- Email: [email protected]
Return of Menses in Previously Overweight Patients with Eating Disorders
Journal Pre-proof Return of Menses in Previously Overweight Patients with Eating Disorders Radhika Rastogi, BA, Erin H. Sieke, MD MS, Alexa Nahra, Julia Sabik, Ellen S. Rome, MD MPH PII:
S1083-3188(19)30353-5
DOI:
https://doi.org/10.1016/j.jpag.2019.11.002
Reference:
PEDADO 2417
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 24 June 2019 Revised Date:
2 October 2019
Accepted Date: 4 November 2019
Please cite this article as: Rastogi R, Sieke EH, Nahra A, Sabik J, Rome ES, Return of Menses in Previously Overweight Patients with Eating Disorders, Journal of Pediatric and Adolescent Gynecology (2019), doi: https://doi.org/10.1016/j.jpag.2019.11.002. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc. on behalf of North American Society for Pediatric and Adolescent Gynecology.
Return of Menses in Previously Overweight Patients with Eating Disorders Radhika Rastogi BA1, Erin H. Sieke MD MS2, Alexa Nahra3, Julia Sabik3, Ellen S. Rome MD MPH3
Affiliations: 1Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9501 Euclid Avenue/EC 10, Cleveland, OH 44195, USA 2
The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, 9NW56, Philadelphia,
PA, 19104, USA 3
Department of General Pediatrics and Adolescent Medicine, Cleveland Clinic Children’s
Hospital, 9500 Euclid Ave/R3, Cleveland, OH 44195, USA
Study Institution: Department of General Pediatrics and Adolescent Medicine, Cleveland Clinic Children’s Hospital Funding: None. Disclaimers: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. Corresponding author contact information: Radhika Rastogi Telephone: 914-772-3963 Email Address: [email protected]
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Abstract: Study objective: Adolescents with eating disorders and a history of overweight present with higher weights, longer duration of disease, but equally severe symptomatology compared to previously normal weight patients. To better delineate treatment goals for this understudied population, we compared weight at menses resumption to premorbid maximum weight among previously overweight and normal weight patients. Design: Retrospective cohort study. Setting: Outpatient adolescent medicine clinic at an eating disorder referral center. Participants: Postmenarchal patients meeting criteria for DSM 5 eating disorders. History of overweight was defined as a BMI ≥ 85th percentile or ≥ 25. Main Outcome Measures: Weight characteristics at presentation and menses resumption (BMI, BMI z-score, change from maximum weight to presentation weight) Results: Previously overweight patients presented with greater mean weight, longer duration of disease and higher BMI than previously normal weight patients. No difference was found in rates of amenorrhea at presentation or menses resumption. Previously overweight patients resumed menses at a younger age and higher BMI z-score. Difference between weight at menses resumption and premorbid maximum weight was greater for previously overweight patients. Conclusions: Previously overweight patients with eating disorders present differently than their normal weight peers, so reliance on weight status as a screening criteria may result in underdiagnosis. Though BMI z-scores associated with menses resumption are higher for 2
previously overweight patients, there is no difference in weight gain between presentation and menses resumption and time to menses resumption compared to previously normal weight patients. Moreover, menses resumption occurred at weights significantly lower than premorbid maximum weight for previously overweight patients, so restoration to highest premorbid weight is not necessary. Keywords: Eating disorders, Eating and Feeding disorders, Anorexia Nervosa, Menstruation Disturbance
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Introduction The rising prevalence of adolescent overweight and obesity has resulted in an emphasis on weight loss by clinicians and health education curricula. Likely reflecting this messaging, overweight adolescents report greater body dissatisfaction and concern about weight than normal weight adolescents.1 These risk factors result in a higher likelihood of eating disorder thoughts and behaviors such as bingeing, purging, diet pill and laxative use among these patients.1–4 The reported prevalence of a history of overweight or obesity among pediatric patients with eating disorders ranges from 11-36%.5–7 Previously overweight adolescents with eating disorders present differently than their previously normal-weight peers. Specifically, they present with greater weight suppression (difference between premorbid highest weight and presentation weight), longer duration of disease, higher body mass index (BMI).6,8 However, despite no difference in symptomatology, including comparable rates of amenorrhea and with similar scores on psychological measures, previously overweight adolescents with eating disorders are less likely to be hospitalized.6,8 Patients with eating disorders, including anorexia nervosa, atypical anorexia nervosa, avoidant/restrictive food intake disorder, and bulimia nervosa, can present with both primary and secondary amenorrhea.9 Amenorrhea is associated with comorbidities such as lower peak bone mass and impaired neuropsychological functioning; resumption of menses is a well-established marker of physiologic recovery among patients with eating disorders.10,11 In a previous study, previously overweight adolescents with secondary amenorrhea resumed menses at a significantly higher weight than their previously normal weight peers, suggesting that goal recovery weights may differ based on premorbid overweight status.7
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There remains a paucity of longitudinal data on cohorts of previously overweight patients. Given that previous weight status may impact treatment goal weights, comparison between premorbid maximum weight and weight at menses resumption is necessary. Further, there is lack of literature on incidence of history of overweight as well as amenorrhea and subsequent return of menses in patients with bulimia nervosa and avoidant/restrictive food intake disorder (ARFID), since prior studies have focused their investigation exclusively on patients with anorexia nervosa and atypical anorexia nervosa. To address these gaps in knowledge, we aimed to investigate the differences in presenting characteristics, including 1. eating disorder diagnosis, 2. weight status, 3. weight suppression, and 4. duration of disease between patients with eating disorders with and without a history of overweight. We also compared menstrual characteristics, including 1. rates of secondary amenorrhea and 2. weight status at menses resumption between the groups. In keeping with the prior literature, we hypothesized that previously overweight patients would present at higher weights but with greater weight suppression and longer duration of illness with no differences in rates of amenorrhea. We further hypothesized that previously overweight patients would resume menses at higher weights than previously normal weight patients.
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Methods Study population A retrospective longitudinal cohort study was conducted on female patients hospitalized and followed in outpatient clinic for nutritional insufficiency at the Cleveland Clinic, an academic medical center, between January 2008 and January 2017 (n=420). Data were collected from the electronic medical record for up to 5 years or until the last documented clinic visit from the time of hospitalization. Inclusion criteria included female sex, presentation for evaluation of nutritional insufficiency and care by an adolescent medicine physician, so patients with a wide age range were included. Exclusion criteria included premenarchal status at presentation, nutritional insufficiency secondary to a non-eating disorder diagnosis, and missing data on presentation characteristics. Patients on hormonal contraception at presentation or follow up were excluded from analysis on menstrual characteristics, but included in the analysis on presentation characteristics. The study protocol was approved by the Cleveland Clinic Institutional Review Board. Eating disorder diagnoses of anorexia nervosa, bulimia nervosa, other specified feeding or eating disorder (specifically atypical anorexia), and ARFID were assigned by adolescent medicine specialists based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM 5) criteria. For patients seen before 2013, diagnoses were retrospectively assigned based on the DSM 5 criteria by an adolescent medicine physician knowledgeable about the patient’s history. BMI at maximum weight was calculated based on self-reported maximum weight, height at maximum weight, and age at maximum weight prior to presentation, as previously described in other published studies.7,8 History of overweight was defined as a BMI 6
≥85th percentile for those younger than 20 years, and a BMI ≥ 25 for those 20 years or older at maximum weight. History of normal weight was defined as BMI between 5th and 85th percentile at age <20 years and BMI between 18.5 and 25 at age ≥ 20 years at maximum weight. Secondary amenorrhea was defined as absence of menses for at least 3 months among postmenarchal patients.12 Return of menses was based on self-report of at least 1 month of menses at follow up visits for all patients.7 Weight and height at resumption of menses were collected from the closest office or inpatient visit following reported date of return of menses. Measures Age, race/ethnicity, duration of illness, anthropometric measures (height, weight), menstrual status, and hormonal contraceptive use were collected at presentation and follow-up visits. Patients were weighed on a scale in a hospital gown after voiding. Patients were blinded to their weights. Heights were obtained on a standard stadiometer. Heights and weights are obtained by the same eating disorder nursing team. Weight of menses resumption was taken from the closest office visit subsequent to the reported date of resumption which varied from days to months. BMI percentiles and z-scores were calculated for patients younger than 20 years based on the Centers for Disease Control and Prevention growth charts.13 Weight suppression was calculated as the difference between maximum weight and presentation weight, both in absolute numbers (kilograms) and in percent of maximum weight. Similarly, BMI suppression, BMI percentile suppression, and BMI z-score suppression were calculated as the difference between the measures at maximum weight and presentation. Statistical Analysis
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The primary outcome of interest was the difference in weight status among previously overweight and previously normal weight patients at time of presentation and at return of menses. Menses resumption analysis was limited to patients who were amenorrheic at presentation and had follow up menstrual data available. All variables were assessed for normality of distribution. Bivariate analyses were used to compare presentation and follow up data. Independent t tests were used to compare continuous variables and chi square analyses were used to compare categorical variables. Data are described as means with standard deviations for continuous variables and counts and counts with percentages for categorical variables. Significance was established a priori at an α level of 0.05. Statistical analyses were conducted on STATA version 14 (Stata Inc., Plano TX).
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Results Presentation Characteristics Of the 420 female patients who presented for evaluation of nutritional insufficiency between 2008-2017, 114 did not qualify: 5 had diagnoses other than an eating disorder, 41 were premenarchal, 7 were underweight at their maximum weight, and 61 had missing presentation data. A total of 306 patients were included in the study. Of these, 31% of patients had a history of overweight. Patient demographics and diagnoses are presented in Table 1. A greater proportion of the previously overweight patients were diagnosed with atypical anorexia or bulimia nervosa whereas more previously normal weight patients were diagnosed with anorexia nervosa or ARFID. Mean duration of disease prior to presentation was longer in the previously overweight group. Weight characteristics at maximum weight and presentation are compared in Table 2. BMI at presentation was higher among the previously overweight group. Weight suppression, both in absolute amount and relative to maximum weight, was greater in previously overweight patients. Weight characteristics also differed by DSM 5 diagnosis. Mean maximum BMI was higher among patients with atypical anorexia or bulimia nervosa (26.4 kg/m2 ± 5.5 and 26.4 kg/m2 ± 4.4) as compared to patients with anorexia nervosa or ARFID (22.7 kg/m2 ± 3.9 and 21.6 kg/m2 ± 3.2) (p<0.001). Maximum weights differed similarly, with patients with atypical anorexia or bulimia nervosa having a higher maximum weight (69.9kg ±14.2 and 71.5kg ± 12.5) than patients with anorexia nervosa or ARFID (60.4kg ± 11.1 and 56kg ± 7.8) (p<0.001). At 9
presentation, patients with anorexia nervosa and ARFID presented with lower BMIs (17.8 kg/m2 ± 2.1 and 17.53 kg/m2 ± 2.7) than patients with atypical anorexia or bulimia nervosa (22.5 kg/m2 ± 3.6 and 23.6 kg/m2 ± 3.2) (p<0.001). Presentation weights followed a similar pattern, with patients with anorexia nervosa or ARFID weighing less at presentation (47.6kg ± 6.4 and 46.0kg ± 7.8) than patients with atypical anorexia or bulimia nervosa (60.2kg ± 10.9 and 64kg ± 11.1) (p<0.001). Lastly, weight suppression was greatest among patients with anorexia nervosa (12.8kg ± 10.1), comparable among those with ARFID and atypical anorexia (9.9kg ± 6.8 and 9.7kg ± 9.7), and lowest among patients with bulimia nervosa (7.5kg ± 10) (p=0.016). Menstrual Characteristics Rates of amenorrhea at presentation were comparable between previously normal and previously overweight patients (75 (35.9%) vs. 43 (44%), p=0.34). Four patients were excluded from menses resumption analysis as they were on hormonal contraception at follow up. Menstrual characteristics at follow up are presented in Table 3. Though less than ⅓ of patients had follow up, rates of follow up did not differ between patients with and without a history of overweight (28.2% vs. 27.8%, p = 1.0). Rates of follow up differed by diagnosis with 67 (33%) patients with anorexia nervosa, 8 (21%) patients with atypical anorexia nervosa, 10 (27%) patients with ARFID, and 1 (4%) patient with bulimia nervosa having follow up data (p=0.01). Of the 59 previously normal weight patients who had follow up data, 40 (67.7%) resumed menses, 18 (30.5%) continued to be amenorrheic, and 1 (1.7%) was on hormonal contraception. Of the 27 previously overweight patients with follow up data, 19 (70.3%) resumed menses, 5 (18.5%) continued to be amenorrheic, and 3 (11.1%) were on hormonal contraception. There were no differences in menstrual status at follow up between patients with and without a history 10
of overweight (p=0.09). Time between menses resumption and weight measurement did not differ by study group (5.5 ±7.3 months vs. 4.1 ± 5.1, p=0.44). Previously overweight patients resumed menses at a younger age and higher BMI z-score than their normal-weight peers. There was no difference in time between presentation and resumption of menses between the groups (p=0.17). Previously normal weight patients resumed menses closer to their maximum weight than previously overweight patients did. Other characteristics, including rates of amenorrhea at presentation, duration of amenorrhea, menstrual status at follow up, and weight gain from presentation to menses resumption did not differ by study group. Menstrual status did not differ by DSM 5 diagnosis Though rates of follow up did not differ by study group, since less than 1/3 of patients were included in follow up analysis, we compared patients with and without follow up to identify sources of bias. Compared to patients without follow up, patients with follow up reported maximum weight at a younger age (15.1 ± 2.5 years vs. 15.9 ± 2.7 years, p=0.01). Maximum weight, BMI, BMI percentiles, and BMI z-scores at maximum weight did not differ. Patients with follow up presented at a younger age (17.2 ±2.9 years vs. 18.1 ± 3.0, p=0.010), lower weight (46.7 ± 8.1 kg vs. 51.8 ± 10.0 kg, p<0.001), BMI (17.5 ± 3 vs. 19.3 ± 3.3, p=0.007), BMI percentile (15.8 ± 20.7 vs. 32.1 ± 29.8, p<0.001), and BMI z-score (-1.58 ± 1.34 vs. -0.87 ± 1.45, p<0.001). Follow up patients had fewer months of disease (18.0 ± 19.4 vs. 34.3 ± 38.8, p<0.001) with greater weight suppression (13.5 ± 7.5 kg vs. 10.9 ± 10.5 kg, p=0.033). Patients with follow up were more likely to have anorexia nervosa (77.9% vs. 62.3%) and less likely to have atypical anorexia nervosa (9.3% vs. 13.6%), ARFID (11.6% vs. 12.3%), and bulimia nervosa (1.2% vs. 11.8%) (p=0.011).
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Discussion We found that 31% of the patients presenting for treatment of eating disorders had a history of overweight. They presented at higher weight status, but with greater weight suppression, and longer duration of disease than their previously normal weight peers. They were more likely to be diagnosed with atypical anorexia or bulimia nervosa than their previously normal weight peers. Although the rates of amenorrhea at presentation and menses resumption did not differ by group, previously overweight patients resumed menses at a younger age and a higher BMI z-score than their previously normal weight peers. Further, previously normal weight patients resumed menses at a weight significantly closer to their maximum weight than did previously overweight patients. Our findings of differences in the initial presentation between the two study groups are consistent with and validate previously reported presentation characteristics of this patient population.6 Our findings of greater disease duration and weight suppression among patients with premorbid overweight provides additional evidence of bias against timely identification of eating disorder symptoms in these patients. Therefore, our findings and those of prior studies likely underestimate the true burden of eating disorders among overweight or previously overweight adolescents as many of them do not achieve underweight status despite significant weight loss and thus may not be screened for eating disorders.6,8 In keeping with previous findings, we also report no differences between rates of amenorrhea at presentation and menses resumption between the two groups.6 Interestingly, our previously overweight patients presented with significantly greater weight suppression, which has been associated with worse symptomatology, such as higher rates of amenorrhea, regardless 12
of BMI.14 The mechanisms behind amenorrhea secondary to nutritional insufficiency are complex and involve degree of weight suppression, body fat mass, and levels of hormones including gonadotropins and leptin.15,16 Weight loss disrupts the hypothalamic-pituitary-ovarian (HPO) axis by altering the pulsatility of gonadotropin releasing hormone (GnRH), which maintains normal menstrual function by modulating estrogen levels.17 This relationship is mediated by neurotrophic hormones such as leptin and IGF-1, which regulate the function of GnRH releasing neurons.18,19 Both leptin and IGF-1 levels correlate with fat mass.17,20,21 Weight loss with relative sparing of fat mass in malnourished young women with disordered eating has been associated with preservation of regular menstrual function.21 Thus, in our previously overweight population, comparably higher fat mass at presentation may protect against the degree of menstrual disturbance that would have been expected given their degree of weight suppression compared to their normal weight peers. Our results significantly further prior literature by comparing maximum weight to weight at return of menses in a longitudinal cohort. This comparison is clinically relevant given the lack of guidelines addressing goals of weight restoration during treatment among previously overweight patients.22 Without guidelines, there is variation in approaches to weight restoration, as some clinicians rely on population-based “ideal body weight”, derived from sources such as the Metropolitan Life Insurance Company, whereas others seek to restore premorbid weight.23 An earlier study recommended treatment weight goals should target the 14th-39th BMI percentile.22 However, unlike our previously overweight patients who presented with normal or overweight status, this study’s population was underweight at presentation and there was no evaluation of pre-morbid weight status.22 In comparison, we found that menses resumed at higher BMI percentiles and %ideal body weight than those reported before, independent of 13
premorbid weight status.11 This difference may reflect differences in age at presentation and menses resumption, as our population was older with more years postmenarche. That previously normal weight patients in our cohort resumed menses at an average of 2kg below their maximum weight whereas previously overweight patients resumed menses at an average of 11kg below their maximum weight suggests that restoration to premorbid maximum weight is not necessary for physiologic restoration. Indeed, regardless of premorbid weight status, we found evidence of physiologic recovery through return of menses occurring at a healthy BMI. The mechanism underlying return of menses at a healthy weight range may again reflect the complex neurohormonal regulation of menstrual function. Specifically, appropriate fat mass may result in adequate leptin and IGF-1 levels to allow for normal GnRH signaling and resultant menstrual function.17 Our results would be consistent with prior reports that have found that leptin levels were higher in weight-restored patients with eating disorders patients who became eumenorrheic and leptin replacement corrected functional hypothalamic amenorrhea.24,25 Our finding that previously overweight patients resume menses at a younger age and higher BMI z-score reflects both age and weight differences at presentation and menses resumption. Previously overweight patients may develop disordered eating earlier than previously normal weight patients given longer duration of illness but comparable age at presentation. The higher BMI z-score at menses resumption reflects the higher presentation BMI z-score among previously overweight patients, as there was no difference in amount of weight gain between presentation and menses resumption between the two groups. Our results are consistent with earlier findings that previously overweight adolescents resume menses at a significantly higher BMI percentile than their previously normal weight peers without significantly greater weight gain during treatment.7 Given that both groups resumed menses at 14
normal weight status, our findings highlight that weight loss can be achieved in overweight female patients without accompanying pathological consequences, such as disruption of menses. Instead, there may be a threshold weight or rate of weight loss at which these pathological changes occur. Therefore, careful supervision of weight loss and its methods may allow prevention of eating disorder development and its related complications while allowing for beneficial effects of weight loss. Our findings regarding menses resumption must be contextualized in the differences between patients with and without follow up. Barriers to follow up may have included patient perception of disease severity or ability to continue following up at our center, as patients may have been referred from a distant geographic region. The differences in presentation characteristics, such as greater weight suppression with shorter duration of disease, suggests that patients with follow up were sicker at presentation. Thus, our reported weights at menses resumption and associated differences in BMI z-scores reflect disease course in a sicker cohort. We recognize that our study has several limitations. As a single-center study, the generalizability of our findings may be limited by lack of diversity. However, we are a referral site for a large geographic area, and our patients’ demographic and clinical characteristics are consistent with those reported previously.26–29 Like many eating disorder studies, our population is predominantly Caucasian.30 Given the higher rates of overweight/obesity among non-white children, it is important to study weight loss patterns and screen for eating disorder symptomatology in this susceptible population.31 Further, we rely on self-report of multiple variables, including maximum weight and menstrual characteristics, which may reflect inaccurate data. Both healthy adolescents and women with eating disorders underreport weight, suggesting that the group delineations based on self-report underestimate premorbid weight 15
status.32–35 Moreover, the time between resumption of menses and weight measurement may result in an overestimation of the weight needed to resume menses. However, as this did not differ by study group, we do not believe it would bias the relative differences we describe. Additionally, like earlier literature, we did not define a specific time from menarche to establish post-menarchal status, so some of the youngest members of the cohort may have had irregular cycles secondary to normal anovulation that were misidentified as secondary amenorrhea.7 Similarly, in keeping with prior literature, we defined menses resumption as at least one month of menses by self-report, which does not account for recurrent menstrual disturbance.7 Other causes of secondary amenorrhea, such as polycystic ovarian syndrome (PCOS), thyroid disease, pituitary adenoma, and late-onset 21-hydroxylase deficiency were not specifically ruled out in all patients due to limitations on data in the electronic medical record. Given higher prevalence of some of these disorders in overweight patients, this might confound our findings. In conclusion, we found that previously overweight female patients with eating disorders present at greater weights, with greater weight suppression, and longer duration of illness than previously normal weight patients. These findings suggest that symptoms of eating disorders among previously overweight patients are being missed, possibly due to their weight status. Additionally, while there were no differences in rates of amenorrhea at presentation or menses resumption between the groups, the previously overweight patients resumed menses at a weight significantly lower than their premorbid maximum weight as compared to their previously normal weight peers. These results suggest that less weight gain is needed to correct physiological abnormalities in overweight patients as compared to their normal-weight peers, and pre-morbid weight may not be the ideal goal in this subset of patients. Our findings are clinically relevant as they can help guide goals of weight restoration among previously 16
overweight eating disorder patients. They also highlight the importance of close follow up of overweight patients with weight loss to allow early identification of eating disorder in this population and thereby prevent onset of related complications such as amenorrhea and bone disease. Future studies are needed to identify and distinguish thresholds of recovery for overweight patients with eating disorder as compared to their normal-weight counterparts.
Conflict of Interest/Disclaimers: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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32.
Brener ND, Mcmanus T, Galuska DA, Lowry R, Wechsler H. Reliability and validity of self-reported height and weight among high school students. J Adolesc Heal Off Publ Soc Adolesc Med. 2003;32(4):281-287. http://www.ncbi.nlm.nih.gov/pubmed/12667732.
33.
Elgar FJ, Roberts C, Tudor-Smith C, Moore L. Validity of self-reported height and weight and predictors of bias in adolescents. J Adolesc Heal Off Publ Soc Adolesc Med. 2005;37(5):371-375. doi:10.1016/j.jadohealth.2004.07.014
34.
McCabe RE, McFarlane T, Polivy J, Olmsted MP. Eating disorders, dieting, and the accuracy of self-reported weight. Int J Eat Disord. 2001;29(1):59-64. http://www.ncbi.nlm.nih.gov/pubmed/11135334.
35.
Meyer C, Arcelus J, Wright S. Accuracy of self-reported weight and height among women with eating disorders: a replication and extension study. Eur Eat Disord Rev J Eat Disord 22
Assoc. 2009;17(5):366-370. doi:10.1002/erv.950
23
Table 1: Presentation Characteristics
Presentation Characteristic a Age (y) Race (%) White African American Native American Asian Multiracial DSM5 Diagnosis (%) Anorexia Nervosa ARFID
Previously Normal Weight (n=209) 17.9 ± 2.8
Previously Overweight (n=97) 17.8 ± 3.3
297 (94.3) 5 (2.4) 0 3 (1.4) 4 (1.9)
95 (97.9) 0 1 (1.0) 0 1 (1.0)
152 (72.7) 29 (13.9)
52 (53.6) 8 (8.2)
Atypical Anorexia Nervosa Bulimia Nervosa Anorexia Nervosa Type (%) Restricting Binge-eating/Purging Duration of Disease (months)
16 (7.7)
22 (22.7)
12 (5.7)
15 (15.4)
p-value 0.78 0.18
<0.001
0.85 100 (66.2) 51 (33.8) 25.1 ± 28.9
33 (63.5) 19 (36.5) 39.1 ± 43.8
<0.001
Com paris on of pres entat ion char acter istic s betw een prev iousl y nor mal weig ht and
previously overweight patients. a. Continuous variables reported as mean ± standard deviation. Categorical variables are reported as frequency (proportion).
Table 2: Weight Characteristics at Maximum Weight and Presentation
Variable a
Previously Normal Weight (n=209) 48.5 ± 8.11
Previously Overweight (n=97) 54.6 ± 11.57
p-value
18.1 ± 2.5 20.8 ± 23.9
20.6 ± 4.0 43.5 ± 31.3
<0.001 <0.001
-1.33 ± 1.34
-0.29 ± 1.16
<0.001
57.2 ± 7.3 21.3 ± 1.9
72.3 ± 14.2 27.7 ± 5.0
<0.001 <0.001
59.4 ± 18.6
92.3 ± 4.3
<0.001
0.25 ± 0.53
1.53 ± 0.41
<0.001
8.8 ± 5.7
17.7 ± 13.5
<0.001
3.3 ± 2.2
7.1 ± 5.2
<0.001
BMI Percentile Suppression
38.7 ± 22.5
48.7 ± 31.0
0.001
BMI z-score Suppression
1.58 ± 1.19
1.81 ± 1.16
0.206
%Weight loss
15.3 ± 9.4
23.5 ± 13.4
<0.001
Weight at Presentation (kg) BMI at Presentation (kg/m2) BMI Percentile at Presentation BMI z-scores at Presentation Maximum Weight (kg) BMI at Maximum Weight (kg/m2) BMI Percentile at Maximum Weight BMI z-score at Maximum Weight Weight Suppression at Presentation (kg) BMI suppression
<0.001
Comparison of weight and weight-related measurements at reported maximum weight and presentation. a. Continuous variables reported as mean ± standard deviation. Categorical variables are reported as frequency (proportion).
Table 3: Characteristics of Patients Who Resumed Menses Variables a
History of Overweight (n=19) 15.7 ± 2.7
p-value
Age at Presentation (y)
History of Normal Weight (n=40) 17.2 ± 2.5
BMI z-scores at Presentation
-1.59 ± 0.90
-0.65 ± 1.01
0.001
BMI z-scores at Maximum Weight
0.35 ± 0.37
1.59 ± 0.40
<0.001
% Weight loss
19.5 ± 6.1
27.4 ± 11.0
0.001
Age at Resumption of Menses (y)
17.9 ± 2.8
16.1 ± 3.3
0.03
Time from Presentation to Resumption of Menses (months)
8.4 ± 9.1
5.0 ± 8.3
0.17
Weight at Resumption of Menses (kg)
54.8 ± 6.5
54.7 ± 7.0
0.93
BMI at Resumption of Menses (kg/m2) BMI Percentile at Resumption of Menses
20.4 ± 1.9
20.9 ± 2.4
0.37
43.3 ± 20.3
58.4 ± 22.6
0.01
BMI z-score at Resumption of Menses
-0.20 ± 0.61
0.26 ± 0.65
0.009
%Ideal Body Weight at Resumption of Menses
98.2 ± 8.4
105.6 ± 11.7
0.012
Weight Gain Between Presentation and Resumption of Menses (kg)
8.9 ± 5.1
7.2 ± 5.9
0.25
0.04
Weight Loss between Maximum Weight and Weight at Resumption of Menses (kg)
2.3 ± 5.1
11.5 ± 11.1
<0.001
Comparison of presentation and follow up characteristics between previously normal weight and previously overweight patients who resumed menses. a. Continuous variables reported as mean ± standard deviation. Categorical variables are reported as frequency (proportion).
S1083-3188(19)30353-5
DOI:
https://doi.org/10.1016/j.jpag.2019.11.002
Reference:
PEDADO 2417
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 24 June 2019 Revised Date:
2 October 2019
Accepted Date: 4 November 2019
Please cite this article as: Rastogi R, Sieke EH, Nahra A, Sabik J, Rome ES, Return of Menses in Previously Overweight Patients with Eating Disorders, Journal of Pediatric and Adolescent Gynecology (2019), doi: https://doi.org/10.1016/j.jpag.2019.11.002. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc. on behalf of North American Society for Pediatric and Adolescent Gynecology.
Return of Menses in Previously Overweight Patients with Eating Disorders Radhika Rastogi BA1, Erin H. Sieke MD MS2, Alexa Nahra3, Julia Sabik3, Ellen S. Rome MD MPH3
Affiliations: 1Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9501 Euclid Avenue/EC 10, Cleveland, OH 44195, USA 2
The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, 9NW56, Philadelphia,
PA, 19104, USA 3
Department of General Pediatrics and Adolescent Medicine, Cleveland Clinic Children’s
Hospital, 9500 Euclid Ave/R3, Cleveland, OH 44195, USA
Study Institution: Department of General Pediatrics and Adolescent Medicine, Cleveland Clinic Children’s Hospital Funding: None. Disclaimers: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. Corresponding author contact information: Radhika Rastogi Telephone: 914-772-3963 Email Address: [email protected]
1
Abstract: Study objective: Adolescents with eating disorders and a history of overweight present with higher weights, longer duration of disease, but equally severe symptomatology compared to previously normal weight patients. To better delineate treatment goals for this understudied population, we compared weight at menses resumption to premorbid maximum weight among previously overweight and normal weight patients. Design: Retrospective cohort study. Setting: Outpatient adolescent medicine clinic at an eating disorder referral center. Participants: Postmenarchal patients meeting criteria for DSM 5 eating disorders. History of overweight was defined as a BMI ≥ 85th percentile or ≥ 25. Main Outcome Measures: Weight characteristics at presentation and menses resumption (BMI, BMI z-score, change from maximum weight to presentation weight) Results: Previously overweight patients presented with greater mean weight, longer duration of disease and higher BMI than previously normal weight patients. No difference was found in rates of amenorrhea at presentation or menses resumption. Previously overweight patients resumed menses at a younger age and higher BMI z-score. Difference between weight at menses resumption and premorbid maximum weight was greater for previously overweight patients. Conclusions: Previously overweight patients with eating disorders present differently than their normal weight peers, so reliance on weight status as a screening criteria may result in underdiagnosis. Though BMI z-scores associated with menses resumption are higher for 2
previously overweight patients, there is no difference in weight gain between presentation and menses resumption and time to menses resumption compared to previously normal weight patients. Moreover, menses resumption occurred at weights significantly lower than premorbid maximum weight for previously overweight patients, so restoration to highest premorbid weight is not necessary. Keywords: Eating disorders, Eating and Feeding disorders, Anorexia Nervosa, Menstruation Disturbance
3
Introduction The rising prevalence of adolescent overweight and obesity has resulted in an emphasis on weight loss by clinicians and health education curricula. Likely reflecting this messaging, overweight adolescents report greater body dissatisfaction and concern about weight than normal weight adolescents.1 These risk factors result in a higher likelihood of eating disorder thoughts and behaviors such as bingeing, purging, diet pill and laxative use among these patients.1–4 The reported prevalence of a history of overweight or obesity among pediatric patients with eating disorders ranges from 11-36%.5–7 Previously overweight adolescents with eating disorders present differently than their previously normal-weight peers. Specifically, they present with greater weight suppression (difference between premorbid highest weight and presentation weight), longer duration of disease, higher body mass index (BMI).6,8 However, despite no difference in symptomatology, including comparable rates of amenorrhea and with similar scores on psychological measures, previously overweight adolescents with eating disorders are less likely to be hospitalized.6,8 Patients with eating disorders, including anorexia nervosa, atypical anorexia nervosa, avoidant/restrictive food intake disorder, and bulimia nervosa, can present with both primary and secondary amenorrhea.9 Amenorrhea is associated with comorbidities such as lower peak bone mass and impaired neuropsychological functioning; resumption of menses is a well-established marker of physiologic recovery among patients with eating disorders.10,11 In a previous study, previously overweight adolescents with secondary amenorrhea resumed menses at a significantly higher weight than their previously normal weight peers, suggesting that goal recovery weights may differ based on premorbid overweight status.7
4
There remains a paucity of longitudinal data on cohorts of previously overweight patients. Given that previous weight status may impact treatment goal weights, comparison between premorbid maximum weight and weight at menses resumption is necessary. Further, there is lack of literature on incidence of history of overweight as well as amenorrhea and subsequent return of menses in patients with bulimia nervosa and avoidant/restrictive food intake disorder (ARFID), since prior studies have focused their investigation exclusively on patients with anorexia nervosa and atypical anorexia nervosa. To address these gaps in knowledge, we aimed to investigate the differences in presenting characteristics, including 1. eating disorder diagnosis, 2. weight status, 3. weight suppression, and 4. duration of disease between patients with eating disorders with and without a history of overweight. We also compared menstrual characteristics, including 1. rates of secondary amenorrhea and 2. weight status at menses resumption between the groups. In keeping with the prior literature, we hypothesized that previously overweight patients would present at higher weights but with greater weight suppression and longer duration of illness with no differences in rates of amenorrhea. We further hypothesized that previously overweight patients would resume menses at higher weights than previously normal weight patients.
5
Methods Study population A retrospective longitudinal cohort study was conducted on female patients hospitalized and followed in outpatient clinic for nutritional insufficiency at the Cleveland Clinic, an academic medical center, between January 2008 and January 2017 (n=420). Data were collected from the electronic medical record for up to 5 years or until the last documented clinic visit from the time of hospitalization. Inclusion criteria included female sex, presentation for evaluation of nutritional insufficiency and care by an adolescent medicine physician, so patients with a wide age range were included. Exclusion criteria included premenarchal status at presentation, nutritional insufficiency secondary to a non-eating disorder diagnosis, and missing data on presentation characteristics. Patients on hormonal contraception at presentation or follow up were excluded from analysis on menstrual characteristics, but included in the analysis on presentation characteristics. The study protocol was approved by the Cleveland Clinic Institutional Review Board. Eating disorder diagnoses of anorexia nervosa, bulimia nervosa, other specified feeding or eating disorder (specifically atypical anorexia), and ARFID were assigned by adolescent medicine specialists based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM 5) criteria. For patients seen before 2013, diagnoses were retrospectively assigned based on the DSM 5 criteria by an adolescent medicine physician knowledgeable about the patient’s history. BMI at maximum weight was calculated based on self-reported maximum weight, height at maximum weight, and age at maximum weight prior to presentation, as previously described in other published studies.7,8 History of overweight was defined as a BMI 6
≥85th percentile for those younger than 20 years, and a BMI ≥ 25 for those 20 years or older at maximum weight. History of normal weight was defined as BMI between 5th and 85th percentile at age <20 years and BMI between 18.5 and 25 at age ≥ 20 years at maximum weight. Secondary amenorrhea was defined as absence of menses for at least 3 months among postmenarchal patients.12 Return of menses was based on self-report of at least 1 month of menses at follow up visits for all patients.7 Weight and height at resumption of menses were collected from the closest office or inpatient visit following reported date of return of menses. Measures Age, race/ethnicity, duration of illness, anthropometric measures (height, weight), menstrual status, and hormonal contraceptive use were collected at presentation and follow-up visits. Patients were weighed on a scale in a hospital gown after voiding. Patients were blinded to their weights. Heights were obtained on a standard stadiometer. Heights and weights are obtained by the same eating disorder nursing team. Weight of menses resumption was taken from the closest office visit subsequent to the reported date of resumption which varied from days to months. BMI percentiles and z-scores were calculated for patients younger than 20 years based on the Centers for Disease Control and Prevention growth charts.13 Weight suppression was calculated as the difference between maximum weight and presentation weight, both in absolute numbers (kilograms) and in percent of maximum weight. Similarly, BMI suppression, BMI percentile suppression, and BMI z-score suppression were calculated as the difference between the measures at maximum weight and presentation. Statistical Analysis
7
The primary outcome of interest was the difference in weight status among previously overweight and previously normal weight patients at time of presentation and at return of menses. Menses resumption analysis was limited to patients who were amenorrheic at presentation and had follow up menstrual data available. All variables were assessed for normality of distribution. Bivariate analyses were used to compare presentation and follow up data. Independent t tests were used to compare continuous variables and chi square analyses were used to compare categorical variables. Data are described as means with standard deviations for continuous variables and counts and counts with percentages for categorical variables. Significance was established a priori at an α level of 0.05. Statistical analyses were conducted on STATA version 14 (Stata Inc., Plano TX).
8
Results Presentation Characteristics Of the 420 female patients who presented for evaluation of nutritional insufficiency between 2008-2017, 114 did not qualify: 5 had diagnoses other than an eating disorder, 41 were premenarchal, 7 were underweight at their maximum weight, and 61 had missing presentation data. A total of 306 patients were included in the study. Of these, 31% of patients had a history of overweight. Patient demographics and diagnoses are presented in Table 1. A greater proportion of the previously overweight patients were diagnosed with atypical anorexia or bulimia nervosa whereas more previously normal weight patients were diagnosed with anorexia nervosa or ARFID. Mean duration of disease prior to presentation was longer in the previously overweight group. Weight characteristics at maximum weight and presentation are compared in Table 2. BMI at presentation was higher among the previously overweight group. Weight suppression, both in absolute amount and relative to maximum weight, was greater in previously overweight patients. Weight characteristics also differed by DSM 5 diagnosis. Mean maximum BMI was higher among patients with atypical anorexia or bulimia nervosa (26.4 kg/m2 ± 5.5 and 26.4 kg/m2 ± 4.4) as compared to patients with anorexia nervosa or ARFID (22.7 kg/m2 ± 3.9 and 21.6 kg/m2 ± 3.2) (p<0.001). Maximum weights differed similarly, with patients with atypical anorexia or bulimia nervosa having a higher maximum weight (69.9kg ±14.2 and 71.5kg ± 12.5) than patients with anorexia nervosa or ARFID (60.4kg ± 11.1 and 56kg ± 7.8) (p<0.001). At 9
presentation, patients with anorexia nervosa and ARFID presented with lower BMIs (17.8 kg/m2 ± 2.1 and 17.53 kg/m2 ± 2.7) than patients with atypical anorexia or bulimia nervosa (22.5 kg/m2 ± 3.6 and 23.6 kg/m2 ± 3.2) (p<0.001). Presentation weights followed a similar pattern, with patients with anorexia nervosa or ARFID weighing less at presentation (47.6kg ± 6.4 and 46.0kg ± 7.8) than patients with atypical anorexia or bulimia nervosa (60.2kg ± 10.9 and 64kg ± 11.1) (p<0.001). Lastly, weight suppression was greatest among patients with anorexia nervosa (12.8kg ± 10.1), comparable among those with ARFID and atypical anorexia (9.9kg ± 6.8 and 9.7kg ± 9.7), and lowest among patients with bulimia nervosa (7.5kg ± 10) (p=0.016). Menstrual Characteristics Rates of amenorrhea at presentation were comparable between previously normal and previously overweight patients (75 (35.9%) vs. 43 (44%), p=0.34). Four patients were excluded from menses resumption analysis as they were on hormonal contraception at follow up. Menstrual characteristics at follow up are presented in Table 3. Though less than ⅓ of patients had follow up, rates of follow up did not differ between patients with and without a history of overweight (28.2% vs. 27.8%, p = 1.0). Rates of follow up differed by diagnosis with 67 (33%) patients with anorexia nervosa, 8 (21%) patients with atypical anorexia nervosa, 10 (27%) patients with ARFID, and 1 (4%) patient with bulimia nervosa having follow up data (p=0.01). Of the 59 previously normal weight patients who had follow up data, 40 (67.7%) resumed menses, 18 (30.5%) continued to be amenorrheic, and 1 (1.7%) was on hormonal contraception. Of the 27 previously overweight patients with follow up data, 19 (70.3%) resumed menses, 5 (18.5%) continued to be amenorrheic, and 3 (11.1%) were on hormonal contraception. There were no differences in menstrual status at follow up between patients with and without a history 10
of overweight (p=0.09). Time between menses resumption and weight measurement did not differ by study group (5.5 ±7.3 months vs. 4.1 ± 5.1, p=0.44). Previously overweight patients resumed menses at a younger age and higher BMI z-score than their normal-weight peers. There was no difference in time between presentation and resumption of menses between the groups (p=0.17). Previously normal weight patients resumed menses closer to their maximum weight than previously overweight patients did. Other characteristics, including rates of amenorrhea at presentation, duration of amenorrhea, menstrual status at follow up, and weight gain from presentation to menses resumption did not differ by study group. Menstrual status did not differ by DSM 5 diagnosis Though rates of follow up did not differ by study group, since less than 1/3 of patients were included in follow up analysis, we compared patients with and without follow up to identify sources of bias. Compared to patients without follow up, patients with follow up reported maximum weight at a younger age (15.1 ± 2.5 years vs. 15.9 ± 2.7 years, p=0.01). Maximum weight, BMI, BMI percentiles, and BMI z-scores at maximum weight did not differ. Patients with follow up presented at a younger age (17.2 ±2.9 years vs. 18.1 ± 3.0, p=0.010), lower weight (46.7 ± 8.1 kg vs. 51.8 ± 10.0 kg, p<0.001), BMI (17.5 ± 3 vs. 19.3 ± 3.3, p=0.007), BMI percentile (15.8 ± 20.7 vs. 32.1 ± 29.8, p<0.001), and BMI z-score (-1.58 ± 1.34 vs. -0.87 ± 1.45, p<0.001). Follow up patients had fewer months of disease (18.0 ± 19.4 vs. 34.3 ± 38.8, p<0.001) with greater weight suppression (13.5 ± 7.5 kg vs. 10.9 ± 10.5 kg, p=0.033). Patients with follow up were more likely to have anorexia nervosa (77.9% vs. 62.3%) and less likely to have atypical anorexia nervosa (9.3% vs. 13.6%), ARFID (11.6% vs. 12.3%), and bulimia nervosa (1.2% vs. 11.8%) (p=0.011).
11
Discussion We found that 31% of the patients presenting for treatment of eating disorders had a history of overweight. They presented at higher weight status, but with greater weight suppression, and longer duration of disease than their previously normal weight peers. They were more likely to be diagnosed with atypical anorexia or bulimia nervosa than their previously normal weight peers. Although the rates of amenorrhea at presentation and menses resumption did not differ by group, previously overweight patients resumed menses at a younger age and a higher BMI z-score than their previously normal weight peers. Further, previously normal weight patients resumed menses at a weight significantly closer to their maximum weight than did previously overweight patients. Our findings of differences in the initial presentation between the two study groups are consistent with and validate previously reported presentation characteristics of this patient population.6 Our findings of greater disease duration and weight suppression among patients with premorbid overweight provides additional evidence of bias against timely identification of eating disorder symptoms in these patients. Therefore, our findings and those of prior studies likely underestimate the true burden of eating disorders among overweight or previously overweight adolescents as many of them do not achieve underweight status despite significant weight loss and thus may not be screened for eating disorders.6,8 In keeping with previous findings, we also report no differences between rates of amenorrhea at presentation and menses resumption between the two groups.6 Interestingly, our previously overweight patients presented with significantly greater weight suppression, which has been associated with worse symptomatology, such as higher rates of amenorrhea, regardless 12
of BMI.14 The mechanisms behind amenorrhea secondary to nutritional insufficiency are complex and involve degree of weight suppression, body fat mass, and levels of hormones including gonadotropins and leptin.15,16 Weight loss disrupts the hypothalamic-pituitary-ovarian (HPO) axis by altering the pulsatility of gonadotropin releasing hormone (GnRH), which maintains normal menstrual function by modulating estrogen levels.17 This relationship is mediated by neurotrophic hormones such as leptin and IGF-1, which regulate the function of GnRH releasing neurons.18,19 Both leptin and IGF-1 levels correlate with fat mass.17,20,21 Weight loss with relative sparing of fat mass in malnourished young women with disordered eating has been associated with preservation of regular menstrual function.21 Thus, in our previously overweight population, comparably higher fat mass at presentation may protect against the degree of menstrual disturbance that would have been expected given their degree of weight suppression compared to their normal weight peers. Our results significantly further prior literature by comparing maximum weight to weight at return of menses in a longitudinal cohort. This comparison is clinically relevant given the lack of guidelines addressing goals of weight restoration during treatment among previously overweight patients.22 Without guidelines, there is variation in approaches to weight restoration, as some clinicians rely on population-based “ideal body weight”, derived from sources such as the Metropolitan Life Insurance Company, whereas others seek to restore premorbid weight.23 An earlier study recommended treatment weight goals should target the 14th-39th BMI percentile.22 However, unlike our previously overweight patients who presented with normal or overweight status, this study’s population was underweight at presentation and there was no evaluation of pre-morbid weight status.22 In comparison, we found that menses resumed at higher BMI percentiles and %ideal body weight than those reported before, independent of 13
premorbid weight status.11 This difference may reflect differences in age at presentation and menses resumption, as our population was older with more years postmenarche. That previously normal weight patients in our cohort resumed menses at an average of 2kg below their maximum weight whereas previously overweight patients resumed menses at an average of 11kg below their maximum weight suggests that restoration to premorbid maximum weight is not necessary for physiologic restoration. Indeed, regardless of premorbid weight status, we found evidence of physiologic recovery through return of menses occurring at a healthy BMI. The mechanism underlying return of menses at a healthy weight range may again reflect the complex neurohormonal regulation of menstrual function. Specifically, appropriate fat mass may result in adequate leptin and IGF-1 levels to allow for normal GnRH signaling and resultant menstrual function.17 Our results would be consistent with prior reports that have found that leptin levels were higher in weight-restored patients with eating disorders patients who became eumenorrheic and leptin replacement corrected functional hypothalamic amenorrhea.24,25 Our finding that previously overweight patients resume menses at a younger age and higher BMI z-score reflects both age and weight differences at presentation and menses resumption. Previously overweight patients may develop disordered eating earlier than previously normal weight patients given longer duration of illness but comparable age at presentation. The higher BMI z-score at menses resumption reflects the higher presentation BMI z-score among previously overweight patients, as there was no difference in amount of weight gain between presentation and menses resumption between the two groups. Our results are consistent with earlier findings that previously overweight adolescents resume menses at a significantly higher BMI percentile than their previously normal weight peers without significantly greater weight gain during treatment.7 Given that both groups resumed menses at 14
normal weight status, our findings highlight that weight loss can be achieved in overweight female patients without accompanying pathological consequences, such as disruption of menses. Instead, there may be a threshold weight or rate of weight loss at which these pathological changes occur. Therefore, careful supervision of weight loss and its methods may allow prevention of eating disorder development and its related complications while allowing for beneficial effects of weight loss. Our findings regarding menses resumption must be contextualized in the differences between patients with and without follow up. Barriers to follow up may have included patient perception of disease severity or ability to continue following up at our center, as patients may have been referred from a distant geographic region. The differences in presentation characteristics, such as greater weight suppression with shorter duration of disease, suggests that patients with follow up were sicker at presentation. Thus, our reported weights at menses resumption and associated differences in BMI z-scores reflect disease course in a sicker cohort. We recognize that our study has several limitations. As a single-center study, the generalizability of our findings may be limited by lack of diversity. However, we are a referral site for a large geographic area, and our patients’ demographic and clinical characteristics are consistent with those reported previously.26–29 Like many eating disorder studies, our population is predominantly Caucasian.30 Given the higher rates of overweight/obesity among non-white children, it is important to study weight loss patterns and screen for eating disorder symptomatology in this susceptible population.31 Further, we rely on self-report of multiple variables, including maximum weight and menstrual characteristics, which may reflect inaccurate data. Both healthy adolescents and women with eating disorders underreport weight, suggesting that the group delineations based on self-report underestimate premorbid weight 15
status.32–35 Moreover, the time between resumption of menses and weight measurement may result in an overestimation of the weight needed to resume menses. However, as this did not differ by study group, we do not believe it would bias the relative differences we describe. Additionally, like earlier literature, we did not define a specific time from menarche to establish post-menarchal status, so some of the youngest members of the cohort may have had irregular cycles secondary to normal anovulation that were misidentified as secondary amenorrhea.7 Similarly, in keeping with prior literature, we defined menses resumption as at least one month of menses by self-report, which does not account for recurrent menstrual disturbance.7 Other causes of secondary amenorrhea, such as polycystic ovarian syndrome (PCOS), thyroid disease, pituitary adenoma, and late-onset 21-hydroxylase deficiency were not specifically ruled out in all patients due to limitations on data in the electronic medical record. Given higher prevalence of some of these disorders in overweight patients, this might confound our findings. In conclusion, we found that previously overweight female patients with eating disorders present at greater weights, with greater weight suppression, and longer duration of illness than previously normal weight patients. These findings suggest that symptoms of eating disorders among previously overweight patients are being missed, possibly due to their weight status. Additionally, while there were no differences in rates of amenorrhea at presentation or menses resumption between the groups, the previously overweight patients resumed menses at a weight significantly lower than their premorbid maximum weight as compared to their previously normal weight peers. These results suggest that less weight gain is needed to correct physiological abnormalities in overweight patients as compared to their normal-weight peers, and pre-morbid weight may not be the ideal goal in this subset of patients. Our findings are clinically relevant as they can help guide goals of weight restoration among previously 16
overweight eating disorder patients. They also highlight the importance of close follow up of overweight patients with weight loss to allow early identification of eating disorder in this population and thereby prevent onset of related complications such as amenorrhea and bone disease. Future studies are needed to identify and distinguish thresholds of recovery for overweight patients with eating disorder as compared to their normal-weight counterparts.
Conflict of Interest/Disclaimers: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
17
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23
Table 1: Presentation Characteristics
Presentation Characteristic a Age (y) Race (%) White African American Native American Asian Multiracial DSM5 Diagnosis (%) Anorexia Nervosa ARFID
Previously Normal Weight (n=209) 17.9 ± 2.8
Previously Overweight (n=97) 17.8 ± 3.3
297 (94.3) 5 (2.4) 0 3 (1.4) 4 (1.9)
95 (97.9) 0 1 (1.0) 0 1 (1.0)
152 (72.7) 29 (13.9)
52 (53.6) 8 (8.2)
Atypical Anorexia Nervosa Bulimia Nervosa Anorexia Nervosa Type (%) Restricting Binge-eating/Purging Duration of Disease (months)
16 (7.7)
22 (22.7)
12 (5.7)
15 (15.4)
p-value 0.78 0.18
<0.001
0.85 100 (66.2) 51 (33.8) 25.1 ± 28.9
33 (63.5) 19 (36.5) 39.1 ± 43.8
<0.001
Com paris on of pres entat ion char acter istic s betw een prev iousl y nor mal weig ht and
previously overweight patients. a. Continuous variables reported as mean ± standard deviation. Categorical variables are reported as frequency (proportion).
Table 2: Weight Characteristics at Maximum Weight and Presentation
Variable a
Previously Normal Weight (n=209) 48.5 ± 8.11
Previously Overweight (n=97) 54.6 ± 11.57
p-value
18.1 ± 2.5 20.8 ± 23.9
20.6 ± 4.0 43.5 ± 31.3
<0.001 <0.001
-1.33 ± 1.34
-0.29 ± 1.16
<0.001
57.2 ± 7.3 21.3 ± 1.9
72.3 ± 14.2 27.7 ± 5.0
<0.001 <0.001
59.4 ± 18.6
92.3 ± 4.3
<0.001
0.25 ± 0.53
1.53 ± 0.41
<0.001
8.8 ± 5.7
17.7 ± 13.5
<0.001
3.3 ± 2.2
7.1 ± 5.2
<0.001
BMI Percentile Suppression
38.7 ± 22.5
48.7 ± 31.0
0.001
BMI z-score Suppression
1.58 ± 1.19
1.81 ± 1.16
0.206
%Weight loss
15.3 ± 9.4
23.5 ± 13.4
<0.001
Weight at Presentation (kg) BMI at Presentation (kg/m2) BMI Percentile at Presentation BMI z-scores at Presentation Maximum Weight (kg) BMI at Maximum Weight (kg/m2) BMI Percentile at Maximum Weight BMI z-score at Maximum Weight Weight Suppression at Presentation (kg) BMI suppression
<0.001
Comparison of weight and weight-related measurements at reported maximum weight and presentation. a. Continuous variables reported as mean ± standard deviation. Categorical variables are reported as frequency (proportion).
Table 3: Characteristics of Patients Who Resumed Menses Variables a
History of Overweight (n=19) 15.7 ± 2.7
p-value
Age at Presentation (y)
History of Normal Weight (n=40) 17.2 ± 2.5
BMI z-scores at Presentation
-1.59 ± 0.90
-0.65 ± 1.01
0.001
BMI z-scores at Maximum Weight
0.35 ± 0.37
1.59 ± 0.40
<0.001
% Weight loss
19.5 ± 6.1
27.4 ± 11.0
0.001
Age at Resumption of Menses (y)
17.9 ± 2.8
16.1 ± 3.3
0.03
Time from Presentation to Resumption of Menses (months)
8.4 ± 9.1
5.0 ± 8.3
0.17
Weight at Resumption of Menses (kg)
54.8 ± 6.5
54.7 ± 7.0
0.93
BMI at Resumption of Menses (kg/m2) BMI Percentile at Resumption of Menses
20.4 ± 1.9
20.9 ± 2.4
0.37
43.3 ± 20.3
58.4 ± 22.6
0.01
BMI z-score at Resumption of Menses
-0.20 ± 0.61
0.26 ± 0.65
0.009
%Ideal Body Weight at Resumption of Menses
98.2 ± 8.4
105.6 ± 11.7
0.012
Weight Gain Between Presentation and Resumption of Menses (kg)
8.9 ± 5.1
7.2 ± 5.9
0.25
0.04
Weight Loss between Maximum Weight and Weight at Resumption of Menses (kg)
2.3 ± 5.1
11.5 ± 11.1
<0.001
Comparison of presentation and follow up characteristics between previously normal weight and previously overweight patients who resumed menses. a. Continuous variables reported as mean ± standard deviation. Categorical variables are reported as frequency (proportion).