Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa
TL;DR: It is concluded that physiologic estradiol replacement increases spine and hip BMD in girls with AN, even after controlling for baseline age and weight.
Abstract: Background
Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low bone mineral density (BMD) in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiological estrogen doses that mimic puberty on BMD has not been examined.
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TL;DR: The IOC RED-S consensus authors have reconvened to provide an update summary of the interim scientific progress in the field of relative energy deficiency with the ultimate goal of stimulating advances inRED-S awareness, clinical application and scientific research to address current gaps in knowledge.
Abstract: In 2014, the IOC published a consensus statement entitled ‘Beyond the Female Athlete Triad: Relative Energy Deficiency in Sport (RED-S)’. The syndrome of RED-S refers to ‘impaired physiological functioning caused by relative energy deficiency and includes, but is not limited to, impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis and cardiovascular health’. The aetiological factor of this syndrome is low energy availability (LEA).1
The publication of the RED-S consensus statement stimulated activity in the field of Female Athlete Triad science, including some initial controversy2 3 followed by numerous scientific publications addressing:
1. The health parameters identified in the RED-S conceptual model (figure 1).1 4
2. Relative energy deficiency in male athletes.
3. The measurement of LEA.
4. The performance parameters identified in the RED-S conceptual model (figure 2).1 4
The IOC RED-S consensus authors have reconvened to provide an update summary of the interim scientific progress in the field of relative energy deficiency with the ultimate goal of stimulating advances in RED-S awareness, clinical application and scientific research to address current gaps in knowledge.
Figure 1
Health consequences of Relative Energy Deficiency in Sport (RED-S) showing an expanded concept of the Female Athlete Triad to acknowledge a wider range of outcomes and the application to male athletes (*Psychological consequences can either precede RED-S or be the result of RED-S).1 4
Figure 2
Potential Performance consequences of Relative Energy Deficiency in Sport (*Aerobic and anerobic performance).1 4
### Low energy availability
LEA, which underpins the concept of RED-S, is a mismatch between an athlete’s energy intake (diet) and the energy expended in exercise, leaving inadequate energy to support the functions required by the body to maintain optimal health and performance. Operationally, energy availability (EA) is defined as:
![Formula][1]
where exercise energy expenditure (EEE) is calculated as the additional energy expended above that of …
[1]: /embed/mml-math-1.gif
476 citations
447 citations
TL;DR: Specific evidence based psychological and pharmacological treatments are recommended for most eating disorders but more trials are needed for specific therapies in anorexia nervosa, and research is urgently needed for all aspects of ARFID assessment and management.
Abstract: Objectives:This clinical practice guideline for treatment of DSM-5 feeding and eating disorders was conducted as part of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clini...
418 citations
Cites background from "Physiologic estrogen replacement in..."
...Recently, use of physiological levels of oestrogen (via a hormonal patch) and progesterone in an RCT was associated with improvement in bone density, and may have a place in therapy (Misra and Klibanski, 2011; Misra et al., 2011)....
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TL;DR: This consensus statement represents a set of recommendations developed following the 1st and 2nd International Symposia on the Female Athlete Triad and is intended to provide clinical guidelines for physicians, athletic trainers and other healthcare providers for the screening, diagnosis and treatment of the Female athlete Triad.
Abstract: The Female Athlete Triad is a medical condition often observed in physically active girls and women, and involves three components: (1) low energy availability with or without disordered eating, (2) menstrual dysfunction and (3) low bone mineral density. Female athletes often present with one or more of the three Triad components, and an early intervention is essential to prevent its progression to serious endpoints that include clinical eating disorders, amenorrhoea and osteoporosis. This consensus statement represents a set of recommendations developed following the 1st (San Francisco, California, USA) and 2nd (Indianapolis, Indiana, USA) International Symposia on the Female Athlete Triad. It is intended to provide clinical guidelines for physicians, athletic trainers and other healthcare providers for the screening, diagnosis and treatment of the Female Athlete Triad and to provide clear recommendations for return to play. The 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad expert panel has proposed a risk stratification point system that takes into account magnitude of risk to assist the physician in decision-making regarding sport participation, clearance and return to play. Guidelines are offered for clearance categories, management by a multidisciplinary team and implementation of treatment contracts. This consensus paper has been endorsed by the Female Athlete Triad Coalition, an International Consortium of leading Triad researchers, physicians and other healthcare professionals, the American College of Sports Medicine and the American Medical Society for Sports Medicine.
407 citations
TL;DR: The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.
Abstract: Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.
384 citations
References
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11 Jun 2013
113,134 citations
Book•
01 Jun 1999
TL;DR: This Atlas is principally based on the Brush Foundation Study of Human Growth and Development, conceived in 1929 by Professor T. Wingate Todd and obtained in the six years subsequent to Todd's publication of his Atlas of Skeletal Maturation of the Hand.
Abstract: This Atlas is principally based on the Brush Foundation Study of Human Growth and Development, conceived in 1929 by Professor T. Wingate Todd of Western Reserve University School of Medicine. This intensive study collected data on the maturation of human anatomy through the meticulous X-raying of a series of research subjects enrolled in the study as juveniles-some as young as three months-and thereafter routinely weighed and measured at three-month to one-year intervals, depending on their age. This Atlas utilizes not only the X-ray films to which Todd had access but, also, those which were obtained in the six years subsequent to Todd's publication of his Atlas of Skeletal Maturation of the Hand. The X-ray standards in the present volume are, therefore, the first to be based exclusively on the research of the Brush Foundation Study.
4,750 citations
TL;DR: Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects.
Abstract: Background Disruptions in hypothalamic–gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. Methods Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving recombinant human leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (±SD) of 8.5±8.1 months. Results Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects. In contrast, recombinant leptin treatment increased mean LH lev...
763 citations
TL;DR: Bone mineral apparent density (BMAD) is presented, which is BMC normalized to a derived bone reference volume, which minimizes the effect of bone geometry and allows comparisons of mineral status among bones of similar shape but different size.
Abstract: We studied the acquisition of bone mineral in 45 healthy prepubertal and pubertal girls and related changes in bone mass to age, body mass, pubertal status, calcium intake, and exercise. A subgroup of 12 girls was followed longitudinally. Bone mineral content (BMC) of the lumbar spine, whole body, and femoral neck was measured by dual energy x-ray absorptiometry and that at the midradius by single photon absorptiometry. For comparison, spine and whole body mineral contents were also measured by dual photon absorptiometry. Bone mass was expressed in conventional terms of BMC and area density (BMD). However, we show that BMD fails to account for differences in bone thickness. Since bone size increases during adolescence, we present a new expression, bone mineral apparent density (BMAD), which is BMC normalized to a derived bone reference volume. This term minimizes the effect of bone geometry and allows comparisons of mineral status among bones of similar shape but different size. BMC increased with age at all sites. These increases were most rapid in the early teens and plateaued after 16 yr of age. When bone mineral values at all sites were regressed against age, height, weight, or pubertal stage, consistent relationships emerged, in which BMC was most strongly correlated, BMD was correlated to an intermediate degree, and BMAD correlated only modestly or without significance. Dietary calcium and exercise level did not correlate significantly with bone mass. From these relationships, we attribute 50% of the pubertal increase in spine mineral and 99% of the change in whole body mineral to bone expansion rather than to an increase in bone mineral per unit volume. In multiple regressions, pubertal stage most consistently predicted mineral status. This study emphasizes the importance of pubertal development and body size as determinants of bone acquisition in girls. BMAD may prove to be particularly useful in studies of bone acquisition during periods of rapid skeletal growth.
729 citations
"Physiologic estrogen replacement in..." refers methods in this paper
...We calculated lumbar spine bone mineral apparent density (LBMAD, a height-adjusted measure of spine BMD) using published methods.((24)) Because of lack of standards, Z-scores for LBMAD are not reported....
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TL;DR: Anorexia nervosa is more common among girls 15-19 years old it is a very common chronic illness and its incidence has increased among females 15-24 years old but not among older women or among males.
Abstract: Objective The aim of the study was to determine incidence and prevalence rates and long-term trends in incidence of anorexia nervosa by identifying all persons residing in the community of Rochester, Minn., during the 50-year period 1935 through 1984 who had the disorder. Method From a community-based epidemiologic resource, 13,559 medical records with diagnoses of amenorrhea, starvation, weight loss, anorexia nervosa, or other conditions were screened to identify true cases of anorexia nervosa determined by using standard diagnostic criteria. Results One hundred eighty-one residents (166 female and 15 male) fulfilled the diagnostic criteria for anorexia nervosa; these were the incidence cases. Due to a quadratic trend in the rates for girls 10-19 years old, the incidence rate among female residents fell from 16.6 per 100,000 person-years in the 1935-1939 period to a low of 7.0 in 1950-1954 and increased to 26.3 in 1980-1984. The incidence rates for women 20 years old and older and for males remained constant. For females 15-24 years old, there was a linear increase. The overall age-adjusted incidence rate per 100,000 person-years was 14.6 for females and 1.8 for males. The prevalence rate per 100,000 population was 269.9 for females and 22.5 for males. Conclusions Anorexia nervosa is more common than previously recognized. Among girls 15-19 years old it is a very common chronic illness. Its incidence has increased among females 15-24 years old but not among older women or among males.
578 citations
"Physiologic estrogen replacement in..." refers background or methods in this paper
...We also examined differences in AN Eþ girls versus AN E– girls after controlling for (1) baseline age, height, and weight changes, for (2) baseline age, years since menarche, and weight changes, for (3) baseline age, duration of amenorrhea, and weight Table 2....
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...Anorexia nervosa (AN), a condition characterized by low weight and hypogonadism,((1)) is prevalent in adolescence((2)) and is associated with decreased BMD and bone accrual....
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