What is functional hypothalamic amenorrhea (FHA) in young, athletic, or stressed women?

Functional Hypothalamic Amenorrhea (FHA)

Definition

Functional hypothalamic amenorrhea is a reversible neuroendocrine condition caused by chronic anovulation due to functional suppression of pulsatile GnRH secretion at the hypothalamic level, resulting in decreased LH and FSH release, hypoestrogenism, and cessation of menstruation—without any identifiable organic pathology. 1

Pathophysiology

The core mechanism involves disruption of the hypothalamic-pituitary-ovarian axis:

• Reduced GnRH pulsatility leads to decreased LH pulse frequency and amplitude, with LH affected more than FSH (since slow GnRH pulses actually favor FSH secretion) 1
• This results in low or low-normal serum LH and FSH levels, typically with an LH:FSH ratio <1 in approximately 82% of cases 2
• Hypoestrogenism develops due to absent ovarian follicle recruitment and lack of ovulation 1, 3
• Exogenous pulsatile GnRH administration can restore normal ovulatory function, confirming the functional (not structural) nature of the disorder 1

Kisspeptin neurons appear to bridge the hypothalamic-pituitary-adrenal axis (stress response) and the hypothalamic-pituitary-gonadal axis, explaining the stress-amenorrhea connection 1

Epidemiology and Prevalence

• FHA accounts for 20-35% of all secondary amenorrhea cases and approximately one-third of secondary amenorrhea in women of reproductive age 1, 4
• It represents 3% of primary amenorrhea cases 1
• Secondary amenorrhea overall affects 3-4% of women in the general population 1, 4
• Prevalence is dramatically higher in specific populations: up to 69% in dancers and collegiate long-distance runners 1

Triggering Factors

FHA results from three primary stressors, often occurring in combination 1:

• Energy deficit/caloric restriction: Energy availability below 30 kcal/kg fat-free mass/day disrupts LH pulsatility 1, 5
• Excessive exercise: Particularly endurance training combined with inadequate energy intake 1
• Psychological stress: Including psychosocial stressors and psychological disorders 1
• Weight loss: Rapid or significant fat mass reduction, even over one month, can compromise menstrual function 1

The exact duration of stress needed to cause amenorrhea remains unclear, though the temporal relationship between stressor onset and amenorrhea is diagnostically significant 1, 2

Diagnostic Criteria

FHA is a diagnosis of exclusion requiring both clinical and laboratory findings 4, 6:

Hormonal Profile

• Low or low-normal LH and FSH (can be <2 IU/L in severe cases, though typically low-normal range) 4, 2
• LH:FSH ratio approximately 1.0 or less (ratio <1 in 82% of cases) 2
• Low estradiol levels indicating hypoestrogenism 2
• Normal or low testosterone with very low Free Androgen Index 2
• Elevated SHBG (higher than in PCOS patients) 2
• Normal prolactin and TSH to exclude other causes 4, 7

Clinical Features

• Clear history of one or more FHA triggers (energy deficit, excessive exercise, psychological stress) 2
• Thin endometrium on ultrasound reflecting estrogen deficiency 2
• Normal insulin sensitivity with low insulin levels (contrasting with PCOS) 2
• Lean body habitus or low-normal BMI 2

Critical Diagnostic Pitfall: FHA-PCOM

41.9-47% of women with FHA have polycystic ovarian morphology (PCOM) on ultrasound, creating a diagnostic trap that can lead to misdiagnosis as PCOS. 4, 2

Key differentiators between FHA-PCOM and PCOS:

• **LH:FSH ratio <1** in FHA-PCOM versus >2 in PCOS 2
• Higher SHBG levels in FHA-PCOM 2
• Clear history of energy deficit or stress in FHA-PCOM 4, 2
• Negative or thin endometrium despite PCOM appearance 2
• Very low Free Androgen Index in FHA-PCOM 2

Health Consequences

Immediate and Short-Term

• Infertility due to anovulation 6
• Nutrient deficiencies including anemia 1
• Chronic fatigue and increased infection risk 1
• Psychological impact including anxiety about normalcy and conception 1

Long-Term Complications

• Decreased bone mineral density: Hypoestrogenism during adolescence impairs peak bone mass accrual 1, 8
• Osteopenia and osteoporosis: High risk due to prolonged estrogen deficiency 7, 8
• Increased fracture risk: Particularly stress fractures in athletes 1, 8
• Cardiovascular risk: Long-term estrogen deficiency affects cardiovascular health 6
• Cognitive effects: Potential impact on mental health and cognition 6
• Persistent microarchitectural bone deficits may remain even after weight restoration 8

Management Approach

First-Line Treatment: Lifestyle Modification

The primary intervention focuses on correcting the underlying energy imbalance and removing stressors. 5, 9

Nutritional Rehabilitation

• Increase energy availability to ≥30 kcal/kg fat-free mass/day 5
• Add approximately 350 kcal/day to current intake 9
• Ensure regular meals throughout the day to maintain glucose availability (glucose affects LH pulses, T3, and cortisol) 5
• Increase body fat percentage above 22% may be required for menstrual restoration 5
• Each 1 kg increase in body fat mass increases likelihood of menstruation by 8% 5

Exercise Modification

• Reduce training intensity or volume (not complete cessation) 5
• Address Relative Energy Deficiency in Sport (RED-S) in athletes 7

Psychological Support

• Cognitive-behavioral therapy 5
• Stress management counseling 7
• Screen for and treat eating disorders 7, 5

Timeline for Recovery

• Menstrual function can be restored in 1-12 months with appropriate intervention 9
• However, long-term impact of nutritional intervention alone remains unclear 9

Hormonal Therapy Considerations

For refractory cases or when lifestyle modification is insufficient:

• Transdermal estrogen therapy shows promise for bone health in adolescents 8
• Oral contraceptives have limited skeletal benefits compared to transdermal estrogen 8
• Estrogen replacement therapy may be necessary to prevent long-term complications, particularly bone loss 7
• DXA scan for bone mineral density is recommended if amenorrhea persists >6 months 7

Special Population: Athletes

Athletes with FHA require evaluation for Relative Energy Deficiency in Sport (RED-S), which encompasses multiple physiological systems beyond just menstrual function 1, 7:

• Cardiovascular, gastrointestinal, endocrine, reproductive, skeletal, renal, and central nervous system effects 1
• Primary amenorrhea in collegiate athletes: 7% overall, 22% in cheerleading/diving/gymnastics 1
• Early identification is essential to optimize long-term skeletal and reproductive outcomes 8

Common Clinical Pitfalls

• Do not assume all amenorrhea in athletes or stressed women is benign—other pathology must be excluded 7
• Do not misdiagnose FHA-PCOM as PCOS based solely on ultrasound appearance 4, 2
• Do not overlook eating disorders—adolescents may minimize or deny disordered eating behaviors 7
• Do not rely solely on progestin challenge test—up to 60% of FHA patients may still have withdrawal bleeding 2
• Focus on body composition, not just body weight in treatment monitoring 5