creation date: 2026-01-19 17:42
tags: Pathologies
Functional Hypothalamic Amenorrhea
Background
Definitions
Functional hypothalamic amenorrhea (FHA) refers to amenorrhea due to hypogonadotropic hypogonadism (secondary hypogonadism) which occurs from low energy availability or stress.
This is responsible for approximately 30% of secondary amenorrhea and 3% of primary amenorrhea.
Etiology
Low energy availability can occur from:
Decreased caloric intake (relative to expenditure):
- Eating disorders, particularly anorexia nervosa
- Specific dietary restrictions (low fat, high fibre and carbs associated with FHA)
- Malabsorption (eg. celiac)
Excessive energy expenditure: - Excessive exercise
- Stress (emotional stress may be a cause and effect, resulting in positive feedback loop)
Pathophysiology
Low energy availability and a relative state of energy deficit can suppress the hypothalamic-pituitary-ovarian (HPO) axis, diverting energy away from the reproductive processes to more vital systems. This results in:
- Less frequent or low amplitude LH pulse
- Decrease in GnRH secretion and subsequent LH and FSH secretion
Disruption in the HPO axis results in dysregulation of the menstrual cycle.
Clinical Presentation
Signs & Symptoms
The primary symptom is amenorrhea.
Additional clinical findings are manifestations of estrogen deficiency which may manifest as:
- Low bone density/fractures
- Anovulatory infertility
- Vaginal dryness and dysparenunia
History & Physical Exam
History should elicit:
- Presence of previously normal cycles that became irregular and then ceased
- Irregularity/cessation coincided with weight loss, increased activity, or significant stress
- Possibility of pregnancy
- Past medical history or symptoms suggestive of inflammatory bowel disease, celiac disease, thyroid disease, primary ovarian insufficiency, PCOS, NCCAH, hyperprolactinemia, hypopituitarism, etc.
Physical exam should include assessment of external and internal genitalia including assessment of vaginal mucosa. Bimanual exam is typically deferred in adolescents who are not sexually active.
Risk factors
Diagnosis
Criteria
FHA is a diagnosis of exclusion. Diagnosis can be made clinically if a precipitating event resulted in new-onset amenorrhea and other causes have been ruled out.
Work-up
The workup consist of ruling out alternative causes of (typically) secondary amenorrhea and assessment of complications.
Ruling out alternative diagnoses
Labs typically consist of:
- b-hCG
- Prolactin
- TSH, T4
- FSH, LH, E2
Ultrasound may be indicated if uterine or uterine outflow tract disorders are suspected.
If hypogonadotropic hypogonadism is unexplained (no precipitating events) or if CNS symptoms are present, MRI is indicated.
Assessment of complications
Bone density testing should be performed if amenorrhea has been present for >6 months via dual-energy x-ray absorptiometry. Further workup may be indicated if BMD is low.
Anxiety and mood disorder screening should be performed as needed.
Anovulatory infertility typically resolves with recovery from FHA but infertility assessment should be performed if not.
Differential
Differential is discussed separately.
Red Flags / Complications
Complications include:
- Low bone density/fractures
- Anovulatory infertility
- Dysparenunia
- Cardiovascular effects (lipids, endothelium, risk of CAD)
- Anxiety
Management
Treatment of Underlying Cause
Treatment generally involves reversal of the inciting factor whether that be insufficient caloric intake, excessive exercise, or stress. This may require a multi-disciplinary approach including:
- Dietitian
- Cognitive behavioural therapy or other types of therapy
- Stress reduction
For some patients, they may just be unaware of the cause and counselling the need for matching caloric intake-energy expenditure is sufficient.
In many cases, especially long-standing FHA, in-patient management is necessary. Primary concerns of management include:
- Adequate nutrition
- Refeeding syndrome due to increase in intake (eg. cardiovascular collapse, hypophosphatemia)
Treatment of Complications
Concurrently with treatment of underlying cause, additional management may be indicated.
Anovulatory infertility and sexual function
Adjunctive treatment of infertility is not recommended until a healthy weight has been achieved as adequate caloric intake is crucial for minimizing obstetric complications.
For vaginal dryness and dyspareunia, topical estrogen may be considered.
Low bone density
Initial supplementation should include:
- 1200-1500 mg calcium daily
- Vitamin D
In cases where lifestyle management is insufficient in return of menses, hormonal therapy is indicated.
- Transdermal estradiol with cyclic progestin