Original Paper
HOR MON E RE SE ARCH I N PÆDIATRIC S
Received: October 29, 2012 Accepted: August 22, 2014 Published online: October 15, 2014
Horm Res Paediatr 2014;82:319–323 DOI: 10.1159/000367895
Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1 Louise Cominato a Mariana Moraes Xavier da Silva a Leandra Steinmetz a Vanessa Pinzon b Bacy Fleitlich-Bilyk b Durval Damiani a
a
Pediatric Endocrinology Unit, Children’s Institute, and b Psychiatry Institute, Teaching Hospital of the São Paulo University Medical School, São Paulo, Brazil
Key Words Anorexia nervosa · Insulin-like growth factor 1 · Menstrual cycle · Nutrition · EDNOS
tional recovery (p = 0.0001). At the resumption of menstruation, the patients showed IGF-1 levels >342.8 ng/ml. Conclusion: IGF-1 was the best predictor of the return of menses in female adolescents with AN or EDNOS. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 1663–2818/14/0825–0319$39.50/0 E-Mail [email protected] www.karger.com/hrp
Introduction
Eating disorders are multifactorial diseases that lead the patient to assume inadequate eating behaviors. In general, these disorders affect adolescents and young adults, particularly females, and are associated with high morbidity and mortality rates [1]. Accounts of eating disorders have appeared in medical literature since the 17th century, but medical interest in the subject has increased over the past few decades, as has the diagnosis and differentiation of eating disorders [1]. Anorexia nervosa (AN) is a serious multifactorial eating disorder. AN is characterized by the refusal to maintain an adequate minimum weight for the patient’s age and height, an intense fear of weight gain, disturbances in the perception of self-body image and amenorrhea, which arises due to severe malnutrition. Eating disorders not Louise Cominato Rua Simão Alvares, 51 Pinheiros, São Paulo, SP 05417030 (Brazil) E-Mail louise.cominato @ hotmail.com
Downloaded by: UCSF Library & CKM 169.230.243.252 - 12/8/2014 9:22:10 AM
Abstract Background: Follow-up visits of patients recovering from anorexia nervosa (AN) have shown that some patients do not resume menstrual cycles despite returning to the normal weight for their age and height. Aim: To verify whether leptin, insulin-like growth factor 1 (IGF-1) or another hormonal marker could be a good predictor of the return of menses. Patients and Methods: This prospective study included female adolescents diagnosed with AN or eating disorders not otherwise specified (EDNOS) and who were being treated in an ambulatory care unit during nutritional recovery. Body mass index and leptin, luteinizing hormone, estradiol and IGF-1 levels of these patients were evaluated. Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment. The hormone levels during nutritional recovery and at the time of the resumption of menses were analyzed. Results: The hormonal profiles improved after nutritional recovery, with IGF-1 correlating the most with the resumption of menses and nutri-
320
Horm Res Paediatr 2014;82:319–323 DOI: 10.1159/000367895
LH, are reportedly associated with recovery of menstruation [12–14]. However, this subject has not been completely investigated in the literature [14]. In this study, we sought to identify a hormonal parameter (leptin or other) that could predict the resumption of menses in patients with AN or EDNOS during nutritional recovery.
Patients and Methods This study was prospective and included females with eating disorders who were diagnosed and classified as exhibiting AN or EDNOS. The patients were diagnosed by psychiatrists affiliated with the Institute of Psychiatry of the Faculty of Medicine of the University of São Paulo and were diagnosed according to the DSM-IV criteria (online suppl. data; for all online suppl. material, see www.karger.com/doi/10.1159/000367895). Thirty-two adolescents with eating disorders were invited to take part in the study, which included the following inclusion criteria: a diagnosis of AN or EDNOS, female and amenorrheic. The exclusion criteria included male patients, girls with concomitant endocrine diseases or with other types of eating disorder such as bulimia nervosa, eumenorrheic patients or patients who abandoned the study. Four of the patients were excluded from the study due to noncompliance, while 6 patients were excluded for having menstrual cycles at the beginning of the study. Twenty-two adolescents aged between 12 and 16 years started the study. All of the patients were included in the study after informed consent was obtained from their guardians. All of the patients were provided with psychological and psychiatric support and nutritional guidance throughout the study (online suppl. data). Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment for the measurement of LH, FSH, prolactin, TSH, T3, T4, free T4, estradiol, leptin, GH and IGF-1 levels. The samples were analyzed by the Laboratory of Neurosciences – LIM 27 of the Institute of Psychiatry and Central Laboratory of the Teaching Hospital of the University of São Paulo using the following laboratory methods: LH, FSH, prolactin, TSH, T3, T4, free T4, GH and estradiol immunofluoroassay (Delfia; PerkinElmer); IGF-1 ELISA (DSL) and leptin-ELISA (LINCO Millipore). The patients’ body mass index (BMI), leptin, LH, estradiol and IGF-1 levels were compared at the beginning of the study and at the time of the resumption of the menstrual cycle. These parameters were also compared between the patients who exhibited menses and those patients who did not resume their menses during the study. WHO AnthroPlus software was used to determine IMC and Z-score percentiles [15]. SPSS-14 was used for the statistical analyses. A repeated-measures ANOVA was used to analyze the evolution of the parameters in the group of patients that menstruated and the group that did not menstruate over time. A model of proportional hazards was used for the analysis of the return of menstrual cycles. The Wilcoxon signed rank test was used for the analysis of the parameters upon the resumption of menses. A ROC curve was used to determine the cut-off point for the IGF-1 analysis pre- and post-menses to maximize the sensitivity and specificity of the analysis.
Cominato/da Silva/Steinmetz/Pinzon/ Fleitlich-Bilyk/Damiani
Downloaded by: UCSF Library & CKM 169.230.243.252 - 12/8/2014 9:22:10 AM
otherwise specified (EDNOS) is used to classify patients who do not meet all of the criteria for bulimia or anorexia. EDNOS is the main diagnosis among adolescents with eating disorders. Approximately 50% of patients develop all of the above symptoms, hence the importance of early diagnosis [2]. These patients exhibit hormonal changes that generally normalize with nutritional recovery. These changes in hormone levels most likely occur in an effort to conserve energy during the acute phase of the illness. Amenorrhea is the most frequent clinical complication of these female patients and occurs due to estrogen deficiency. Amenorrhea is linked to low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the absence of pulsatile LH secretion and decreased response to stimulation with gonadotropin-releasing hormone (GnRH) [3]. Menstrual cycle recovery is extremely important in the treatment of AN and EDNOS, as this outcome is a major indicator of therapeutic success [4]. For many decades it was believed that a threshold quantity of adipose tissue was essential for the onset of puberty [5]. Androgens are converted into estrogens in adipose tissue, and decreases in the level of this tissue contribute to hypoestrogenemia and reductions in positive feedback for LH secretion [6]. Leptin is a peptide hormone secreted by adipocytes in proportion to the amount of energy stored in fat. Leptin receptors are specifically expressed in GnRH-secreting neurons. The pulsatile secretion of this hypothalamic peptide accelerates in proportion to the stock of fat; in other words, the excessive loss of adipose tissue leads to the decreased production of leptin, which diminishes signals to the central nervous system, leading to a decrease in GnRH and a subsequent drop in LH and FSH levels. These changes consequently lead to hypogonadotropic hypogonadism [7–9]. The GH-IGF-1 axis is also associated with a patient’s nutritional condition, as malnourished patients exhibit reduced IGF-1 production. IGF-1 levels are low in patients with AN and rise with nutritional recovery. The GH levels in these patients may be normal, high or low [10]. Some female patients with AN present nutritional recovery but do not recover menstrual cycles. Some studies have attempted to identify the factors associated with the resumption of menses in eating disorders: Köpp et al. [11] and Ballauff et al. [12] demonstrated that leptin concentrations >1.85 ng/ml are necessary to increase LH levels to the minimum values required for the resumption of the menstrual cycle. Other hormones, such as cortisol and
BMI, kg/m2 Leptin Estradiol LH IGF-1
Beginning of the study
At menses
p
16.07±1.4 3.9±4.9 15.4±20.4 3.9±4.8 295.3±100
18.8±1.2 5.1±3.5 76.3±90 17.1±25 407.3±117
0.03* 0.32 0.008* 0.026* 0.05*
* p < 0.05.
Results
During the 20-week study, the patients showed significant nutritional improvement and recovery of hormone levels. Mean BMI, LH and IGF-1 between the beginning of the study and at the resumption of menses were increased significantly (p ≤ 0.05; table 1). FSH, prolactin, GH, TSH and thyroid hormone measurements are not shown because the levels of these hormones did not change significantly during the study. All patients presented with secondary amenorrhea at the beginning of the study. The hypothalamic-pituitarygonadal axis was reactivated in 13 of these patients (59%). All of these patients had had menstrual cycles for more than 1 year before experiencing amenorrhea due to an eating disorder. The majority of these patients regained their menstrual cycles at BMIs between the 25th and 50th percentiles (64%). Two of the patients menstruated with BMIs between the 50th and 75th percentiles, and 3 of the patients menstruated with BMIs between the 10th and 25th percentiles (table 2). The average time required for menstruation to return was 5 months. During the 20 weeks of the study, the patients’ BMI (p < 0.001), leptin (p = 0.01), IGF-1 (p < 0.001) and estradiol (p = 0.021) levels increased significantly. Only IGF-1 showed a significant difference between the group of patients who resumed their cycles and those patients who did not resume their cycles (tables 3, 4). The majority of patients had IGF-1 levels >342.8 ng/ml when menses resumed (Z-score: –0.3), sensitivity 0.92/specificity 0.76 (fig. 1a, b).
Discussion
Our study showed good nutritional recovery of the AN and EDNOS patients, with increases in BMI observed in all cases. The majority of these patients resumed their Menses and IGF-1 in Anorexia Nervosa
Table 2. Z-scores for BMI and IGF-1 in patients with AN or
EDNOS at the resumption of menses Patient
Z-score BMI
IGF-1, ng/ml
Z-score IGF-1
1 2 3 4 5 6 7 8 9 10 11 12 13
–1.81 –1.15 –0.84 –0.52 –0.3 –0.64 0.69 –1.73 –1.29 –1.62 –0.49 0.21 –0.15
427.5 527.7 460.3 469.5 420.5 332.2 491.7 458.5 317 473.1 345.2 468.9 352.2
–0.09 0.43 –0.03 0.01 –0.2 –0.61 1.12 0.11 –0.7 0.03 –0.53 0.44 –0.49
Spearman correlation between BMI-SDS and IGF-1-SDS is r2 = 0.12 (p = 0.2).
Table 3. Differences between the 1st and 20th weeks of the study for BMI and hormonal parameters (mean ± SD)
BMI, kg/m2 Leptin IGF-1 LH Estradiol
1st week
20th week
p
16.07±1.4 3.9±4.9 295.3±100 3.9±4.8 15.4±20.4
18.9±0.7 11.8±7.6 386.6±44.3 6.8±3.2 52.3±26
342.8 ng/ml when menses resumed. Few studies have investigated the hormonal changes related to the return of the menstrual cycle [7, 12]. Only one study observed the hormonal changes that occur at
Menses and IGF-1 in Anorexia Nervosa
11 Köpp W, Blum WF, von Prittwitz S, Ziegler A, Lübbert H, Emons G, Herzog W, Herpertz S, Deter HC, Remschmidt H, Hebebrand J: Low leptin levels predict amenorrhea in underweight and eating disordered females. Mol Psychiatry 1997;2:335–340. 12 Ballauff A, Ziegler A, Emons G, Sturm G, Blum WF, Remschmidt H, Hebebrand J: Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain. Mol Psychiatry 1999;4:71–75. 13 Arimura C, Nozaki T, Takakura S, Kawai K, Takii M, Sudo N, Kubo C: Predictors of menstrual resumption by patients with anorexia nervosa. Eat Weight Disord 2010; 15: 226– 233.
14 Misra M, Prabhakaran R, Miller KK, Tsai P, Lin A, Lee N, Herzog DB, Klibanski A: Role of cortisol in menstrual recovery in adolescents girl with anorexia nervosa Pediatr Res 2006; 59:598–603. 15 World Health Organization: AnthroPlus (computer program). Version 1.0.4. Geneva, WHO, 2007. 16 Golden NH, Jacobs MS, Sterling WM, Hertz S: Treatment goal weight in adolescents with anorexia nervosa: use of BMI percentiles. Int J Eating Disord 2008;41:301–306. 17 Di Carlo C, Tommaselli GA, De Filippo E, Pisano G, Nasti A, Bifulco G, Contaldo F, Nappi C: Menstrual status and serum leptin levels in anorexic and in menstruating women with low body mass indexes. Fertil Steril 2002; 78: 376–382. 18 Golden NH, Jacobson MS, Schebendach J, Solanto MV, Hertz SM, Shenker IR: Resumption of menses in anorexia nervosa. Arch Pediatr Adolesc Med 1997;151:16–21.
Horm Res Paediatr 2014;82:319–323 DOI: 10.1159/000367895
323
Downloaded by: UCSF Library & CKM 169.230.243.252 - 12/8/2014 9:22:10 AM
7 Khan SM, Hamnvik OP, Brinkoetter M, Mantzoros CS: Leptin as a modulator of neuroendocrine function in humans. Yonsei Med J 2012;53:671–679. 8 Hebebrand J, Muller TD, Holtkamp K, Herpetz-Dahlmann B: The role of leptin in anorexia nervosa: clinical implications. Mol Psychiatry 2007;12:23–35. 9 Audi L, Mantzoros CS, Vidal-Puig A, Vargas D, Gussinye M, Carrascosa A: Leptin in relation to resumption of menses in women with anorexia nervosa. Mol Psychiatry 1998; 3: 544–547. 10 Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, Ott M, Herzog DB, Johnson ML, Klibanski A: Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab 2003;88:5615–5623.
HOR MON E RE SE ARCH I N PÆDIATRIC S
Received: October 29, 2012 Accepted: August 22, 2014 Published online: October 15, 2014
Horm Res Paediatr 2014;82:319–323 DOI: 10.1159/000367895
Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1 Louise Cominato a Mariana Moraes Xavier da Silva a Leandra Steinmetz a Vanessa Pinzon b Bacy Fleitlich-Bilyk b Durval Damiani a
a
Pediatric Endocrinology Unit, Children’s Institute, and b Psychiatry Institute, Teaching Hospital of the São Paulo University Medical School, São Paulo, Brazil
Key Words Anorexia nervosa · Insulin-like growth factor 1 · Menstrual cycle · Nutrition · EDNOS
tional recovery (p = 0.0001). At the resumption of menstruation, the patients showed IGF-1 levels >342.8 ng/ml. Conclusion: IGF-1 was the best predictor of the return of menses in female adolescents with AN or EDNOS. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 1663–2818/14/0825–0319$39.50/0 E-Mail [email protected] www.karger.com/hrp
Introduction
Eating disorders are multifactorial diseases that lead the patient to assume inadequate eating behaviors. In general, these disorders affect adolescents and young adults, particularly females, and are associated with high morbidity and mortality rates [1]. Accounts of eating disorders have appeared in medical literature since the 17th century, but medical interest in the subject has increased over the past few decades, as has the diagnosis and differentiation of eating disorders [1]. Anorexia nervosa (AN) is a serious multifactorial eating disorder. AN is characterized by the refusal to maintain an adequate minimum weight for the patient’s age and height, an intense fear of weight gain, disturbances in the perception of self-body image and amenorrhea, which arises due to severe malnutrition. Eating disorders not Louise Cominato Rua Simão Alvares, 51 Pinheiros, São Paulo, SP 05417030 (Brazil) E-Mail louise.cominato @ hotmail.com
Downloaded by: UCSF Library & CKM 169.230.243.252 - 12/8/2014 9:22:10 AM
Abstract Background: Follow-up visits of patients recovering from anorexia nervosa (AN) have shown that some patients do not resume menstrual cycles despite returning to the normal weight for their age and height. Aim: To verify whether leptin, insulin-like growth factor 1 (IGF-1) or another hormonal marker could be a good predictor of the return of menses. Patients and Methods: This prospective study included female adolescents diagnosed with AN or eating disorders not otherwise specified (EDNOS) and who were being treated in an ambulatory care unit during nutritional recovery. Body mass index and leptin, luteinizing hormone, estradiol and IGF-1 levels of these patients were evaluated. Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment. The hormone levels during nutritional recovery and at the time of the resumption of menses were analyzed. Results: The hormonal profiles improved after nutritional recovery, with IGF-1 correlating the most with the resumption of menses and nutri-
320
Horm Res Paediatr 2014;82:319–323 DOI: 10.1159/000367895
LH, are reportedly associated with recovery of menstruation [12–14]. However, this subject has not been completely investigated in the literature [14]. In this study, we sought to identify a hormonal parameter (leptin or other) that could predict the resumption of menses in patients with AN or EDNOS during nutritional recovery.
Patients and Methods This study was prospective and included females with eating disorders who were diagnosed and classified as exhibiting AN or EDNOS. The patients were diagnosed by psychiatrists affiliated with the Institute of Psychiatry of the Faculty of Medicine of the University of São Paulo and were diagnosed according to the DSM-IV criteria (online suppl. data; for all online suppl. material, see www.karger.com/doi/10.1159/000367895). Thirty-two adolescents with eating disorders were invited to take part in the study, which included the following inclusion criteria: a diagnosis of AN or EDNOS, female and amenorrheic. The exclusion criteria included male patients, girls with concomitant endocrine diseases or with other types of eating disorder such as bulimia nervosa, eumenorrheic patients or patients who abandoned the study. Four of the patients were excluded from the study due to noncompliance, while 6 patients were excluded for having menstrual cycles at the beginning of the study. Twenty-two adolescents aged between 12 and 16 years started the study. All of the patients were included in the study after informed consent was obtained from their guardians. All of the patients were provided with psychological and psychiatric support and nutritional guidance throughout the study (online suppl. data). Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment for the measurement of LH, FSH, prolactin, TSH, T3, T4, free T4, estradiol, leptin, GH and IGF-1 levels. The samples were analyzed by the Laboratory of Neurosciences – LIM 27 of the Institute of Psychiatry and Central Laboratory of the Teaching Hospital of the University of São Paulo using the following laboratory methods: LH, FSH, prolactin, TSH, T3, T4, free T4, GH and estradiol immunofluoroassay (Delfia; PerkinElmer); IGF-1 ELISA (DSL) and leptin-ELISA (LINCO Millipore). The patients’ body mass index (BMI), leptin, LH, estradiol and IGF-1 levels were compared at the beginning of the study and at the time of the resumption of the menstrual cycle. These parameters were also compared between the patients who exhibited menses and those patients who did not resume their menses during the study. WHO AnthroPlus software was used to determine IMC and Z-score percentiles [15]. SPSS-14 was used for the statistical analyses. A repeated-measures ANOVA was used to analyze the evolution of the parameters in the group of patients that menstruated and the group that did not menstruate over time. A model of proportional hazards was used for the analysis of the return of menstrual cycles. The Wilcoxon signed rank test was used for the analysis of the parameters upon the resumption of menses. A ROC curve was used to determine the cut-off point for the IGF-1 analysis pre- and post-menses to maximize the sensitivity and specificity of the analysis.
Cominato/da Silva/Steinmetz/Pinzon/ Fleitlich-Bilyk/Damiani
Downloaded by: UCSF Library & CKM 169.230.243.252 - 12/8/2014 9:22:10 AM
otherwise specified (EDNOS) is used to classify patients who do not meet all of the criteria for bulimia or anorexia. EDNOS is the main diagnosis among adolescents with eating disorders. Approximately 50% of patients develop all of the above symptoms, hence the importance of early diagnosis [2]. These patients exhibit hormonal changes that generally normalize with nutritional recovery. These changes in hormone levels most likely occur in an effort to conserve energy during the acute phase of the illness. Amenorrhea is the most frequent clinical complication of these female patients and occurs due to estrogen deficiency. Amenorrhea is linked to low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the absence of pulsatile LH secretion and decreased response to stimulation with gonadotropin-releasing hormone (GnRH) [3]. Menstrual cycle recovery is extremely important in the treatment of AN and EDNOS, as this outcome is a major indicator of therapeutic success [4]. For many decades it was believed that a threshold quantity of adipose tissue was essential for the onset of puberty [5]. Androgens are converted into estrogens in adipose tissue, and decreases in the level of this tissue contribute to hypoestrogenemia and reductions in positive feedback for LH secretion [6]. Leptin is a peptide hormone secreted by adipocytes in proportion to the amount of energy stored in fat. Leptin receptors are specifically expressed in GnRH-secreting neurons. The pulsatile secretion of this hypothalamic peptide accelerates in proportion to the stock of fat; in other words, the excessive loss of adipose tissue leads to the decreased production of leptin, which diminishes signals to the central nervous system, leading to a decrease in GnRH and a subsequent drop in LH and FSH levels. These changes consequently lead to hypogonadotropic hypogonadism [7–9]. The GH-IGF-1 axis is also associated with a patient’s nutritional condition, as malnourished patients exhibit reduced IGF-1 production. IGF-1 levels are low in patients with AN and rise with nutritional recovery. The GH levels in these patients may be normal, high or low [10]. Some female patients with AN present nutritional recovery but do not recover menstrual cycles. Some studies have attempted to identify the factors associated with the resumption of menses in eating disorders: Köpp et al. [11] and Ballauff et al. [12] demonstrated that leptin concentrations >1.85 ng/ml are necessary to increase LH levels to the minimum values required for the resumption of the menstrual cycle. Other hormones, such as cortisol and
BMI, kg/m2 Leptin Estradiol LH IGF-1
Beginning of the study
At menses
p
16.07±1.4 3.9±4.9 15.4±20.4 3.9±4.8 295.3±100
18.8±1.2 5.1±3.5 76.3±90 17.1±25 407.3±117
0.03* 0.32 0.008* 0.026* 0.05*
* p < 0.05.
Results
During the 20-week study, the patients showed significant nutritional improvement and recovery of hormone levels. Mean BMI, LH and IGF-1 between the beginning of the study and at the resumption of menses were increased significantly (p ≤ 0.05; table 1). FSH, prolactin, GH, TSH and thyroid hormone measurements are not shown because the levels of these hormones did not change significantly during the study. All patients presented with secondary amenorrhea at the beginning of the study. The hypothalamic-pituitarygonadal axis was reactivated in 13 of these patients (59%). All of these patients had had menstrual cycles for more than 1 year before experiencing amenorrhea due to an eating disorder. The majority of these patients regained their menstrual cycles at BMIs between the 25th and 50th percentiles (64%). Two of the patients menstruated with BMIs between the 50th and 75th percentiles, and 3 of the patients menstruated with BMIs between the 10th and 25th percentiles (table 2). The average time required for menstruation to return was 5 months. During the 20 weeks of the study, the patients’ BMI (p < 0.001), leptin (p = 0.01), IGF-1 (p < 0.001) and estradiol (p = 0.021) levels increased significantly. Only IGF-1 showed a significant difference between the group of patients who resumed their cycles and those patients who did not resume their cycles (tables 3, 4). The majority of patients had IGF-1 levels >342.8 ng/ml when menses resumed (Z-score: –0.3), sensitivity 0.92/specificity 0.76 (fig. 1a, b).
Discussion
Our study showed good nutritional recovery of the AN and EDNOS patients, with increases in BMI observed in all cases. The majority of these patients resumed their Menses and IGF-1 in Anorexia Nervosa
Table 2. Z-scores for BMI and IGF-1 in patients with AN or
EDNOS at the resumption of menses Patient
Z-score BMI
IGF-1, ng/ml
Z-score IGF-1
1 2 3 4 5 6 7 8 9 10 11 12 13
–1.81 –1.15 –0.84 –0.52 –0.3 –0.64 0.69 –1.73 –1.29 –1.62 –0.49 0.21 –0.15
427.5 527.7 460.3 469.5 420.5 332.2 491.7 458.5 317 473.1 345.2 468.9 352.2
–0.09 0.43 –0.03 0.01 –0.2 –0.61 1.12 0.11 –0.7 0.03 –0.53 0.44 –0.49
Spearman correlation between BMI-SDS and IGF-1-SDS is r2 = 0.12 (p = 0.2).
Table 3. Differences between the 1st and 20th weeks of the study for BMI and hormonal parameters (mean ± SD)
BMI, kg/m2 Leptin IGF-1 LH Estradiol
1st week
20th week
p
16.07±1.4 3.9±4.9 295.3±100 3.9±4.8 15.4±20.4
18.9±0.7 11.8±7.6 386.6±44.3 6.8±3.2 52.3±26
342.8 ng/ml when menses resumed. Few studies have investigated the hormonal changes related to the return of the menstrual cycle [7, 12]. Only one study observed the hormonal changes that occur at
Menses and IGF-1 in Anorexia Nervosa
11 Köpp W, Blum WF, von Prittwitz S, Ziegler A, Lübbert H, Emons G, Herzog W, Herpertz S, Deter HC, Remschmidt H, Hebebrand J: Low leptin levels predict amenorrhea in underweight and eating disordered females. Mol Psychiatry 1997;2:335–340. 12 Ballauff A, Ziegler A, Emons G, Sturm G, Blum WF, Remschmidt H, Hebebrand J: Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain. Mol Psychiatry 1999;4:71–75. 13 Arimura C, Nozaki T, Takakura S, Kawai K, Takii M, Sudo N, Kubo C: Predictors of menstrual resumption by patients with anorexia nervosa. Eat Weight Disord 2010; 15: 226– 233.
14 Misra M, Prabhakaran R, Miller KK, Tsai P, Lin A, Lee N, Herzog DB, Klibanski A: Role of cortisol in menstrual recovery in adolescents girl with anorexia nervosa Pediatr Res 2006; 59:598–603. 15 World Health Organization: AnthroPlus (computer program). Version 1.0.4. Geneva, WHO, 2007. 16 Golden NH, Jacobs MS, Sterling WM, Hertz S: Treatment goal weight in adolescents with anorexia nervosa: use of BMI percentiles. Int J Eating Disord 2008;41:301–306. 17 Di Carlo C, Tommaselli GA, De Filippo E, Pisano G, Nasti A, Bifulco G, Contaldo F, Nappi C: Menstrual status and serum leptin levels in anorexic and in menstruating women with low body mass indexes. Fertil Steril 2002; 78: 376–382. 18 Golden NH, Jacobson MS, Schebendach J, Solanto MV, Hertz SM, Shenker IR: Resumption of menses in anorexia nervosa. Arch Pediatr Adolesc Med 1997;151:16–21.
Horm Res Paediatr 2014;82:319–323 DOI: 10.1159/000367895
323
Downloaded by: UCSF Library & CKM 169.230.243.252 - 12/8/2014 9:22:10 AM
7 Khan SM, Hamnvik OP, Brinkoetter M, Mantzoros CS: Leptin as a modulator of neuroendocrine function in humans. Yonsei Med J 2012;53:671–679. 8 Hebebrand J, Muller TD, Holtkamp K, Herpetz-Dahlmann B: The role of leptin in anorexia nervosa: clinical implications. Mol Psychiatry 2007;12:23–35. 9 Audi L, Mantzoros CS, Vidal-Puig A, Vargas D, Gussinye M, Carrascosa A: Leptin in relation to resumption of menses in women with anorexia nervosa. Mol Psychiatry 1998; 3: 544–547. 10 Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, Ott M, Herzog DB, Johnson ML, Klibanski A: Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab 2003;88:5615–5623.
