Evaluate bone health no longer than 6 months after onset of functional hypothalamic amenorrhea (FHA), according to new guidance on its diagnosis and management.
The preferred measure of bone mineral density (BMD) is dual-energy x-ray absorptiometry (DXA), guidance lead author Catherine M. Gordon, MD, of Cincinnati Children’s Hospital Medical Center noted in an interview.
“Our group has tried to raise awareness with our guideline about bone health,” said Dr. Gordon. “Bone is unfortunately detrimentally affected in adolescents and adult women with FHA, [so] our guideline now formally recommends bone density screening after 6 months of amenorrhea.”
Among the available therapies to preserve or restore bone density is short-term use of transdermal E2 therapy, with cyclic oral progestin, only after conventional intervention with nurtritional and exercise modification has been attempted for a “reasonable” amount of time but menstrual cycles have not yet been reestablished. Bisphosphonates, denosumab, testosterone, and leptin also can be used to improve bone mineral density (BMD), with recombinant parathyroid hormone 1-34 (rPTH) recommended in rare cases of extremely low BMD.
“Patients should not use oral contraceptives as a way to induce menstruation or improve BMD,” she said.
“We anticipate that some clinicians will be surprised to see that combined oral contraceptive pills do not provide bone protection for patients with FHA,” Dr. Gordon explained. “Our guideline reviews data on this point, which led to our recommendation that short-term transdermal estrogen may be helpful in restoring menses for select patients with longstanding amenorrhea despite efforts to correct their ‘energy deficit.’ ”
Clinicians also should be aware that FHA can mask the signs and symptoms of polycystic ovary syndrome in some young women. It’s therefore important for providers to understand that a patient could carry both diagnoses: Such patients should have a baseline BMD measurement taken, along with “clinical monitoring for hyper-response in those treated with exogenous gonadotropins for infertility,” according to the guidelines.
In general, “FHA is a ‘diagnosis of exclusion,’ meaning that underlying anatomic or organic pathologies must first be ruled out. It is important to consider other etiologies first before the amenorrhea is attributed to inadequate intake, overexercise, or stress,” Dr. Gordon said.
According to the guidelines, patients should only undergo evaluation for FHA if menstrual cycle interval exceeds 45 days on a consistent basis, or if they present with amenorrhea for at least 3 months. Patients with suspected FHA should be screened for psychological stressors that could be inducing anovulation.
When trying to make a diagnosis of FHA, providers should be “obtaining a detailed personal history with a focus on diet; eating disorders; exercise and athletic training; attitudes, such as perfectionism and high need for social approval; ambitions and expectations for self and others; weight fluctuations; sleep patterns; stressors; mood; menstrual pattern; fractures; and substance abuse,” the guidelines state.
Family histories also should be evaluated, and patients should undergo a full physical. Once a diagnosis of FHA is made, however, clinicians should help educate patients about different menstrual cycles while letting women know that an irregular cycle does not necessarily prevent them from conceiving.
The most important aspect of managing FHA is to take a multidiscipinary approach, according to Dr. Gordon and her colleagues (J Clin Endocrinol Metab. May 2017;102:1-27).
“We emphasize that the mainstay of therapy for these adolescents and women is close attention to nutrition, exercise, and alleviating stressors through psychological support, best achieved through a multidisciplinary team,” Dr. Gordon stated.
Any patient diagnosed with FHA who also develops severe bradycardia, hypotension, orthostasis, or electrolyte imbalance should be treated as an inpatient. Energy imbalances can affect the hypothalamic-pituitary-ovarian (HPO) axis function, so correcting that should be considered a priority.
Adolescents and women for whom pregnancy has been excluded are recommended to undergo a progestin challenge, which should indicate chronic estrogen exposure via induced withdrawal bleeding. A brain MRI also can be conducted if the patient complains about chronic headaches, vomiting, or problems with vision or thirst.
FHA patients who wish to conceive have a number of options outlined by the guidelines. Pulsatile gonadotropin-releasing hormone (GnRH) should be the first treatment, followed by gonadotropin therapy, which must be administered as carefully as possible. Clomiphene citrate also can be used in certain situations, and cognitive behavior therapy is also a viable option, although the guidelines note that only one relatively small study offered any evidence of its efficacy. Kisspeptin and leptin should not be used as a treatment for infertility under any circumstances.
These guidelines were created in conjunction with the American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. An evidence-based approach was undertaken by a panel of eight experts, a methodologist, and a medical writer.
“There is currently a lack of consistency in clinical practice regarding the evaluation for patients with FHA,” said Dr. Gordon. “Our guideline attempts to clarify for clinicians what the appropriate general, endocrine, and imaging work-up would entail.”
The creation of these guidelines was funded by the Endocrine Society.