Cause of Low FSH and LH in Underweight Females
Low FSH and LH levels in an underweight female are caused by functional hypothalamic amenorrhea (FHA), where energy deficit and low body weight suppress the hypothalamic-pituitary-gonadal axis, leading to decreased GnRH pulsatility that preferentially reduces LH secretion while FSH remains relatively preserved. 1
Primary Mechanism: Energy Deficit and Hypothalamic Suppression
The fundamental cause is energy deficit disrupting the hypothalamic-pituitary-gonadal axis. 2 When energy availability drops below 30 kcal/kg fat-free mass per day, the hypothalamus reduces GnRH pulse frequency, which directly suppresses gonadotropin secretion. 2
- LH is preferentially and more severely suppressed through disrupted GnRH pulsatility when energy availability falls below critical thresholds. 2
- FSH levels remain relatively stable or show minimal changes during nutritional deficiency, as slow frequency GnRH pulses favor FSH secretion over LH. 1, 2
- The LH to FSH ratio typically falls below 1 in approximately 82% of FHA patients, which is diagnostically useful. 1
Associated Hormonal Changes in Underweight States
Beyond gonadotropins, multiple hormonal alterations occur in energy-deficient states: 2
- Decreased estradiol and progesterone (not elevated as in primary ovarian failure)
- Decreased leptin (signals energy deficit to hypothalamus)
- Increased ghrelin and cortisol (stress response activation)
- Decreased insulin and IGF-1 (metabolic suppression)
- Decreased thyroid hormones (T3, T4) (metabolic adaptation)
Key Diagnostic Features of FHA
The diagnosis can be safely assumed when typical causes are present alongside clear signs of estrogen deficiency. 1 The well-known causes include: 1
- Underweight status (BMI < 18.5 kg/m²)
- Caloric deficiency/energy deficit
- Excessive exercise
- Psychological stress
Low gonadotropin levels, especially LH, are characteristic for FHA. 1 Additional supportive findings include:
- Low endometrial thickness (indicates estrogen deficiency) 1
- Low-to-normal FSH with suppressed LH 2
- LH:FSH ratio < 1 in most cases 1
Critical Distinction from Other Conditions
This pattern differs fundamentally from primary ovarian insufficiency or menopause, where FSH and LH are elevated due to loss of negative feedback from the failing ovary. 2 In FHA:
- The problem is central (hypothalamic), not ovarian 1
- Gonadotropins are low or low-normal, not elevated 1
- Pulsatile GnRH administration can restore ovulation, proving the ovaries are functional 1
Clinical Pitfalls to Avoid
Do not confuse FHA with polycystic ovary syndrome (PCOS), even if polycystic ovarian morphology is present on ultrasound. 1 Key distinguishing features:
- PCOS shows LH:FSH ratio > 2, while FHA shows ratio < 1 1
- PCOS patients have higher testosterone and lower SHBG than FHA patients 1
- FHA patients lack insulin resistance, which is common in PCOS 1
The progestin challenge test has limited utility - up to 60% of FHA patients may have withdrawal bleeding, making it unreliable for diagnosis. 1 Endometrial thickness is a better indicator of estrogen status. 1
Management Implications
Weight restoration is the primary therapeutic intervention. 1 The Endocrine Society recommends:
- BMI should reach ≥ 18.5 kg/m² before ovulation induction is offered 1
- Once spontaneous menstrual cycles resume, allow spontaneous conception rather than immediate ovulation induction 1
- Clomiphene citrate is not recommended as first-line treatment for FHA due to uncertain efficacy and lack of randomized trials 1