Цель. Разработка дифференциально-диагностических критериев функциональной гипоталамической аменореи (ФГА), возникающей на фоне стресса и энергетического дефицита, на основе сравнительного анализа клинико-лабораторных данных и результатов двухэнергетической рентгеновской абсорбциометрии. Материалы и методы. Проведены клинико-лабораторные обследования 56 пациенток с ФГА, связанной со стрессовыми событиями (1-я группа), и 64 пациенток с ФГА на фоне расстройств пищевого поведения (2-я группа), включающие оценку содержания жировой ткани, определение уровня лептина, индекса жировой ткани и дифференциального индекса. Результаты. Пациентки 2-й группы отличались более выраженным дефицитом содержания жировой ткани и уровня лептина в сравнении с больными 1-й группы. Наиболее информативным показателем в дифференциальной диагностике различных форм ФГА оказался дифференциальный индекс [AUC=0,907 (0,84–0,97)], его пороговое значение составило 21,4, наименее информативным – индекс массы тела [AUC=0,78 (0,71–0,87)]. Заключение. Дифференциальный индекс можно рассматривать как информативный дифференциально-диагностический критерий различных форм ФГА.
Aim. To investigate the usefulness of differential diagnostic criteria of functional hypothalamic amenorrhea (FHA) related to energy deficiency and stress. Materials and methods. There were provided clinical and laboratory examination of 56 patients with FHA associated with stressful events (group 1) and 64 patients with FHA on the background of eating disorders (group 2), including assessment of adipose tissue, determination of leptin level, adipose tissue index and differential index. Results. Patients of group 2 were distinguished by a more significant deficiency of body mass index, total body fat, and leptin levels in comparison with patients of group 1. The differential index [AUC=0.907 (0.84–0.97)] turned out to be the most informative indicator in the differential diagnosis of various forms of FHA, its threshold value was 21.4, the least informative – body mass index [AUC=0.78 (0.71–0.87)]. Conclusion. The differential index can be considered as an informative differential diagnostic criterion for various forms of FHA.
Key words: energy balance, amenorrhea, leptin, body fat, functional hypothalamic amenorrhea.
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3. Ubuka T, Son YL, Tsutsui K. Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone. Gen Comp Endocrinol 2016; 227: 27–50.
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8. Michalaki M, Vagenakis AG, Makri M et al: Dissociation in the early decline in serum T(3) concentration and serum IL-6 and TNFalpha in nonthyroidal illness syndrome induced by abdominal surgery. J Clin Endocrinol Metab 2001; 86: 4198.
9. Чернуха Г.Е., Табеева Г.И., Гусев Д.В., Кузнецов С.Ю. Оценка показателей жировой ткани при функциональной гипоталамической аменорее. Акушерство и гинекология. 2018; 2: 74–80.
[Chernukha G.E., Tabeeva G.I., Gusev D.V., Kuznetsov S.Iu. Otsenka pokazatelei zhirovoi tkani pri funktsional'noi gipotalamicheskoi amenoree. Akusherstvo i ginekologiia. 2018; 2: 74–80 (in Russian).]
10. Liu P, Ma F, Lou H, Liu Y. The utility of fat mass index vs. body mass index and percentage of body fat in the screening of metabolic syndrome. BMC Public Health 2013; 13: 629.
11. Shen ZQ, Xu JJ, Lin JF. Resumption of menstruation and pituitary response to gonadotropin-releasing hormone infunctional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy. J Endocrinol Invest 2015; 36: 812–15.
12. Frisch RE, McArthur JW. Menstrual cycles: Fatness as a determinant of mini- mum weight for height necessary for their maintenance or onset. Science 1974; 185: 949–51.
13. Bachmann KN, Schorr M, Bruno AG et al. Vertebral Volumetric Bone Density and Strength are Impaired in Women with Low-weight and Atypical Anorexia Nervosa. J Clin Endocrinol Metab 2017;102 (1): 57–68. DOI: 10.1210/jc.2016-2099
14. Chan JL, Mantzoros CS. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhea and anorexia nervosa. Lancet 2005; 366:
74.
15. Pinto S, Roseberry AG, Liu H. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 2004; 304 (5667): 110.
16. Peltz G, Aguirre MT, Sanderson M, Fadden MK. The role of fat mass index in determining obesity. Am J Hum Biol 2010; 22 (5), 639–47.
17. Warren IP, Ramos RH, Bronson E. Exercise-associated amenorrhea. Physician Sportsmed 2002; 30: 10.
18. Stokić E, Srdić B, Barak O. Body mass index, body fat mass and the occurrence of amenorrhea in ballet dancers. Gynecol Endocrinol 2005; 20 (4): 195–9.
________________________________________________
1. Berga SL, Loucks TL. Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Ann N Y Acad Sci 2006; 1092: 114.
2. Genazzani AD, Ricchieri F, Lanzoni C et al: Diagnostic and therapeutic approach to hypothalamic amenorrhea. Ann NY Acad Sci 2006; 1092: 103.
3. Ubuka T, Son YL, Tsutsui K. Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone. Gen Comp Endocrinol 2016; 227: 27–50.
4. Fourman LT, Fazeli PK. Neuroendocrine Causes of Amenorrhea – An Update. J Clin Endocrinol Metab 2015; 100 (3): 812–24.
5. Mastorakos G, Pavlatou M, Diamanti-Kandarakis E et al. Exercise and the stress system. Hormones (Athens) 2005; 4: 73.
6. Welt CK, Chan JL, Bullen J et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351: 987–97.
7. Deck CA, Honeycutt JL, Cheung E et al. Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress Response in Vertebrates. Fron Endocrinol 2017; 8.
8. Michalaki M, Vagenakis AG, Makri M et al: Dissociation in the early decline in serum T(3) concentration and serum IL-6 and TNFalpha in nonthyroidal illness syndrome induced by abdominal surgery. J Clin Endocrinol Metab 2001; 86: 4198.
9. Chernukha G.E., Tabeeva G.I., Gusev D.V., Kuznetsov S.Iu. Otsenka pokazatelei zhirovoi tkani pri funktsional'noi gipotalamicheskoi amenoree. Akusherstvo i ginekologiia. 2018; 2: 74–80 (in Russian).
10. Liu P, Ma F, Lou H, Liu Y. The utility of fat mass index vs. body mass index and percentage of body fat in the screening of metabolic syndrome. BMC Public Health 2013; 13: 629.
11. Shen ZQ, Xu JJ, Lin JF. Resumption of menstruation and pituitary response to gonadotropin-releasing hormone infunctional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy. J Endocrinol Invest 2015; 36: 812–15.
12. Frisch RE, McArthur JW. Menstrual cycles: Fatness as a determinant of mini- mum weight for height necessary for their maintenance or onset. Science 1974; 185: 949–51.
13. Bachmann KN, Schorr M, Bruno AG et al. Vertebral Volumetric Bone Density and Strength are Impaired in Women with Low-weight and Atypical Anorexia Nervosa. J Clin Endocrinol Metab 2017;102 (1): 57–68. DOI: 10.1210/jc.2016-2099
14. Chan JL, Mantzoros CS. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhea and anorexia nervosa. Lancet 2005; 366:
74.
15. Pinto S, Roseberry AG, Liu H. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 2004; 304 (5667): 110.
16. Peltz G, Aguirre MT, Sanderson M, Fadden MK. The role of fat mass index in determining obesity. Am J Hum Biol 2010; 22 (5), 639–47.
17. Warren IP, Ramos RH, Bronson E. Exercise-associated amenorrhea. Physician Sportsmed 2002; 30: 10.
18. Stokić E, Srdić B, Barak O. Body mass index, body fat mass and the occurrence of amenorrhea in ballet dancers. Gynecol Endocrinol 2005; 20 (4): 195–9.
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии
им. акад. В.И. Кулакова» Минздрава России, Москва, Россия
*doctor.dgusev@gmail.com
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Dmitry V. Gusev*, Sergey Yu. Kuznetsov, Tatyana Yu. Ivanets, Galina E. Chernukha
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*doctor.dgusev@gmail.com