青野敏博：摂食障害と無月経．日本医師会雑誌 1996；116:1073-1076．.
C Mantzoros, J S Flier, M D Lesem, T D Brewerton, D C Jimerson
Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain.
J Clin Endocrinol Metab. 1997 Jun;82(6):1845-51. doi: 10.1210/jcem.82.6.4006.
Abstract/Text
Studies in rodents have shown that leptin acts in the central nervous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects included 11 female patients with anorexia nervosa studied at low weight and after treatment, and 15 healthy female controls. Concentrations of leptin in blood and CSF were measured by RIA. Patients with anorexia nervosa, compared to controls, had decreased concentrations of leptin in CSF (98 +/- 26 vs. 160 +/- 58 pg/mL; P < 0.0005) and plasma (1.75 +/- 0.46 vs. 7.01 +/- 3.92 ng/mL; P < 0.005). The CSF to plasma leptin ratio, however, was higher for patients (0.060 +/- 0.023) than for controls (0.025 +/- 0.007; P < 0.0001). At posttreatment testing, although patients had not yet reached normal body weight, CSF and plasma leptin concentrations had increased to normal levels. These results demonstrate the dynamic changes in plasma and CSF leptin during positive energy balance in anorexia nervosa. The results further suggest that normalization of CSF leptin levels before full weight restoration during treatment of anorexic patients could contribute to resistance to weight gain and/or incomplete weight recovery.
Mary Jane De Souza, Aurelia Nattiv, Elizabeth Joy, Madhusmita Misra, Nancy I Williams, Rebecca J Mallinson, Jenna C Gibbs, Marion Olmsted, Marci Goolsby, Gordon Matheson, Expert Panel
2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad: 1st International Conference held in San Francisco, California, May 2012 and 2nd International Conference held in Indianapolis, Indiana, May 2013.
Br J Sports Med. 2014 Feb;48(4):289. doi: 10.1136/bjsports-2013-093218.
Abstract/Text
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.
Margo Mountjoy, Jorunn Sundgot-Borgen, Louise Burke, Susan Carter, Naama Constantini, Constance Lebrun, Nanna Meyer, Roberta Sherman, Kathrin Steffen, Richard Budgett, Arne Ljungqvist
The IOC consensus statement: beyond the Female Athlete Triad--Relative Energy Deficiency in Sport (RED-S).
Br J Sports Med. 2014 Apr;48(7):491-7. doi: 10.1136/bjsports-2014-093502.
Abstract/Text
Protecting the health of the athlete is a goal of the International Olympic Committee (IOC). The IOC convened an expert panel to update the 2005 IOC Consensus Statement on the Female Athlete Triad. This Consensus Statement replaces the previous and provides guidelines to guide risk assessment, treatment and return-to-play decisions. The IOC expert working group introduces a broader, more comprehensive term for the condition previously known as 'Female Athlete Triad'. The term 'Relative Energy Deficiency in Sport' (RED-S), points to the complexity involved and the fact that male athletes are also affected. The syndrome of RED-S refers to impaired physiological function including, but not limited to, metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular health caused by relative energy deficiency. The cause of this syndrome is energy deficiency relative to the balance between dietary energy intake and energy expenditure required for health and activities of daily living, growth and sporting activities. Psychological consequences can either precede RED-S or be the result of RED-S. The clinical phenomenon is not a 'triad' of the three entities of energy availability, menstrual function and bone health, but rather a syndrome that affects many aspects of physiological function, health and athletic performance. This Consensus Statement also recommends practical clinical models for the management of affected athletes. The 'Sport Risk Assessment and Return to Play Model' categorises the syndrome into three groups and translates these classifications into clinical recommendations.
Margo Mountjoy, Kathryn E Ackerman, David M Bailey, Louise M Burke, Naama Constantini, Anthony C Hackney, Ida Aliisa Heikura, Anna Melin, Anne Marte Pensgaard, Trent Stellingwerff, Jorunn Kaiander Sundgot-Borgen, Monica Klungland Torstveit, Astrid Uhrenholdt Jacobsen, Evert Verhagen, Richard Budgett, Lars Engebretsen, Uğur Erdener
2023 International Olympic Committee's (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs).
Br J Sports Med. 2023 Sep;57(17):1073-1097. doi: 10.1136/bjsports-2023-106994.
Abstract/Text
Relative Energy Deficiency in Sport (REDs) was first introduced in 2014 by the International Olympic Committee's expert writing panel, identifying a syndrome of deleterious health and performance outcomes experienced by female and male athletes exposed to low energy availability (LEA; inadequate energy intake in relation to exercise energy expenditure). Since the 2018 REDs consensus, there have been >170 original research publications advancing the field of REDs science, including emerging data demonstrating the growing role of low carbohydrate availability, further evidence of the interplay between mental health and REDs and more data elucidating the impact of LEA in males. Our knowledge of REDs signs and symptoms has resulted in updated Health and Performance Conceptual Models and the development of a novel Physiological Model. This Physiological Model is designed to demonstrate the complexity of either problematic or adaptable LEA exposure, coupled with individual moderating factors, leading to changes in health and performance outcomes. Guidelines for safe and effective body composition assessment to help prevent REDs are also outlined. A new REDs Clinical Assessment Tool-Version 2 is introduced to facilitate the detection and clinical diagnosis of REDs based on accumulated severity and risk stratification, with associated training and competition recommendations. Prevention and treatment principles of REDs are presented to encourage best practices for sports organisations and clinicians. Finally, methodological best practices for REDs research are outlined to stimulate future high-quality research to address important knowledge gaps.
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岩佐武、松崎利也、苛原稔：ストレス・摂食調節因子によるゴナドトロピン分泌調節．臨床婦人科産科2010；64：1293-1299．.
N H Golden, M S Jacobson, J Schebendach, M V Solanto, S M Hertz, I R Shenker
Resumption of menses in anorexia nervosa.
Arch Pediatr Adolesc Med. 1997 Jan;151(1):16-21.
Abstract/Text
OBJECTIVE: To determine factors associated with resumption of menses (ROM) in adolescents with anorexia nervosa.
DESIGN: Cohort study with 2-year follow-up.
SETTING: Tertiary care referral center.
PATIENTS: Consecutive sample of 100 adolescent girls with anorexia nervosa.
INTERVENTIONS: Body weight, percent body fat, and luteinizing hormone, follicle-stimulating hormone, and estradiol levels were measured at baseline and every 3 months until ROM (defined as 2 or more consecutive spontaneous menstrual cycles). Treatment consisted of a combination of medical, nutritional, and psychiatric intervention aimed at weight gain and resolution of psychological conflicts.
MAIN OUTCOME MEASURES: Body weight, body composition, and hormonal status at ROM.
RESULTS: Menses resumed at a mean (+/-SD) of 9.4 +/- 8.2 months after patients were initially seen and required a weight of 2.05 kg more than the weight at which menses were lost. Mean (+/-SD) percent of standard body weight at ROM was 91.6% +/- 9.1%, and 86% of patients resumed menses within 6 months of achieving this weight. At 1-year follow-up, 47 (68%) of 69 patients had resumed menses and 22 (32%) remained amenorrheic. No significant differences were seen in body weight, body mass index, or percent body fat at follow-up in those who resumed menses by 1 year compared with those who had not. Subjects who remained amenorrheic at 1 year had lower levels of luteinizing hormone (P < .001) and follicle-stimulating hormone (P < .05) at baseline and lower levels of luteinizing hormone (P < .01) and estradiol (P < .001) at follow-up. At follow-up, a serum estradiol level of more than 110 pmol/L (30 pg/mL) was associated with ROM (relative risk, 4.6; 95% confidence interval, 1.9-11.2).
CONCLUSIONS: A weight approximately 90% of standard body weight was the average weight at which ROM occurred and is a reasonable treatment goal weight, because 86% of patients who achieved this goal resumed menses within 6 months. Resumption of menses required restoration of hypothalamic-pituitary-ovarian function, which did not depend on the amount of body fat. Serum estradiol levels at follow-up best assess ROM.
N A Rigotti, R M Neer, S J Skates, D B Herzog, S R Nussbaum
The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of cortical bone mass.
JAMA. 1991 Mar 6;265(9):1133-8.
Abstract/Text
Women with anorexia nervosa have reduced bone mass and may develop fractures. Neither the pathophysiology of this osteoporosis nor its natural history is known. To study the clinical course of osteoporosis, we followed up 27 women with anorexia nervosa for a median of 25 months (range, 9 to 53 months). At study entry, cortical bone density, measured by single-photon absorptiometry of the radial shaft, was low (mean +/- SD, 0.63 +/- 0.07 g/cm2) and inversely related to the duration of amenorrhea (r = -0.49). During follow-up, most patients gained weight (n = 19), took calcium supplements (n = 16), and exercised regularly (n = 22), but fewer than half reached 80% or more of ideal body weight (n = 11), resumed menses (n = 6), or received estrogen (n = 4). Cortical bone density was stable during follow-up for the group as a whole; the mean annual change (+/- SD) was +0.005 (+/- .015) g/cm2 (95% confidence interval, -0.0009 to +0.0109). There was no significant difference in the mean change in bone density between women who attained 80% of ideal weight and those who did not or between groups who did or did not regain menses, take estrogen or calcium, or exercise vigorously. Four fractures were clinically observed in three women during follow-up. The rate of 0.05 nonspine fractures per person-year (95% confidence interval, 0.02 to 0.13) exceeds that of normal women in this age range (relative risk, 7.1; 95% confidence interval, 3.2 to 18.5). We conclude that reductions in cortical bone density appear not to be rapidly reversed by recovery from anorexia nervosa and that anorectic women may have an increased risk of fracture.
