Menstrual dysfunction in anorexia nervosa

doi:10.1016/j.jpag.2004.01.003

Journal of Pediatric and Adolescent Gynecology

Volume 17, Issue 2, April 2004, Pages 81-85

https://doi.org/10.1016/j.jpag.2004.01.003 Get rights and content

Abstract

Amenorrhea is a hallmark sign of anorexia nervosa. Its cause is multifactorial and its resolution necessitates treatment of the underlying eating disorder. The neuroendocrine changes associated with menstrual abnormalities in underweight and weight recovered anorexia nervosa, recent research on osteopenia, and treatment recommendations are addressed.

Introduction

Anorexia nervosa affects 1% to 3% of adolescents and young adults in the United States.1., 2. Menstrual irregularities are often the presenting concern, placing the gynecologic clinician in an advantageous position for accurate and timely diagnosis of the eating disorder. This article will review the pathophysiology of menstrual problems in patients with anorexia nervosa and update the reader on current treatment recommendations for associated osteopenia.

Section snippets

Diagnosis

Amenorrhea is one of the four diagnostic criteria of anorexia nervosa (see Table 1).³ In up to two thirds of patients, absence of menses precedes significant weight loss,4., 5. making initial diagnosis of the eating disorder more difficult. Evaluation of amenorrhea in all patients must include thorough examination of exercise and nutritional habits. Body image should also be explored. The SCOFF questionnaire (see Table 2) is an easily administered screening tool for use in primary care settings

Physical examination

Physical examination of a patient with anorexia nervosa generally reveals bradycardia, hypothermia, dry skin, lanugo, and yellowing of the skin due to hypercarotenemia. Severe emaciation, as noted by the scaphoid abdomen and loss of subcutaneous fat in the extremities and trunk, may be overlooked if the patient is not examined in a gown. Submandibular adenopathy or parotid gland enlargement result from frequent emesis. A cardiac murmur may signify anemia or mitral valve prolapse, a reversible

Laboratory evaluation

Laboratory evaluation in the patient with anorexia identifies medical complications of malnutrition and should include a complete blood cell count, electrolytes, blood urea nitrogen, creatinine, and liver function tests. Luteinizing hormone (LH), follicle stimulating hormone (FSH), and serum estradiol levels are all low in women with anorexia nervosa. Prolactin and thyroid stimulating hormone (TSH) are normal (Table 3).4., 10. Assessment of the hypothalamic-pituitary-ovarian (HPO) axis need

Exercise and the female athlete triad

Menstrual irregularities associated with excessive exercise in non eating-disordered athletes are due to hypothalamic dysfunction with a decrease in the pulse frequency of gonadotropin-releasing hormone (GnRH), leading to low levels of FSH, LH, and estradiol.¹⁹ Repeated administration of exogenous GnRH results in normalization of LH secretion patterns in anorectics, but demonstrates an exaggerated response in non eating-disordered athletes suggesting a different mechanism for athletic

Menstrual irregularities in weight recovered anorexia

The return of menses is directly correlated with restoration of an individualized healthy body weight. No relationship has been found between return of menses and percent body fat or BMI.21., 22. Over 85% of patients will have spontaneous return to menses within 6 months of achieving a weight 90% of their ideal body weight.²²

Persistent amenorrhea may reflect improper terminology in that these patients are not truly “weight recovered” but merely of weight in normative ranges. Amenorrheic

Bone mineral density

The decreased bone formation and increased resorption seen in anorexia nervosa are associated with high rates of osteopenia and osteoporosis.³³ Osteopenia, or reduced bone mass, has been shown in 44% to 92% of patients presenting with amenorrhea less than 24 months duration.34., 35., 36. Risk of osteoporosis, consisting of decreased bone mass, decreased bone strength, and pathologic fracture, correlates best with duration of illness and the patient's body mass index.37., 38., 39., 40., 41. Bone

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Eating Disorders (ED) are characterized by low remission rates, treatment drop-out, and residual symptoms. To improve assessment and treatment of ED, the staging approach has been proposed. This systematic scoping review is aimed at mapping the existing staging models that explicitly propose stages of the progression of ED.
A systematic search of PubMed, PsycINFO, Scopus was conducted with the terms staging, anorexia nervosa, bulimia nervosa, binge-eating disorders, eating disorders. Eleven studies met inclusion criteria presenting nine ED staging models, mostly for anorexia nervosa. Three were empirically tested, one of which was through an objective measure specifically developed to differentiate between stages. Most staging models featured early stages in which the exacerbation of EDs unfolds and acute phases are followed by chronic stages. Intermediate stages were not limited to acute stages, but also residual phases, remission, relapse, and recovery. The criteria for stage differentiation encompassed behavioral, psychological, cognitive, and physical features including body mass index and illness duration. One study recommended stage-oriented interventions. The current review underscores the need to empirically test the available staging models and to develop and test new proposals of staging models for other ED populations. The inclusion of criteria based on medical features and biomarkers is recommended. Staging models can potentially guide assessment and interventions in daily clinical settings.
Etiology and management of amenorrhea in adolescent and young adult women
2022, Current Problems in Pediatric and Adolescent Health Care
In this article, we will review the etiology and management of amenorrhea in adolescent and young adult women, beginning with the diagnostic work-up and followed by etiologies organized by system. Most cases of amenorrhea are caused by dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis, which is the major regulator of the female reproductive hormones: estrogen and progesterone. We begin by reviewing hypothalamic etiologies, including eating disorders and relative energy deficiency in sport. Then, pituitary causes of amenorrhea are reviewed, including hyperprolactinemia, empty sella syndrome, Sheehan's syndrome and Cushing's syndrome. Next, ovarian causes of amenorrhea are reviewed, including polycystic ovarian syndrome and primary ovarian insufficiency. Finally, other etiologies of amenorrhea are discussed, including thyroid disease, adrenal disease and reproductive tract anomalies. In conclusion, there is a wide and diverse range of causes of amenorrhea in adolescents that originate from any level of the HPO axis, as well as anatomic and chromosomal etiologies. Treatment should be focused on the underlying cause. Preservation of bone density and risk of fractures should be discussed with amenorrheic patients since many causes of amenorrhea can result in decreased bone density and may be irreversible.
Pubertal mammary gland development is a key determinant of adult mammographic density
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Mammographic density refers to the radiological appearance of fibroglandular and adipose tissue on a mammogram of the breast. Women with relatively high mammographic density for their age and body mass index are at significantly higher risk for breast cancer. The association between mammographic density and breast cancer risk is well-established, however the molecular and cellular events that lead to the development of high mammographic density are yet to be elucidated. Puberty is a critical time for breast development, where endocrine and paracrine signalling drive development of the mammary gland epithelium, stroma, and adipose tissue. As the relative abundance of these cell types determines the radiological appearance of the adult breast, puberty should be considered as a key developmental stage in the establishment of mammographic density. Epidemiological studies have pointed to the significance of pubertal adipose tissue deposition, as well as timing of menarche and thelarche, on adult mammographic density and breast cancer risk. Activation of hypothalamic-pituitary axes during puberty combined with genetic and epigenetic molecular determinants, together with stromal fibroblasts, extracellular matrix, and immune signalling factors in the mammary gland, act in concert to drive breast development and the relative abundance of different cell types in the adult breast. Here, we discuss the key cellular and molecular mechanisms through which pubertal mammary gland development may affect adult mammographic density and cancer risk.
Return of Menses in Previously Overweight Patients with Eating Disorders
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Citation Excerpt :
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 of BMI.14 The mechanisms behind amenorrhea secondary to nutritional insufficiency are complex and involve a degree of weight suppression, body fat mass, and levels of hormones including gonadotropins and leptin.15,16 Weight loss disrupts the hypothalamic-pituitary-ovarian axis by altering the pulsatility of gonadotropin releasing hormone (GnRH), which maintains normal menstrual function by modulating estrogen levels.17
Adolescents with eating disorders and a history of overweight present with higher weights, longer duration of disease, but equally severe symptomatology compared with previously normal weight patients. To better delineate treatment goals for this understudied population, we compared weight at menses resumption with premorbid maximum weight among previously overweight and normal weight patients.
Retrospective cohort study.
Outpatient adolescent medicine clinic at an eating disorder referral center.
Postmenarchal patients meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition eating disorders. History of overweight was defined as a body mass index (BMI) greater than or equal to the 85th percentile or 25 or more.
Weight characteristics at presentation and menses resumption (BMI, BMI z-score, change from maximum weight to presentation weight)
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-scores. The difference between weight at menses resumption and premorbid maximum weight was greater for previously overweight patients.
Previously overweight patients with eating disorders present differently than their normal-weight peers, so reliance on weight status as a screening criterion might result in underdiagnosis. Although BMI z-scores associated with menses resumption are higher for previously overweight patients, there is no difference in weight gain between presentation and menses resumption and time to menses resumption compared with 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.
Medical Complications of Eating Disorders in Youth
2019, Child and Adolescent Psychiatric Clinics of North America
Citation Excerpt :
ED adolescents also risk reduced bone mineral density primarily due to poor nutritional intake, low BMI, and reduced fat mass.55,56,58,64,83–87 Leptin plays a key role in energy homeostasis, and levels are low in malnourished states.55,60,88–92 Recent studies demonstrate that if leptin levels are normalized, menstrual function and thyroid and bone markers improve in hypothalamic amenorrhea.93–96
Physiologic and Pathophysiologic Alterations of the Neuroendocrine Components of the Reproductive Axis
2019, Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management: Eighth Edition
The neurohormonal control of reproduction involves a network of central and peripheral signals in the hypothalamic-pituitary-gonadal axis. The gonadotropin-releasing hormone (GnRH) system plays a crucial part in this axis.
Integration of multiple signals ultimately results in neuronal release of GnRH, which then travels via the hypothalamic–hypophyseal portal circulation to the anterior pituitary gland, where it binds to the GnRH receptor 1 and upregulates synthesis and secretion of two pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH secretion is pulsatile with discrete bursts of GnRH affecting the release of pulses of LH and FSH by the pituitary. This chapter describes medical conditions as well as endogenous and exogenous factors that result in abnormalities of this complex hypothalamic-pituitary axis.

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^☆: Synopsis: A review of recent research in anorexia nervosa regarding osteopenia and neuroendocrine changes associated with menstrual abnormalities in underweight and weight recovery, with diagnosis and management options is provided.

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Mini-ReviewMenstrual dysfunction in anorexia nervosa☆

Abstract

Introduction

Section snippets

Diagnosis

Physical examination

Laboratory evaluation

Exercise and the female athlete triad

Menstrual irregularities in weight recovered anorexia

Bone mineral density

Fertil Steril

Eur J Obstet Gynecol Reprod Biol

Psychiatry Res

Endocrinol Metab Clin North Am

J Am Acad Child Adolesc Psychiatry

J Pediatr Adolesc Gynecol

J Pediatr Adolesc Gynecol

J Adolesc Health

Practice guideline for the treatment of patients with eating disorders (revision)

Am J Psychiatry

Secular trends in the incidence of anorexia nervosa: Integrative review of population-based studies

Int J Eat Disord

Diagnostic and Statistical Manual of Mental Disorders

Hypothalamic-endocrine dysfunction in anorexia nervosa

Mayo Clin Proc

Anorexia nervosa: Demographic and clinical features in 94 cases

Psychosom Med

The SCOFF questionnaire: Assessment of a new screening tool for eating disorders

BMJ

Four simple questions can help screen for eating disorders

J Gen Intern Med

Mitral valve prolapse in patients with anorexia nervosa and bulimia

Arch Intern Med

Mitral valve prolapse in anorexia nervosa

Ann Intern Med

Amenorrhoea, body weight and serum hormone concentrations, with particular reference to prolactin and thyroid hormones in anorexia nervosa

Psychol Med

LHRH responsiveness in anorexia nervosa: Intactness despite prepubertal circadian LH pattern

Psychosom Med

Anorexia nervosa. Immaturity of the 24-hour luteinizing hormone secretory pattern

N Engl J Med

The effects of clomiphene citrate on the hypothalamic-pituitary-gonadal axis in anorexia nervosa

Psychol Med

Assessment of the negative and positive feedback effects of administered oestrogen on gonadotrophin release in patients with anorexia nervosa

Psychol Med

Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: A randomized trial

J Clin Endocrinol Metab

Abnormal hypothalamic pituitary adrenal function in anorexia nervosa

N Engl J Med

Mini-Review
Menstrual dysfunction in anorexia nervosa☆