physical activity and parental report of usual physical activity were consistently and positively associated with bone mineral content and BMD in both boys and girls (r = 0.15-0.28). Television viewing was inversely associated with hip BMD in girls (r = -0.15). The proportion of variance in bone measures explained by physical activity in linear regression models ranged from r(2) = 1.5% to 9.0%. In all of these models except total body BMD, at least 1 and often several of the physical activity variables entered as independent predictors. Activity variables most likely to enter the regression models were vigorous physical activity (as determined by accelerometry) and parental ranking of child's usual physical activity. Findings indicate that there are statistically significant and, perhaps important, associations between physical activity and bone measures during early childhood, well ahead of the onset of peak bone mass. This would suggest that intervention strategies to increase physical activity in young children could contribute to optimal bone development.
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The purpose of this study was to determine if physical activity, aerobic fitness and isometric strength during adolescence were predictors of cardiovascular risk factor levels in young adulthood. The following measurements were carried out: maximal oxygen uptake (VO(2)max), maximal voluntary contraction (MVC) in four muscle groups, physical activity (questionnaire), blood pressure (BP), total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, anthropometric variables and body fat % (sum of four skinfolds). The data were collected from the Danish Youth and Sports study, an observational longitudinal study in which two measurements were carried out over an eight-year period. The findings in this study indicated that the relationships between the absolute levels of physical fitness and activity in adolescence and the subsequent level of CVD risk factors are weak. However, the changes in physical fitness and physical activity were related to the absolute levels of CVD risk factors in young adulthood, especially in men. Weak relationships were found between the changes in physical fitness/activity and changes in CVD risk factor levels in both sexes. In conclusion, many subjects changed their levels of physical activity and physical fitness between adolescence and young adulthood and the changes, especially in aerobic fitness, seemed to be the best predictor of CVD risk factor levels in young adulthood.
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Hypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.
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Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.
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The purpose of this 7-year prospective longitudinal study was to examine whether the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L(2)-L(4)) were assessed by dual-energy X-ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (G(LL)), consistently high (G(HH)), and changed from low to high (G(LH)) and from high to low (G(HL)) during 7 years of follow-up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the G(LL) group, the G(HH) group had higher BMC (11.7% in the TF, p < .05) and BMD at the TB (4.5%) and the TF (12.2%, all p < .05) at age 18. Those in the G(LH) group also had higher a BMC at each site (8.5% to 9.4%, p < .05) and a higher BMD in the TB (5.4%) and the TF (8.9%) than that of G(LL) (all p < 0.05) at the age 18. Our results suggest that long-term leisure-time physical activity has a positive effect on bone mass gain of multiple bone sites in girls during the transition from prepuberty to early adulthood. In addition, girls whose physical activity increases during adolescence also benefit from bone mass gain.
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Although hypoleptinaemia has been reported in female peripubertal athletes, data are lacking on leptin and bone mass variations in puberty and the effects of leptin on bone mineralization during this period. This study therefore investigated the variations in leptin level and bone mineral density (BMD) in young elite female rhythmic gymnasts (FRG) according to pubertal stage. The effects of leptin, IGF-1 and sex hormones on bone mineral acquisition were also evaluated. Plasma leptin levels were analysed in 43 elite FRG (mean age: 13.3 +/- 1.8 years range: 10.6-17.2, body mass index: 17.52 +/- 1.85 kg/m(2), training status: 17.9-23.8 h/week) according to their pubertal stage (Tanner I, n = 7; II, n = 10; III, n = 9; IV, n = 8; V, n = 9). IGF-1, IGFBP-3 and sex hormones were also evaluated. BMD was measured by dual-energy X-ray absorptiometry at various bone sites. Plasma leptin increased throughout pubertal growth and the values measured in Tanner stages IV-V were significantly higher than in stages I-II. Gains in BMD were measured throughout puberty at all bone sites, particularly between Tanner stages II and IV. In simple correlation analysis, BMD at all bone sites was positively correlated with plasma leptin, age, bone age, BMI, oestrogen, testosterone, IGF-1 and IGFBP-3. However, multivariate analysis using a linear regression model by block (including bone age, anthropometric data and biological parameters) was then performed to determine the factors independently associated with each BMD site, and only bone age, fat-free soft tissue and BMI remained independent predictors. In FRG characterized by high training volume and low fat mass, plasma leptin levels increased throughout puberty and were partially related to body composition changes. Despite the simultaneous increases in plasma leptin and BMD during pubertal growth, it was not possible to differentiate the leptin impact on bone independently from anthropometric parameters.
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Childhood obesity is increasingly prevalent in the community and is related to adverse cardiovascular outcomes during adulthood. In this study of healthy children, we evaluated the influence of adiposity and physical activity on carotid-femoral pulse wave velocity (PWV), an index of arterial stiffness and a marker of cardiovascular risk in adults. In 573 community-based children (mean age: 10.1+/-0.3 years; 51% boys), we measured body mass index and waist circumference. Percentage body fat was quantitated by dual-energy x-ray absorptiometry. Cardiorespiratory fitness (CRF) and physical activity levels were assessed using a 20-m shuttle run and 7-day pedometer count, respectively. PWV was estimated by applanation tonometry. In univariate analysis, PWV was positively correlated with body mass index (r=0.34), waist circumference (r=0.32), and percentage body fat (r=0.32; P<0.001 for all) and negatively correlated with CRF (r=-0.23; P<0.001) and pedometer count (r=-0.08; P=0.046). In separate multivariable linear regression models, body mass index, waist circumference, and percentage of body fat were independently and positively associated with PWV (P<0.01 for all) after adjusting for age, sex, systolic blood pressure, mean arterial pressure, heart rate, and CRF (P<0.01 for all). The influence of CRF on PWV was attenuated after adjusting for adiposity. In conclusion, increased body mass and adiposity and decreased CRF are associated with arterial stiffening in healthy prepubescent children.
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Late menarche is a risk factor for fragility fractures. We hypothesized that pubertal timing-dependent alterations in bone structural components would persist from peak bone mass to menopause, independent of premenopausal bone loss. We studied the influence of menarcheal age (MENA) on femoral neck BMD (FN aBMD) by DXA and microstructure of distal tibia by HR-pQCT in healthy young adult (YAD; 20.4 +/- 0.6 [SD] yr, n = 124) and premenopausal middle-aged (PREMENO; 45.8 +/- 3.4 yr, n = 120) women. Median of MENA was 13.0 +/- 1.2 and 13.1 +/- 1.7 yr in YAD and PREMENO, respectively. In YAD and PREMENO (n = 244), FN aBMD (R = -0.29, p = 0.013), as well as total volumetric BMD (Dtot; R = -0.23, p = 0.006) and cortical thickness (Ct.Th; R = -0.18, p = 0.011) of distal tibia were inversely correlated to MENA. After segregation by the median of MENA in EARLY and LATE subgroups, the significant influences of both MENA (p = 0.004) and chronological age (p < 0.0001) were observed for FN aBMD and trabecular bone volume fraction of the distal tibia with similar differences in T-scores between LATE and EARLY subgroups in YAD (-0.36 and -0.31 T-scores) and PREMENO (-0.35 and -0.42 T-scores) women. Ct.Th was negatively influenced by MENA, whereas trabecular thickness (Tb.Th) was negatively influenced by chronological age. There was a striking inverse relationship between cross-sectional area and Ct.Th (R = -0.57, p < 0.001). In conclusion, the negative influence of late menarcheal age at weight-bearing sites as observed by the end of skeletal growth remains unattenuated a few years before menopause and is independent of premenopausal bone loss. Alterations in both bone mineral mass and microstructural components may explain the increased risk of fragility fractures associated with later menarcheal age.
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The benefits of exercise are widely recognized, however physically active women can develop exercise associated menstrual cycle disturbances such as amenorrhea (i.e., estrogen deficiency) secondary to a chronic energy deficiency. To assess the effects of exercise status and estrogen deficiency on osteoprotegerin (OPG) and its relationship to bone resorption in premenopausal exercising women. Cross-sectional study of serum OPG, urinary c-telopeptides (uCTX), urinary estrone 3-glucuronide (E1G), urinary pregnanediol 3-glucuronide (PdG) and bone mineral density (BMD) measured on multiple occasions in 67 women. Volunteers were retrospectively grouped: 1) sedentary menstruating group (SedMen n=8), 2) exercising menstruating group (ExMen, n=36), and 3) exercising amenorrheic group (ExAmen, n=23). One-way ANOVAs were performed, and LSD post-hoc tests were performed when differences were detected. Subjects were similar with respect to age (24.2+/-1.0 years), weight (57.8+/-1.7 kg), and height (164.3+/-1.3 cm) (p>0.05). ExMen and ExAmen groups were more aerobically fit (p=0.003) and had less body fat (p=0.002) than the SedMen group. Resting energy expenditure/fat free mass was lowest (p=0.001) in the ExAmen groups. Mean E1G across the measurement period (p<0.001) and overall E1G exposure as assessed by E1G area under the curve (AUC) (p<0.001) were lower in the ExAmen group vs. the SedMen and ExMen groups. U-CTX-I was elevated (p=0.033) in the ExAmen group (281.8+/-40.3 microg/L/mmCr), compared with the SedMen and ExMen groups (184.5+/-22.4, 197.2+/-14.7 microg/L/mmCr, respectively). OPG was suppressed (p=0.005) in the ExAmen group (4.6+/-0.2 pmol/L) vs. ExMen group (5.2+/-0.2 pmol/L), and OPG was lower in the SedMen group (4.1+/-0.3 pmol/L) compared with the ExMen group. Findings were translated to BMD; the ExAmen group had suppressed total body BMD (p=0.014) and L2-L4 BMD (p=0.015) vs. the ExMen group. Our results suggest that OPG responds to the bone loading effect of exercise, and that suppressed OPG may play a role in the etiology of increased bone resorption observed in exercising women with chronic estrogen deficiency secondary to hypothalamic amenorrhea.
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The relationship of prior menstrual irregularities and current menstrual status to the bone density of 97 young athletes was determined at seven sites using single- and dual-photon absorptiometry. Menstrual patterns were ranked on a scale of 1 to 9 in terms of their potential adverse affect on bone. Only vertebral density was significantly related to menstrual patterns (r = -.43). Women who had always had regular cycles had higher lumbar densities (1.27 g/cm2) than those with a history of oligomenorrhea/amenorrhea interspersed with regular periods (1.18 g/cm2). The lumbar density of both groups exceeded that of women who had never had regular cycles (1.05 g/cm2). Body weight became more important as a predictor variable as the severity of menstrual irregularities increased. The combination of menstrual pattern and body weight predicted 43% of the total variation in lumbar density. These data suggest that extended periods of oligomenorrhea/amenorrhea may have a residual effect on lumbar bone density.
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The high percentage of fat (about 26-28%) in the mature human female may influence reproductive ability directly: 1) as an extragonadal source of estrogen; and 2) by influencing the direction of metabolism of estrogen to the most potent or least potent forms. The slow maturation of the hypothalamus and pituitary up to menarche, or first estrus, is accompanied by a slow maturation of the body, which changes not only in size but in the relative proportion of bone, muscle, and fat. Evidence is presented that a particular ratio of fat to lean mass is normally necessary for puberty and the maintenance of female reproductive ability in the human and rat. The synchronizing signals may be metabolic, relating food intake to core temperature and fat depots.
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To examine the role of skeletal loading patterns on bone mineral density (BMD), we compared eumenorrheic athletes who chronically trained by opposite forms of skeletal loading, intensive weight-bearing activity (gymnastics, n = 13), and nonweightbearing activity (swimming, n = 26) and 19 nonathletic controls. BMD (g/cm2) of the lumbar spine, femoral neck, trochanter, and whole body was assessed by dual energy X-ray absorptiometry (DXA). Subregion analysis of the whole body scan permitted BMD evaluation of diverse regions. Swimmers were taller (p = 0.0001), heavier (p < 0.005), and had a greater bone-free lean mass (p < 0.001) than gymnasts and nonathletic controls. When adjusted for body surface area, there was no difference in lean mass between swimmers and gymnasts, and both were higher than controls (p < 0.01). Gymnasts had a lower (p < 0.005) fat mass than swimmers and controls. There were no group differences for spine or whole body BMD, but gymnasts had higher spine BMD corrected for body mass than either swimmers or controls. Gymnasts (1.117 +/- 0.110) had higher femoral neck BMD than controls (0.974 +/- 0.105), who were higher than swimmers (0.875 +/- 0.105) (p = 0.0001). This result still applied when BMD was normalized for body weight and bone size. Trochanter BMD of gymnasts (0.898 +/- 0.130) was also higher than controls (0.784 +/- 0.097) and swimmers (0.748 +/- 0.085) (p = 0.0002), and remained higher when corrected for body mass.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Female athletes exhibit a higher prevalence of exercise-associated amenorrhea and oligomenorrhea compared with nonathletic women, and both conditions are related to reduced bone mineral density (BMD), particularly at the spine. This study investigated bone mass and oligomenorrhea and amenorrhea in two groups of competitive female athletes with different skeletal loading patterns: gymnasts and runners. Bone mineral density (g/cm2) of the femoral neck, lumbar spine (L2-4), and whole body was assessed by dual energy X-ray absorptiometry (QDR-1000/W, Hologic Inc., Waltham, MA) in collegiate gymnasts (n = 21) and runners (n = 20), and nonathletic college women (n = 19). The runners and gymnasts had similar values for percent body fat (14.7 +/- 2.2% and 15.6 +/- 2.9%, respectively), which were lower (p < 0.001) than controls (22.3 +/- 3.0%). Lean body mass (LBM) did not differ among the groups, but when adjusted for body surface area, gymnasts had a higher LBM/height2 (p = 0.0001) compared with runners and controls. Muscle strength was significantly greater (p < 0.05) in gymnasts for quadriceps, biceps, and hip adductor force, compared with runners and controls. Gymnasts had a significantly later menarche age (16.2 +/- 1.7 years) compared with runners (14.4 +/- 1.7 years) and controls (13.0 +/- 1.2 years). The prevalence of oligo- and amenorrhea was 47% for gymnasts (6 amenorrheic, 4 oligomenorrheic), 30% for runners (3 amenorrheic, 3 oligomenorrheic), and 0% for controls. Furthermore, athletic groups had similar menstrual histories given the higher proportion of gymnasts who had experienced primary amenorrhea. When evaluated since menarche, however, runners had somewhat longer histories due to an earlier age at menarche and slightly older ages. Dietary calcium intake did not differ among groups, although mean values were below the RDA of 1200 mg/day. By athletic group, BMD at any site did not differ among women with amenorrhea versus oligomenorrhea versus eumenorrhea, although there was a trend for the regularly menstruating athletes in both groups to have slightly higher values. Lumbar spine BMD was lower (p = 0.0001) in runners (0.98 +/- 0.11 g/cm2) compared with both gymnasts and controls (1.17 +/- 0.13 and 1.11 +/- 0.11 g/cm2, respectively). Femoral neck BMD differed among all groups (p = 0.0001): gymnasts = 1.09 +/- 0.12 g/cm2 > controls = 0.97 +/- 0.10 g/cm2 > runners = 0.88 +/- 0.11 g/cm2. Whole body BMD was lower (p < 0.01) in runners (1.04 +/- 0.06 g/cm2) compared with gymnasts and controls (1.11 +/- 0.08 and 1.09 +/- 0.06 g/cm2, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
Article
The purposes of this study were to determine bone mineral density (BMD) of female college gymnasts (N = 26) and age- (+/- 1.0 yr), height- (+/- 5.1 cm), and weight- (+/- 2.3 kg) matched controls (N = 26) using dual energy x-ray absorptiometry and to examine the relationship of physical activity, diet, menstrual history, and BMD in these athletes. Energy expenditure, dietary intake and menstruation were assessed using standardized questionnaires. The BMD of the gymnasts were significantly (all P < 0.0001) higher than controls for the lumbar spine (L1-4), total proximal femur, femoral neck, Ward's triangle, and whole body. Mean calcium and kcal intakes for both groups were lower than the Recommended Dietary Allowances, and gymnasts had significantly lower kcal intakes than controls (P < 0.05). More gymnasts than controls (59% vs 24%) reported that their menstrual cycle had been interrupted at some point since menarche (P < 0.02). The major finding of this investigation is that the BMD of gymnasts were higher than matched controls despite the fact that gymnasts as a group had inadequate dietary calcium and a higher propensity to have an interruption of their menstrual cycle.
Article
The fat-derived hormone, leptin, is proposed to serve as an adipostatic signal to the brain to reduce food intake and body weight. In addition to its effects on body weight, chronic leptin treatment restores puberty and fertility to ob/ob mice with total leptin deficiency, and acute treatment substantially corrects hypogonadism in mice starved for 2 d without affecting body weight. Leptin may therefore be a critical signal, linking adiposity and reproduction. Since body weight and adiposity appear to play a critical role in the timing of puberty in humans and rodents, and leptin levels rise with increasing adiposity, we studied the effects of once daily injections of recombinant leptin on the onset of puberty in female mice weaned on day 21 and fed ad libitum. There was a linear increase in body weight during the study period, which was not altered by the dose of leptin used. Mice injected with leptin had an earlier onset of three classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared with saline-injected controls. Leptin is the first peripheral molecule demonstrated to accelerate the maturation of the reproductive axis in normal rodents. We propose that leptin is the signal that informs the brain that energy stores are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.
Article
Leptin is the protein product of the recently cloned ob gene, that has been implicated in the control of body weight and thermogenesis, but also independently stimulates the reproductive axis. As major changes in body composition and gonadal function occur during human adolescence, we have assessed serum leptin concentration through childhood. Serum leptin was measured in a radioimmunoassay in samples from 235 healthy children from 5 to 18 years of age. Its relationship to body mass index (BMI) (expressed as standard deviation score (SDS)) and the changes in concentration both within and between sexes over the stages of puberty were analysed. Serum leptin was present at similar concentrations in both sexes over the prepubertal years and increased in parallel into early puberty (breast stage (B) 2, genital stage (G) 2). Thereafter serum leptin in the boys declined to a nadir in G5. In contrast in girls, leptin remained constant in mid-puberty rising to a peak at B5. Factors influencing leptin (BMI SDS, age and testicular volume) were assessed therefore in the pre- and peripubertal stages (B1-2, G1-2) compared to the later pubertal stages (B3-5, G3-5). In all groups, leptin was positively correlated to BMI SDS (r2 = 38-41% in girls, r2 = 31-35% in boys). However in B1-2 and G1-2, leptin was also positively related to age, which contributed a further 27% and 20% respectively to the variability. In B3-5, age only accounted for an additional 5% in leptin variability. In contrast in G3-5, leptin was related positively to BMI SDS (r2 = 35%) and negatively to testicular volume (r2 = 24%). The influence of BMI on leptin is a significant factor throughout the prepubertal and pubertal years of both sexes. The additional negative effect of testicular volume in the boys contributes to the sexual dichotomy in leptin concentration at the completion of puberty. The similar rise in leptin over the prepubertal years into early puberty in both sexes, related not only to BMI SDS but also independently to age, would suggest that leptin may have a facilitatory role in human pubertal development.
Article
The largest voluntary loads on bones come from muscles. To adapt bone strength and mass to them, special strain threshold ranges determine where modeling adds and strengthens bone, and where remodeling conserves or removes it, just as different thermostat settings control the heating and cooling systems in a house. If estrogen lowers the remodeling threshold, two things should occur. First, at puberty in girls, bone mass should begin to increase more than in boys with similar muscle strengths, owing to reduced remodeling-dependent bone losses, while gains from longitudinal bone growth and bone modeling continue normally. That increase in bone mass in girls should plateau when their muscle strength stops increasing, since their stronger bones could then reduce bone strains enough to turn modeling off, but could let remodeling keep conserving existing bone. Second, decreased estrogen secretion [or a related factor(s)], as during menopause, should raise the remodeling threshold and make remodeling begin removing that extra bone. That removal should also tend to plateau after the remaining and weaker bone lets bone strains rise to the higher threshold. Postmenopausal bone loss shows the second effects. Previously unremarked relationships in the data of a 1995 Argentine study showed the first effects. This supports the idea that estrogen can affect human bone strength and mass by lowering the remodeling threshold, and loss of estrogen would raise the threshold and help cause postmenopausal bone loss even if other factors help to do it. The Argentine study also suggested ways to study those things and the roles of muscle strength and other factors in controlling bone strength and mass in children and adult humans. Those factors included, in part, hormones, vitamins, calcium, diet, sex, race, age, medications, cytokines, genetic errors, gene expression patterns, and disease.
Article
We tested two hypotheses about the disruption of luteinizing hormone (LH) pulsatility in exercising women by assaying LH in blood samples drawn at 10-min intervals over 24 h from nine young, habitually sedentary, regularly menstruating women on days 8, 9, or 10 of two menstrual cycles after 4 days of intense exercise [E = 30 kcal.kg lean body mass (LBM)-1.day-1 at 70% of aerobic capacity]. To test the hypothesis that LH pulsatility is disrupted by low energy availability, we controlled the subjects' dietary energy intakes (I) to set their energy availabilities (A = I - E) at 45 and 10 kcal.kg LBM-1.day-1 during the two trials. To test the hypothesis that LH pulsatility is disrupted by the stress of exercise, we compared the resulting LH pulsatilities to those previously reported in women with similar controlled energy availability who had not exercised. In the exercising women, low energy availability reduced LH pulse frequency by 10% (P < 0.01) during the waking hours and increased LH pulse amplitude by 36% (P = 0.05) during waking and sleeping hours, but this reduction in LH pulse frequency was blunted by 60% (P = 0.03) compared with that in the previously studied nonexercising women whose low energy availability was caused by dietary restriction. The stress of exercise neither reduced LH pulse frequency nor increased LH pulse amplitude (all P > 0.4). During exercise, the proportion of energy derived from carbohydrate oxidation was reduced from 73% while A = 45 kcal.kg LBM-1.day-1 to 49% while A = 10 kcal.kg LBM-1.day-1 (P < 0.0001). These results contradict the hypothesis that LH pulsatility is disrupted by exercise stress and suggest that LH pulsatility in women depends on energy availability.
Article
In this model of estrogen effects on bone, a postulated mediator mechanism in marrow would affect modeling and remodeling only of bone next to or close to it. That mediator mechanism could sense estrogen. In response to that hormone, it would let remodeling of bone next to marrow proceed in its conservation mode. This would minimize losses of that bone and tend to prevent an osteopenia. But acute estrogen deficiency would make that mechanism switch remodeling of bone next to marrow to its disuse mode. Meanwhile, conservation-mode remodeling would continue for haversian and subperiosteal bone. The resulting losses of bone next to marrow would expand marrow cavities, thin cortices, and reduce trabecular bone "mass," but would not reduce outside bone diameters. That scheme could explain the osteopenia that follows natural or experimental estrogen deficiency in mammalian females. If so, as estrogen secretion rises in girls at puberty they should begin accumulating more bone next to marrow. They do. Also if so, at menopause women should begin to lose that bone. They do. Those effects would exist in addition to known effects of estrogen on existing osteoclasts and osteoblasts.
Article
Women have become increasingly physically active in recent decades. While exercise provides substantial health benefits, intensive exercise is also associated with a unique set of risks for the female athlete. Hypothalamic dysfunction associated with strenuous exercise, and the resulting disturbance of GnRH pulsatility, can result in delayed menarche and disruption of menstrual cyclicity. Specific mechanisms triggering reproductive dysfunction may vary across athletic disciplines. An energy drain incurred by women whose energy expenditure exceeds dietary energy intake appears to be the primary factor effecting GnRH suppression in athletes engaged in sports emphasizing leanness; nutritional restriction may be an important causal factor in the hypoestrogenism observed in these athletes. A distinct hormonal profile characterized by hyperandrogenism rather than hypoestrogenism is associated with athletes engaged in sports emphasizing strength over leanness. Complications associated with suppression of GnRH include infertility and compromised bone density. Failure to attain peak bone mass and bone loss predispose hypoestrogenic athletes to osteopenia and osteoporosis. Metabolic aberrations associated with nutritional insult may be the primary factors effecting low bone density in hypoestrogenic athletes, thus diagnosis should include careful screening for abnormal eating behavior. Increasing caloric intake to offset high energy demand may be sufficient to reverse menstrual dysfunction and stimulate bone accretion. Treatment with exogenous estrogen may help to curb further bone loss in the hypoestrogenic amenorrheic athlete, but may not be sufficient to stimulate bone growth. Treatment aimed at correcting metabolic abnormalities may in fact prove more effective than that aimed at correcting estrogen deficiencies.
Article
To evaluate the effects of an elementary school-based physical education exercise intervention program on bone mineral accrual in prepubertal and early pubertal girls. A total of 14 schools were randomly assigned to control (C) and intervention (I) groups. Girls in the I group completed a 10-minute, 3 times per week circuit of varied jumping activities over 7 months. We measured total body, lumbar spine, proximal femur, femoral neck, and trochanteric bone mineral content and areal bone mineral density and estimated femoral neck volumetric bone mineral density at baseline and final measurement in 87 girls in the I group and 90 girls in the C group. Girls were between 8.7 and 11.7 years at baseline. Tanner stage 1 girls were considered prepubertal; Tanner stages 2 and 3 girls were considered early pubertal. We used analysis of covariance (adjusting for baseline bone values, change in size, age, and maturity) to compare 7-month change in bone mineral content, areal bone mineral density, and volumetric bone mineral density between C and I groups within prepubertal and early pubertal girls. There was no difference in 7-month change in bone parameters between prepubertal I and C groups. Early pubertal girls in the I group gained 1.5% to 3.1% more bone at the femoral neck and lumbar spine than early pubertal girls in the C group (P <.05); gain at other sites did not differ. In girls, early puberty may be a particularly opportune time during growth for simple exercise interventions to have a positive effect on bone health.
Article
LOUCKS, A. B. Energy availability, not body fatness, regulates reproductive function in women. Exerc. Sport Sci. Rev., Vol. 31, No. 3, pp. 144–148, 2003. The morbid consequences of menstrual disorders in athletes require medical diagnosis and treatment. Reproductive disruption appears to occur when energy availability (dietary energy intake minus exercise energy expenditure) falls below a threshold between 20 and 30 kcal ·kgLBM−1·d−1, and some women may be more severely affected than others by subthreshold energy availability.
Article
To investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium. Clinical, placebo-controlled, randomized trial study.Healthy volunteers in an academic research environment. Fifty-five dancers (mean age: 22.0 +/- 4.6, age at menarche: 14.7 +/- 2.3 years), including 24 amenorrheics. Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day. Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine. Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization. These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea.
Article
Childhood weight-bearing physical activity is recognized as an important determinant of peak bone mass, and physical activity intervention may represent a feasible strategy for primary prevention of osteoporosis. Previous school-based exercise interventions have all been of <10 months in duration. We implemented a high-impact, circuit-based, jumping intervention (10 minutes, 3 times a week) over 2 school years and compared changes in bone mineral content (BMC) over 20 months (2 school years) in 9.9 +/- 0.6-year-old intervention girls (N = 32) and controls (10.3 +/- 0.4 years, N = 43). We measured BMC for the total body, lumbar spine, proximal femur (and femoral neck and trochanteric subregions), and lean and fat mass by dual-energy radiograph absorptiometry (Hologic QDR 4500), and height, sitting height, leg length, and weight at baseline and 20 months. We assessed Tanner stage, general physical activity, and calcium intake by questionnaire. Girls were Tanner breast stage 1 to 3 at baseline. There were no significant differences in baseline or 20-month change in body size or composition, average physical activity, or calcium intake between groups. There were substantially greater gains in lumbar spine (41.7% vs 38.0%) and femoral neck (24.8% vs 20.2%) BMC in intervention than in control girls (P <.05, analysis of covariance; covariates were baseline BMC and height, change in height, physical activity, and final Tanner stage). Three brief sessions of high-impact exercise per week implemented over 2 consecutive years within the elementary school curriculum elicited a substantial bone mineral accrual advantage in pubertal girls.
Article
Physical activity causes acute physiological and long-term adaptive responses in the body. It is a protective factor for coronary heart disease (CHD) in adults. It has been assumed that children younger than 8 years of age may be in general active enough and there would be hardly any relationships between physical activity and CHD risk factors in early childhood. One hundred and fifty-five children (age 4-7 years) participated in this physical activity study during three consecutive years. Physical activity was examined twice a year with a special-purpose physical activity diary. CHD risk factors were measured during annual health care visits in the Specific Turku Coronary Risk-Factor Intervention Project (STRIP). We found that physical activity was related to CHD risk factors in early childhood. Among the girls, low-activity playing was related to a higher BMI. At the mean age of 6 years, high-activity playing was negatively related to serum total cholesterol (r=-0.32*) and positively to the high-density lipoprotein (HDL)/total cholesterol ratio (r=0.37**). The negative relationship between high-activity playing and triglycerides was highest (r=-0.32*) at the mean age of six. Among 4-year-old boys, playing outdoors correlated positively with serum HDL cholesterol concentration (r=0.29*) and the HDL/total ratio (r=0.35**). At the age of 5 years, physically active playing correlated positively with systolic blood pressure (r=0.25*). Playing outdoors and high-activity playing already have important health-maintaining effects in 4-7-year-old children. These positive effects differ between genders. (*P<0.05 **P<0.01)
Article
The KiSS-1 gene codes for a family of neuropeptides called kisspeptins which bind to the G-protein-coupled receptor GPR54. To assess the possible effects of kisspeptins on gonadotropin secretion, we injected kisspeptin-52 into the lateral cerebral ventricles of adult male rats and found that kisspeptin-52 increased the serum levels of luteinizing hormone (p < 0.05). To determine whether the kisspeptin-52-induced stimulation of luteinizing hormone secretion was mediated by gonadotropin-releasing hormone (GnRH), we pretreated adult male rats with a GnRH antagonist (acyline), then challenged the animals with intracerebroventricularly administered kisspeptin-52. The GnRH antagonist blocked the kisspeptin-52-induced increase in luteinizing hormone. To examine whether kisspeptins stimulate transcriptional activity in GnRH neurons, we administered kisspeptin-52 intracerebroventricularly and found by immunocytochemistry that 86% of the GnRH neurons coexpressed Fos 2 h after the kisspeptin-52 challenge, whereas fewer than 1% of the GnRH neurons expressed Fos following injection of the vehicle alone (p < 0.001). To assess whether kisspeptins can directly act on GnRH neurons, we used double-label in situ hybridization and found that 77% of the GnRH neurons coexpress GPR54 mRNA. Finally, to determine whether KiSS-1 gene expression is regulated by gonadal hormones, we measured KiSS-1 mRNA levels by single-label in situ hybridization in intact and castrated males and found significantly higher levels in the arcuate nucleus of castrates. These results demonstrate that GnRH neurons are direct targets for regulation by kisspeptins and that KiSS-1 mRNA is regulated by gonadal hormones, suggesting that KiSS-1 neurons play an important role in the feedback regulation of gonadotropin secretion.
Article
Alterations in resting energy expenditure and metabolic hormones (energy conservation) are evident in increasing magnitude across a continuum of increasing severity of clinical menstrual disturbances, including luteal-phase defects, anovulation, and amenorrhea in exercising women. These data provide further evidence of the tight association between energy balance and reproduction and suggest that subtle declines in energy availability can produce clinically recognized menstrual disturbances.