CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(05): 395-402
DOI: 10.1055/s-0041-1730289
Review Article

The Female Athlete Triad/Relative Energy Deficiency in Sports (RED-S)

A tríade da atleta feminina/déficit energético relativo no esporte (RED-S)
1   Maternidade Dr. Alfredo da Costa, Centro Hospitalar Universitário, Lisboa, Portugal
,
1   Maternidade Dr. Alfredo da Costa, Centro Hospitalar Universitário, Lisboa, Portugal
,
1   Maternidade Dr. Alfredo da Costa, Centro Hospitalar Universitário, Lisboa, Portugal
,
2   Hospital Garcia de Orta, Lisboa, Portugal
,
1   Maternidade Dr. Alfredo da Costa, Centro Hospitalar Universitário, Lisboa, Portugal
› Institutsangaben

Abstract

In a healthy athlete, the caloric intake is sufficient for sports energy needs and body physiological functions, allowing a balance between energy availability, bone metabolism, and menstrual cycle. On the other hand, an imbalance caused by low energy availability due to a restrictive diet, eating disorders or long periods of energy expenditure leads to multisystemic deregulation favoring the essential functions of the body. This phenomenon, described as the female athlete triad, occurs in a considerable percentage of high-performance athletes, with harmful consequences for their future. The present review was carried out based on a critical analysis of the most recent publications available and aims to provide a global perception of the topic relative energy deficit in sport (RED-S). The objective is to promote the acquisition of more consolidated knowledge on an undervalued theme, enabling the acquisition of preventive strategies, early diagnosis and/or appropriate treatment.

Resumo

Em uma atleta saudável, o aporte calórico é suficiente para a necessidade energética esportiva e para as funções fisiológicas corporais, permitindo um equilíbrio entre disponibilidade energética (DE), metabolismo ósseo e função menstrual. Por outro lado, um desequilíbrio devido à baixa disponibilidade energética (BDE) por dieta restritiva, perturbações alimentares ou grandes períodos de gasto energético conduz a uma desregulação multissistêmica priorizando as funções essenciais do corpo. Este fenômeno, descrito inicialmente como tríade da mulher atleta e, atualmente, como défice energético relativo no esporte (RED-S, na sigla em inglês) tem como pilares a BDE, disfunção menstrual e alterações na densidade mineral óssea (DMO), estando presente em uma percentagem considerável de atletas de alta competição, com consequências nefastas para o seu futuro a curto, médio e longo prazo. A presente revisão foi realizada a partir da análise crítica das publicações mais recentes disponíveis e pretende proporcionar uma percepção global do tema RED-S. O objetivo é promover a aquisição de um conhecimento mais consolidado sobre uma temática subvalorizada, possibilitando a aquisição de estratégias preventivas, diagnóstico precoce e/ou tratamento adequado.

Contributors

All authors were involved in the design and interpretation of the analyses, contributed to the writing of the manuscript, and read and approved the final manuscript.




Publikationsverlauf

Eingereicht: 15. Juni 2020

Angenommen: 18. Februar 2021

Artikel online veröffentlicht:
02. Juni 2021

© 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Yeager KK, Agostini R, Nattiv A, Drinkwater B. The female athlete triad: disordered eating, amenorrhea, osteoporosis. Med Sci Sports Exerc 1993; 25 (07) 775-777 DOI: 10.1249/00005768-199307000-00003.
  • 2 Nattiv A, Loucks AB, Manore MM, Sanborn CF, Sundgot-Borgen J, Warren MP. American College of Sports Medicine. American College of Sports Medicine position stand. The female athlete triad. Med Sci Sports Exerc 2007; 39 (10) 1867-1882 DOI: 10.1249/mss.0b013e318149f111.
  • 3 De Souza MJ, Nattiv A, Joy E, Misra M, Williams NI, Mallinson RJ. et al; 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; 48 (04) 289 DOI: 10.1136/bjsports-2013-093218.
  • 4 Mountjoy M, Sundgot-Borgen JK, Burke LM, Ackerman KE, Blauet C, Constantini N. et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J Sports Med 2018; 52 (11) 687-697 DOI: 10.1136/bjsports-2018-099193.
  • 5 Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C. et al. The IOC consensus statement: beyond the Female Athlete Triad--Relative Energy Deficiency in Sport (RED-S). Br J Sports Med 2014; 48 (07) 491-497 DOI: 10.1136/bjsports-2014-093502.
  • 6 Lages AS, Rebelo-Marques AR, Carrilho F. Défice Energético Relativo no Desporto (RED-S). Rev Med Desportiva Inf 2018; 9 (05) 14-16 DOI: 10.23911/Defice_Energetico_Relativo_no_Desporto.
  • 7 Loucks AB, Thuma JR. Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women. J Clin Endocrinol Metab 2003; 88 (01) 297-311 DOI: 10.1210/jc.2002-020369.
  • 8 Pauli SA, Berga SL. Athletic amenorrhea: energy deficit or psychogenic challenge?. Ann N Y Acad Sci 2010; 1205: 33-38 DOI: 10.1111/j.1749-6632.2010.05663.x.
  • 9 Dufour DL, Sauther ML. Comparative and evolutionary dimensions of the energetics of human pregnancy and lactation. Am J Hum Biol 2002; 14 (05) 584-602 DOI: 10.1002/ajhb.10071.
  • 10 Loucks AB. Low energy availability in the marathon and other endurance sports. Sports Med 2007; 37 (4-5): 348-352 DOI: 10.2165/00007256-200737040-00019.
  • 11 Rodriguez-Pacheco F, Martinez-Fuentes AJ, Tovar S, Pinilla L, Tena-Sempere M, Dieguez C. et al. Regulation of pituitary cell function by adiponectin. Endocrinology 2007; 148 (01) 401-410 DOI: 10.1210/en.2006-1019.
  • 12 Mitchell M, Armstrong DT, Robker RL, Norman RJ. Adipokines: implications for female fertility and obesity. Reproduction 2005; 130 (05) 583-597 DOI: 10.1530/rep.1.00521.
  • 13 Ackerman KE, Slusarz K, Guereca G, Pierce L, Slattery M, Mendes N. et al. Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls. Am J Physiol Endocrinol Metab 2012; 302 (07) E800-E806 DOI: 10.1152/ajpendo.00598.2011.
  • 14 Franks PW, Farooqi IS, Luan J, Wong M-Y, Halsall I, O'Rahilly S. et al. Does physical activity energy expenditure explain the between-individual variation in plasma leptin concentrations after adjusting for differences in body composition?. J Clin Endocrinol Metab 2003; 88 (07) 3258-3263 DOI: 10.1210/jc.2002-021426.
  • 15 Donato Jr J, Cravo RM, Frazão R, Gautron L, Scott MM, Lachey J. et al. Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. J Clin Invest 2011; 121 (01) 355-368 DOI: 10.1172/JCI45106.
  • 16 Misra M, Miller KK, Kuo K, Griffin K, Stewart V, Hunter E. et al. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metab 2005; 289 (02) E347-E356 DOI: 10.1152/ajpendo.00615.2004.
  • 17 Christo K, Cord J, Mendes N, Miller KK, Goldstein MA, Klibanski A. et al. Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study. Clin Endocrinol (Oxf) 2008; 69 (04) 628-633 DOI: 10.1111/j.1365-2265.2008.03237.x.
  • 18 Scheid JL, De Souza MJ. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines. Med Sport Sci 2010; 55: 82-102 DOI: 10.1159/000321974.
  • 19 Lawson EA, Ackerman KE, Estella NM, Estella NM, Guereca G, Pierce L. et al. Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parameters. Eur J Endocrinol 2013; 168 (03) 457-464 DOI: 10.1530/EJE-12-0869.
  • 20 Lawson EA. The effects of oxytocin on eating behaviour and metabolism in humans. Nat Rev Endocrinol 2017; 13 (12) 700-709 DOI: 10.1038/nrendo.2017.115.
  • 21 Afinogenova Y, Schmelkin C, Plessow F, Thomas JJ, Pulumo R, Micali N. et al. Low fasting oxytocin levels are associated with psychopathology in anorexia nervosa in partial recovery. J Clin Psychiatry 2016; 77 (11) e1483-e1490 DOI: 10.4088/JCP.15m10217.
  • 22 Rickenlund A, Thorén M, Carlström K, von Schoultz B, Hirschberg AL. Diurnal profiles of testosterone and pituitary hormones suggest different mechanisms for menstrual disturbances in endurance athletes. J Clin Endocrinol Metab 2004; 89 (02) 702-707 DOI: 10.1210/jc.2003-030306.
  • 23 Misra M, Klibanski A. Endocrine consequences of anorexia nervosa. Lancet Diabetes Endocrinol 2014; 2 (07) 581-592 DOI: 10.1016/S2213-8587(13)70180-3.
  • 24 Laughlin GA, Yen SS. Nutritional and endocrine-metabolic aberrations in amenorrheic athletes. J Clin Endocrinol Metab 1996; 81 (12) 4301-4309 DOI: 10.1210/jcem.81.12.8954031.
  • 25 Gordon CM, Goodman E, Emans SJ, Grace E, Becker KA, Rosen CJ. et al. Physiologic regulators of bone turnover in young women with anorexia nervosa. J Pediatr 2002; 141 (01) 64-70 DOI: 10.1067/mpd.2002.125003.
  • 26 Trombetti A, Richert L, Herrmann FR, Chevalley T, Graf JD, Rizzoli R. Selective determinants of low bone mineral mass in adult women with anorexia nervosa. Int J Endocrinol 2013; 2013: 897193 DOI: 10.1155/2013/897193.
  • 27 Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J. et al. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab 2003; 88 (12) 5615-5623 DOI: 10.1210/jc.2003-030532.
  • 28 Estour B, Germain N, Diconne E, Frere D, Cottet-Emard J-M, Carrot G. et al. Hormonal profile heterogeneity and short-term physical risk in restrictive anorexia nervosa. J Clin Endocrinol Metab 2010; 95 (05) 2203-2210 DOI: 10.1210/jc.2009-2608.
  • 29 Gordon CM. Clinical practice. Functional hypothalamic amenorrhea. N Engl J Med 2010; 363 (04) 365-371 DOI: 10.1056/NEJMcp0912024.
  • 30 Berga SL, Mortola JF, Girton L, Suh B, Laughlin G, Pham P. et al. Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1989; 68 (02) 301-308 DOI: 10.1210/jcem-68-2-301.
  • 31 Michopoulos V, Mancini F, Loucks TL, Berga SL. Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial. Fertil Steril 2013; 99 (07) 2084-91.e1 DOI: 10.1016/j.fertnstert.2013.02.036.
  • 32 Schorr M, Lawson EA, Dichtel LE, Klibanski A, Miller KK. Cortisol measures across the weight spectrum. J Clin Endocrinol Metab 2015; 100 (09) 3313-3321 DOI: 10.1210/JC.2015-2078.
  • 33 Ackerman KE, Patel KT, Guereca G, Pierce L, Herzog DB, Misra M. Cortisol secretory parameters in young exercisers in relation to LH secretion and bone parameters. Clin Endocrinol (Oxf) 2013; 78 (01) 114-119 DOI: 10.1111/j.1365-2265.2012.04458.x.
  • 34 Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M. et al. Functional hypothalamic amenorrhea: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2017; 102 (05) 1413-1439 DOI: 10.1210/jc.2017-00131.
  • 35 Martin B, Golden E, Carlson OD, Egan JM, Mattson MP, Maudsley S. Caloric restriction: impact upon pituitary function and reproduction. Ageing Res Rev 2008; 7 (03) 209-224 DOI: 10.1016/j.arr.2008.01.002.
  • 36 Elliott-Sale KJ, Tenforde AS, Parziale AL, Holtzman B, Ackerman KE. Endocrine effects of relative energy deficiency in sport. Int J Sport Nutr Exerc Metab 2018; 28 (04) 335-349 DOI: 10.1123/ijsnem.2018-0127.
  • 37 Weiss Kelly AK, Hecht S. COUNCIL ON SPORTS MEDICINE AND FITNESS. The female athlete triad. Pediatrics 2016; 138 (02) e20160922 DOI: 10.1542/peds.2016-0922.
  • 38 Nichols JF, Rauh MJ, Barrack MT, Barkai HS, Pernick Y. Disordered eating and menstrual irregularity in high school athletes in lean-build and nonlean-build sports. Int J Sport Nutr Exerc Metab 2007; 17 (04) 364-377 DOI: 10.1123/ijsnem.17.4.364.
  • 39 Beals KA, Hill AK. The prevalence of disordered eating, menstrual dysfunction, and low bone mineral density among US collegiate athletes. Int J Sport Nutr Exerc Metab 2006; 16 (01) 1-23 DOI: 10.1123/ijsnem.16.1.1.
  • 40 Hotta M, Fukuda I, Sato K, Hizuka N, Shibasaki T, Takano K. The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa. J Clin Endocrinol Metab 2000; 85 (01) 200-206 DOI: 10.1210/jcem.85.1.6321.
  • 41 Dominguez J, Goodman L, Sen Gupta S, Mayer L, Etu SF, Walsh BT. et al. Treatment of anorexia nervosa is associated with increases in bone mineral density, and recovery is a biphasic process involving both nutrition and return of menses. Am J Clin Nutr 2007; 86 (01) 92-99 DOI: 10.1093/ajcn/86.1.92.
  • 42 Viapiana O, Gatti D, Dalle Grave R, Todesco T, Rossini M, Braga V. et al. Marked increases in bone mineral density and biochemical markers of bone turnover in patients with anorexia nervosa gaining weight. Bone 2007; 40 (04) 1073-1077 DOI: 10.1016/j.bone.2006.11.015.
  • 43 Ihle R, Loucks AB. Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res 2004; 19 (08) 1231-1240 DOI: 10.1359/JBMR.040410.
  • 44 Ackerman KE, Nazem T, Chapko D, Russell M, Mendes N, Taylor AP. et al. Bone microarchitecture is impaired in adolescent amenorrheic athletes compared with eumenorrheic athletes and nonathletic controls. J Clin Endocrinol Metab 2011; 96 (10) 3123-3133 DOI: 10.1210/jc.2011-1614.
  • 45 Mitchell DM, Tuck P, Ackerman KE, Sokoloff NC, Woolley R, Slattery M. et al. Altered trabecular bone morphology in adolescent and young adult athletes with menstrual dysfunction. Bone 2015; 81: 24-30 DOI: 10.1016/j.bone.2015.06.021.
  • 46 Ackerman KE, Putman M, Guereca G, Taylor AP, Pierce L, Herzog D. et al. Cortical microstructure and estimated bone strength in young amenorrheic athletes, eumenorrheic athletes and non-athletes. Bone 2012; 51 (04) 680-687 DOI: 10.1016/j.bone.2012.07.019.
  • 47 Ackerman KE, Cano Sokoloff N, DE Nardo Maffazioli G, Clarke HM, Lee H, Misra M. Fractures in relation to menstrual status and bone parameters in young athletes. Med Sci Sports Exerc 2015; 47 (08) 1577-1586 DOI: 10.1249/MSS.0000000000000574.
  • 48 Young N, Formica C, Szmukler G, Seeman E. Bone density at weight-bearing and nonweight-bearing sites in ballet dancers: the effects of exercise, hypogonadism, and body weight. J Clin Endocrinol Metab 1994; 78 (02) 449-454 DOI: 10.1210/jcem.78.2.8106634.
  • 49 Robinson TL, Snow-Harter C, Taaffe DR, Gillis D, Shaw J, Marcus R. Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea. J Bone Miner Res 1995; 10 (01) 26-35 DOI: 10.1002/jbmr.5650100107.
  • 50 Friday KE, Drinkwater BL, Bruemmer B, Chesnut III C, Chait A. Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake. J Clin Endocrinol Metab 1993; 77 (06) 1605-1609 DOI: 10.1210/jcem.77.6.8263148.
  • 51 O'Donnell E, De Souza MJ. The cardiovascular effects of chronic hypoestrogenism in amenorrhoeic athletes: a critical review. Sports Med 2004; 34 (09) 601-627 DOI: 10.2165/00007256-200434090-00004.
  • 52 O'Donnell E, Harvey PJ, Goodman JM, De Souza MJ. Long-term estrogen deficiency lowers regional blood flow, resting systolic blood pressure, and heart rate in exercising premenopausal women. Am J Physiol Endocrinol Metab 2007; 292 (05) E1401-E1409 DOI: 10.1152/ajpendo.00547.2006.
  • 53 Hoch AZ, Papanek P, Szabo A, Widlansky ME, Schimke JE, Gutterman DD. Association between the female athlete triad and endothelial dysfunction in dancers. Clin J Sport Med 2011; 21 (02) 119-125 DOI: 10.1097/JSM.0b013e3182042a9a.
  • 54 Puder JJ, Monaco SE, Sen Gupta S, Wang J, Ferin M, Warren MP. Estrogen and exercise may be related to body fat distribution and leptin in young women. Fertil Steril 2006; 86 (03) 694-699 DOI: 10.1016/j.fertnstert.2006.02.085.
  • 55 Fogelholm M. Effects of bodyweight reduction on sports performance. Sports Med 1994; 18 (04) 249-267 DOI: 10.2165/00007256-199418040-00004.
  • 56 Areta JL, Burke LM, Camera DM, West DW, Crawshaw S, Moore DR. et al. Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit. Am J Physiol Endocrinol Metab 2014; 306 (08) E989-E997 DOI: 10.1152/ajpendo.00590.2013.
  • 57 Vanheest JL, Rodgers CD, Mahoney CE, De Souza MJ. Ovarian suppression impairs sport performance in junior elite female swimmers. Med Sci Sports Exerc 2014; 46 (01) 156-166 DOI: 10.1249/MSS.0b013e3182a32b72.
  • 58 Melin A, Tornberg AB, Skouby S, Faber J, Ritz C, Sjödin A. et al. The LEAF questionnaire: a screening tool for the identification of female athletes at risk for the female athlete triad. Br J Sports Med 2014; 48 (07) 540-545 DOI: 10.1136/bjsports-2013-093240.
  • 59 Perkins RB, Hall JE, Martin KA. Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation. J Clin Endocrinol Metab 1999; 84 (06) 1905-1911 DOI: 10.1210/jcem.84.6.5823.
  • 60 Thangavelu K, Geetanjali S. Menstrual disturbance and galactorrhea in people taking conventional antipsychotic medications. Exp Clin Psychopharmacol 2006; 14 (04) 459-460 DOI: 10.1037/1064-1297.14.4.459.
  • 61 Illingworth P. Amenorrhea, anovulation, and dysfunctional uterine bleeding. In: Jameson JL, De Groot LJ. eds. Endocrinology: adult and pediatric. Philadelphia: Saunders/Elsevier; 2010: 2341-55
  • 62 Rebar R. Evaluation of amenorrhea, anovulation, and abnormal bleeding. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K. et al., eds. Endotext. South Dartmouth: MDText.com, Inc.; 2000
  • 63 Bulun SE. Physiology and pathology of the female reproductive axis. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. eds. Williams textbook of endocrinology. 13th ed.. Philadelphia: Elsevier; 2016: 590-664
  • 64 Golden NH, Carlson JL. The pathophysiology of amenorrhea in the adolescent. Ann N Y Acad Sci 2008; 1135: 163-178 DOI: 10.1196/annals.1429.014.
  • 65 Frumar AM, Meldrum DR, Judd HL. Hypercarotenemia in hypothalamic amenorrhea. Fertil Steril 1979; 32 (03) 261-264
  • 66 Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 2016; 106 (01) 6-15 DOI: 10.1016/j.fertnstert.2016.05.003.
  • 67 Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007; 92 (02) 405-413 DOI: 10.1210/jc.2006-1864.
  • 68 Pinola P, Piltonen TT, Puurunen J, Vanky E, Sundström-Poromaa I, Stener-Victorin E. et al. Androgen profile through life in women with polycystic ovary syndrome: a Nordic multicenter collaboration study. J Clin Endocrinol Metab 2015; 100 (09) 3400-3407 DOI: 10.1210/jc.2015-2123.
  • 69 Warren MP, Holderness CC, Lesobre V, Tzen R, Vossoughian F, Brooks-Gunn J. Hypothalamic amenorrhea and hidden nutritional insults. J Soc Gynecol Investig 1994; 1 (01) 84-88 DOI: 10.1177/107155769400100117.
  • 70 La Marca A, Pati M, Orvieto R, Stabile G, Carducci Artenisio A, Volpe A. Serum anti-müllerian hormone levels in women with secondary amenorrhea. Fertil Steril 2006; 85 (05) 1547-1549 DOI: 10.1016/j.fertnstert.2005.10.057.
  • 71 Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, Fulheihan GE-H, Kescskemethy HH. et al; International Society for Clinical Densitometry. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom 2014; 17 (02) 225-242 DOI: 10.1016/j.jocd.2014.01.003.
  • 72 Bachrach LK, Guido D, Katzman D, Litt IF, Marcus R. Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics 1990; 86 (03) 440-447
  • 73 Soyka LA, Misra M, Frenchman A, Miller KK, Grinspoon S, Schoenfeld DA. et al. Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 2002; 87 (09) 4177-4185 DOI: 10.1210/jc.2001-011889.
  • 74 Grinspoon S, Thomas E, Pitts S, Gross E, Mickley D, Miller K. et al. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Intern Med 2000; 133 (10) 790-794 DOI: 10.7326/0003-4819-133-10-200011210-00011.
  • 75 Moreira CA, Bilezikian JP. Stress fractures: concepts and therapeutics. J Clin Endocrinol Metab 2017; 102 (02) 525-534 DOI: 10.1210/jc.2016-2720.
  • 76 Kim BY, Kraus E, Fredericson M. et al. Serum vitamin D levels are inversely associated with time lost to bone stress injury in a cohort of NCAA division I distance runners. Clin J Sport Med 2016; 26 (02) e61
  • 77 NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285 (06) 785-795 DOI: 10.1001/jama.285.6.785.
  • 78 De Souza MJ, Williams NI. Beyond hypoestrogenism in amenorrheic athletes: energy deficiency as a contributing factor for bone loss. Curr Sports Med Rep 2005; 4 (01) 38-44 DOI: 10.1007/s11932-005-0029-1.
  • 79 Warren MP, Brooks-Gunn J, Fox RP, Holderness CC, Hyle EP, Hamilton WG. et al. Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study. Fertil Steril 2003; 80 (02) 398-404 DOI: 10.1016/s0015-0282(03)00660-5.
  • 80 Cobb KL, Bachrach LK, Sowers M, Nieves J, Greendale GA, Kent KK. et al. The effect of oral contraceptives on bone mass and stress fractures in female runners. Med Sci Sports Exerc 2007; 39 (09) 1464-1473 DOI: 10.1249/mss.0b013e318074e532.
  • 81 Southmayd EA, De Souza MJ. A summary of the influence of exogenous estrogen administration across the lifespan on the GH/IGF-1 axis and implications for bone health. Growth Horm IGF Res 2017; 32: 2-13 DOI: 10.1016/j.ghir.2016.09.001.
  • 82 Ackerman KE, Singhal V, Baskaran C. et al. Transdermal 17-beta-estradiol has a beneficial effect on bone parameters assessed using HRpQCT compared to oral ethinyl estradiol-progesterone combination pills in oligoamenorrheic athletes: a randomized controlled trial. J Bone Miner Res 2017; 32 (Suppl. 01) S41
  • 83 Fazeli PK, Wang IS, Miller KK, Herzog DB, Misra M, Lee H. et al. Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa. J Clin Endocrinol Metab 2014; 99 (04) 1322-1329 DOI: 10.1210/jc.2013-4105.
  • 84 Zhang D, Potty A, Vyas P, Lane J. The role of recombinant PTH in human fracture healing: a systematic review. J Orthop Trauma 2014; 28 (01) 57-62 DOI: 10.1097/BOT.0b013e31828e13fe.
  • 85 Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM. et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351 (10) 987-997 DOI: 10.1056/NEJMoa040388.
  • 86 Chou SH, Chamberland JP, Liu X, Matarese G, Gao C, Stefanakis R. et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci U S A 2011; 108 (16) 6585-6590 DOI: 10.1073/pnas.1015674108.
  • 87 Santoro N. Update in hyper- and hypogonadotropic amenorrhea. J Clin Endocrinol Metab 2011; 96 (11) 3281-3288 DOI: 10.1210/jc.2011-1419.
  • 88 Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol (1985) 1998; 84 (01) 37-46 DOI: 10.1152/jappl.1998.84.1.37.
  • 89 Cialdella-Kam L, Guebels CP, Maddalozzo GF, Manore MM. Dietary intervention restored menses in female athletes with exercise-associated menstrual dysfunction with limited impact on bone and muscle health. Nutrients 2014; 6 (08) 3018-3039 DOI: 10.3390/nu6083018.