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Endocrine Society issues clinical practice guideline on functional hypothalamic amenorrhea
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Women with functional hypothalamic amenorrhea should receive multidisciplinary treatment, including medical, dietary and mental health support, to avoid potential chronic health complications ranging from infertility to osteoporosis, according to a new clinical practice guideline released by the Endocrine Society.
Functional hypothalamic amenorrhea, a form of chronic anovulation not due to identifiable organic causes, is often associated with stress, weight loss, excessive exercise or a combination of these factors. The condition occurs when the hypothalamus slows or stops releasing gonadotropin-releasing hormone, and often affects adolescent girls or women with low body weight, a low percentage of body fat, a very low calorie or fat intake, and emotional stress. The most significant, acute risks for functional hypothalamic amenorrhea include delayed puberty, amenorrhea, infertility and the long-term health consequences of hypoestrogenism, including decreased bone density.
“There is a misconception that functional hypothalamic amenorrhea is seen only in the underweight patient, which is not true,” Catherine M. Gordon, MD, MSc, director of the division of adolescent/transition medicine at Cincinnati Children’s Hospital Medical Center, told Endocrine Today. “Our guidelines review how the seemingly ‘healthy’ teen can present with functional hypothalamic amenorrhea, or the normal-weight, but stressed, adult with infertility. We also underscore the importance of bone density screening after 6 months of amenorrhea, as bone is one of the tissues most detrimentally affected in these patients.
“On the treatment front, we underscore the importance of psychological support for both adolescents and adults and select cases where short-term transdermal estrogen therapy may be helpful if a reasonable trial of nutritional, psychological and/or exercise modifications have not resulted in the return of menses,” Gordon said.
In developing the guideline, an Endocrine Society-appointed task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. The guideline was co-sponsored by the American Society for Reproductive Medicine, the European Society of Endocrinology and the Pediatric Endocrine Society, whose members reviewed preliminary drafts.
To diagnose hypothalamic amenorrhea, health care providers must rule out other conditions that can halt menstruation, including benign tumors in the pituitary gland and adrenal gland disorders. The guideline recommends that providers first exclude pregnancy as a cause and then perform a full physical exam to evaluate for other potential causes. Levels of estrogen, thyroid hormones and prolactin should be measured to help identify factors preventing menstruation, the authors noted.
Patients with hypothalamic amenorrhea who have an abnormally slow heart rate, low blood pressure or an electrolyte imbalance should be evaluated for inpatient treatment, according to the guideline. Careful monitoring is needed in these cases because there is a high mortality rate associated with hypothalamic amenorrhea in the setting of eating disorders, particularly anorexia nervosa.
Select patients presumed to have hypothalamic amenorrhea should undergo a brain MRI to check for pituitary gland abnormalities or pituitary hormone deficiencies. These include patients with a history of severe or persistent headaches, persistent vomiting that is not self-induced, changes in vision, thirst or urination not attributable to other causes, or neurologic signs suggesting a central nervous system abnormality.
In treating functional hypothalamic amenorrhea, options for improving energy balance include increased caloric consumption, improved nutrition or decreased exercise activity; this often requires weight gain, according to the researchers. Psychological support, such as cognitive behavioral therapy, is also recommended. Oral contraceptive pills are not recommended for the sole purpose of regaining menses or improving bone mineral density.
The guideline aims to dispel “myths of management” regarding functional hypothalamic amenorrhea, Gordon said. Combined oral contraceptive pills, for example, do not confer bone protection in these patients, but they continue to be prescribed by clinicians solely for this purpose, she noted.
“The accumulating evidence on this subject led us to recommend short-term, transdermal estrogen therapy to select patients when amenorrhea is longstanding despite efforts to correct their ‘energy deficit,’” Gordon said. “We emphasize that the mainstay of therapy for these patients remains close attention to nutrition, exercise and alleviating stressors through psychological support, best achieved through a multidisciplinary team.”
The guideline also aims to provide guidance around the appropriate evaluation for patients who present with functional hypothalamic amenorrhea, as there has been a lack of consistency in current clinical practice, she said.
“Functional hypothalamic amenorrhea is a ‘diagnosis of exclusion,’ meaning that underlying anatomic or organic pathologies must first be ruled out,” Gordon said. “Our guideline attempts to provide clarity around the appropriate general, endocrine and imaging evaluations to consider for these patients.”
The guideline was published online and will appear in the May issue of The Journal of Clinical Endocrinology & Metabolism. – by Regina Schaffer
Disclosure: Gordon reports being a member of the data safety monitor board for Janssen Pharmaceuticals, serving as a consultant for the Department of Justice, Health Resources and Services Administration and a council member of the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development. Please see the full guideline for the other authors’ relevant financial disclosures.
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