Endocrine Society's Clinical Practice Guideline (2017): FHA (Functional Hypothalamic Amenorrhea)
M3 India Newsdesk Sep 19, 2017
The Endocrine Society has recently issued recommendations for diagnosing and managing Functional Hypothalamic Amenorrhea (FHA), a common disorder of adolescence.
Functional hypothalamic amenorrhea (FHA), a common cause of secondary amenorrhea, results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone).
Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.
The Endocrine Society has issued clinical practice guidelines for diagnosis, evaluation, and treatment of FHA earlier this year.Here are the key points.
- FHA is a diagnosis of exclusion.Clinicians only make the diagnosis of functional hypothalamic amenorrhea (FHA) after excluding the anatomic or organic pathology of amenorrhea
- Adolescents and women whose menstrual cycle persistently exceed 45 days and /or those who have amenorrhea for 3 months or more should be diagnosed for FHA.
- Screen the patients for psychological stressors.
- Educate the patients about the various menstrual patterns that may occur during the recovery phase, once the diagnosis of FHA is established.
- Obtain the patient's detailed personal history with a focus on eating disorders and diet, exercise and athletic training, sleep pattern, stressors, mood, menstrual pattern, fractures and substance abuse. The family history of the patient with disorders related to eating and reproduction should be noted.
- Rule out pregnancy and later perform complete physical examination to establish the cause of FHA
- Perform these screening tests - beta-human chorionic gonadotrophin, complete blood count, electrolytes, glucose, bicarbonate blood urea nitrogen, creatinine, liver panel and sedimentation rate and/or C-reactive protein levels.
- Carry out these endocrine evaluation tests - TSH, T4, LH, FSH, estradiol (E2) and anti-Mullerian hormone (AMH). Total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels in patients with clinical hyperandrogenism and 17-hydroxyprogesterone levels at 8 am if late onset of Congenital Adrenal Hyperplasia (CAH) is suspected.
- Administer a progestin challenge, after excluding pregnancy
- An MRI for patients with a history of severe headaches, persistent vomiting, change in vision, thirst or urination, lateralizing neurological signs or reports that suggest pituitary hormone deficiency or excess is suggested.
- Get bone mineral density (BMD) measurement if amenorrhea exists for 6 months or more, by dual energy X-ray absorptiometry (DXA).
- Evaluation of Mullerian tract anomalies is suggested in case of primary amenorrhea including diagnostic options such as physical examination, progestin challenge test, abdominal or transvaginal ultrasound and/or MRI.
- In patients with underlying Polycystic Ovary Syndrome (PCOS), a baseline BMD with DXA should be advised and clinical monitoring for hyper response in patients treated with exogenous gonadotropins for infertility is suggested.
- Evaluate patients for inpatient treatment who have FHA and severe bradycardia, hypotension, orthostasis and/or electrolyte imbalance.
- Correct energy balance to improve hypothalamic-pituitary-ovarian (HPO) axis..by improvement options such as increased calorie consumption, improved nutrition and decreased exercise activity should be considered Psychological support such as cognitive behavior therapy (CBT) should be used.
- Oral contraceptive pills (OCPs) to be used solely for regaining menses and improving BMD.
- Patient education regarding the use of OCPs for contraception, that it may mask the return of spontaneous menses and bone loss may continue.
- Use of transdermal E2 therapy with cyclic oral progestin in patients who have not had return of the menses after a reasonable trial of nutritional, psychological and exercise modification.
- BMD can be improved using biphosphonates, denosumab, testosterone, and leptin.
- Short-term use of recombinant parathyroid hormone1-34(rPTH) is an option in the setting of delayed fracture healing and low BMD, in rare adult FHA cases.
- After a complete fertility workup for patients wishing to conceive, it is suggested; To treat with pulsatile gonadotrophin releasing hormone (GnRH) initially, followed by gonadotrophin therapy and induction of ovulation when GnRH is not available.
- Gonadotrophin therapy to be used cautiously.
- If the patient has sufficient endogenous estrogen levels, ovulation induction with clomiphene citrate can be used for treatment trial.
- The use of kisspeptin and leptin for treating infertility is discouraged.
- A trial of CBT should be considered as it has the potential to restore ovulatory cycles and fertility.
- Induction of ovulation is an option only when the patient’s BMI is at least 18.5kg/m² and should be considered only after attempts to normalize energy balance.
Apart from anovulation and infertility, several other health issues arise with FHA such as disturbances in the skeletal system, cardiovascular system, and mental problems. A decrease in bone mass density is also attributed to this disorder, which may make the patient prone to bone fractures. A decreased bone density is indicative of osteopenia and osteoporosis as long-term complication of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in lipid profile.
Patients diagnosed with FHA should be managed in a way that can address both short-term and long-term medical consequences.
Reference: Gordon CM et al. Functional hypothalamic amenorrhea: An Endocrine Society clinical practice guideline.J Clin Endocrinol Metab 2017 Mar 22; [e-pub].
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