Functional Hypothalamic Amenorrhea Diagnosis and Treatment Guidelines Released

The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society have issued a guideline detailing recommendations for diagnosing and treating functional hypothalamic amenorrhea (FHA).

The guideline, “Functional hypothalamic amenorrhea: an Endocrine Society clinical practice guideline,” was published online and will appear in the May issue of the Journal of Clinical Endocrinology & Metabolism.¹

According to the guideline, FHA is a form of chronic anovulation that is not a result of identifiable organic causes; rather, it is associated with stress, weight loss, excessive exercise, or a combination of the 3.

FHA often affects adolescent girls or women with low body weight, a low percentage of body fat, a very low caloric or fat intake, and emotional stress. Those at risk are girls or women who burn more calories through exercise than they consume in their diet, and may include ballet dancers, figure skaters, and runners.

Hypothalamic amenorrhea increases the risk for delayed puberty in adolescent girls and infertility in adult women. Furthermore, chronic hypothalamic amenorrhea may contribute to bone loss and stress fractures and is associated with a high risk for osteoporosis development. 

Finding and Addressing the Underlying Cause

In a press release from the Endocrine Society, Catherine M. Gordon, MD, guideline task force chair with the Cincinnati Children’s Hospital Medical Center in Ohio, said healthcare providers must address the energy imbalance to effectively treat hypothalamic amenorrhea, which typically requires behavioral modifications.²

“Referring patients to a nutritionist for specialized dietary instructions is an extremely important part of their care,” Dr Gordon said in the release. “Menstrual cycles can often be restored with increased calorie consumption, improved nutrition or decreased exercise activity.” 

In the guideline, Dr Gordon and fellow Endocrine Society task force members state that FHA is a diagnosis of exclusion. Healthcare providers must rule out other conditions that can halt menstruation, such as benign tumors in the pituitary gland and adrenal gland disorders. The authors also recommend excluding pregnancy as a cause, performing a full physical exam to assess for other potential causes, and obtaining general laboratory test results (eg, complete blood count and electrolytes) as part of the screening process. 

The guidelines also indicate that patients with FHA should be evaluated for inpatient treatment if they have severe bradycardia, hypotension, orthostasis, or an electrolyte imbalance. Because there is a high mortality rate associated with hypothalamic amenorrhea in the setting of eating disorders, particularly anorexia nervosa, careful monitoring is necessary.

In addition, the authors recommend that patients presumed to have FHA undergo brain magnetic resonance imaging to check for pituitary gland damage or abnormalities or pituitary hormone deficiencies if they exhibit the following signs or symptoms:

• 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
• Neurological signs indicating a central nervous system abnormality
• Other clinical signs or test results suggesting pituitary hormone deficiency or excess

More Data Needed

Moving forward, Dr Gordon and coauthors wrote that more research into the treatment of amenorrhea and low bone mineral density in FHA is needed, “with careful consideration of the effects on weight and body composition and the need for appropriate dosing adjustments.” They added, “[W]e need more research regarding the impact of FHA on other body systems and neural function.”

Disclosures

The guideline was funded by the Endocrine Society. Dr Gordon reports being a member of the data safety monitoring board for Janssen Pharmaceuticals. See the study online for a full list of author disclosures.

References

1. Gordon CM, Ackerman KE, Berga SL, et al. Functional hypothalamic amenorrhea: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(5):1-27. doi:10.1210/jc.2017-00131
2. Endocrine Society experts issue Clinical Practice Guideline on hypothalamic amenorrhea [press release]. Washington, DC: Endocrine Society. https://www.endocrine.org/news-room/current-press-releases/endocrine-society-experts-issue-clinical-practice-guideline-on-hypothalamic-amenorrhea. Published March 22, 2017. Accessed April 26, 2017.