Cause of Low FSH and LH in Underweight Females

Primary Mechanism: Energy Deficit and Hypothalamic Suppression

Low FSH and LH levels in underweight females 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, 2
The LH to FSH ratio typically falls below 1 in approximately 82% of FHA patients, which is diagnostically useful 1

The problem in FHA is central (hypothalamic), not ovarian 3
Gonadotropins are low or low-normal, not elevated, in FHA 2
Pulsatile GnRH administration can restore ovulation, proving the ovaries are functional in FHA 3

The Endocrine Society recommends that BMI should reach ≥ 18.5 kg/m² before ovulation induction is offered 1, 3
Weight restoration is the primary therapeutic intervention for FHA 1
Clomiphene citrate is not recommended as first-line treatment for FHA due to uncertain efficacy and lack of randomized trials 1

Poor nutrition disrupts the hypothalamic-pituitary-gonadal axis, leading to decreased LH pulsatility while FSH secretory patterns remain relatively preserved, ultimately causing menstrual dysfunction through reduced estradiol and progesterone rather than elevated gonadotropins 4, 5, 6
LH is preferentially suppressed through disrupted GnRH pulsatility when energy availability falls below critical thresholds 5, 6
FSH levels remain relatively stable or may even show minimal changes during nutritional deficiency 4

When energy availability drops below 30 kcal/kg fat-free mass per day, hormonal alterations occur, including decreased estradiol 7, decreased progesterone 5, decreased leptin 5, increased ghrelin and cortisol 5, decreased insulin and IGF-1 5, and decreased thyroid hormones (T3, T4) 5

Primary ovarian insufficiency (POI) is characterized by elevated FSH and LH due to ovarian failure 8
Menopause is the natural cessation of ovarian function with high FSH 9
Ovarian damage from chemotherapy, radiation, or surgery causes elevated FSH 9
Functional hypothalamic amenorrhea (FHA) from poor nutrition shows low-to-normal FSH with suppressed LH 6, 8

Proper characterization of FSH levels requires overnight blood sampling at minimum 3 times per hour (preferably 6 times per hour) due to pulsatile release patterns 4, 10

Low calcium, magnesium, selenium, iron, phosphorus, zinc, and vitamins B3, B12, D, E, and folate intake are associated with restrictive dietary patterns, and may have implications for FSH levels, although direct correlations are less established than for sodium and manganese, in the general population, according to the Nutrition Research Reviews 11, 12

Excessive exercise can cause low estradiol levels in female athletes, primarily through the mechanism of low energy availability (EA) that disrupts the hypothalamic-pituitary-gonadal axis, leading to suppressed GnRH pulsatility, menstrual dysfunction, and systemically reduced estradiol concentrations, as recommended by the American College of Sports Medicine 13, 14
Low EA (defined as <30 kcal/kg fat-free mass per day) causes disruptions in LH pulsatility, which serves as a surrogate for GnRH pulsatility, ultimately disturbing gonadotropin release and causing menstrual dysfunction manifested as oligo-amenorrhea, according to the International Olympic Committee 13, 14
Irregular or absent menses, combined with abnormal pituitary signaling, causes systemic reductions in estradiol, as stated by the Endocrine Society 13, 14
Low EA causes the following hormonal changes in exercising women: decreased estradiol, decreased progesterone, decreased leptin, increased ghrelin, increased cortisol, decreased insulin, decreased thyroid hormones (T3, T4), and decreased IGF-1, as reported by the American College of Sports Medicine 13, 15, 16
Even 5 days of reduced EA (10-30 kcal/kg FFM·day⁻¹) demonstrated decreased levels of estradiol in eumenorrheic young women, which may have led to menstrual dysfunction with extended study duration, according to the National Institutes of Health 15, 14

Estradiol is an osteoprotective agent that inhibits osteoclast activity, and when estrogen levels are aberrantly subphysiologic, osteoclast activity predominates and bone mass is lost, as stated by the American College of Sports Medicine 13, 14
Oligo-amenorrhea decreases trabecular number and cortical thickness, leading to decreased bone mineral density and increased incidence of bone stress injury, according to the International Olympic Committee 13, 14
Hypoestrogenism in oligo-amenorrhea induces a post-menopausal-like physiology: endothelial dysfunction, poor lipid profiles (elevated LDL, total cholesterol, triglycerides), and renin-angiotensin-aldosterone axis changes, as reported by the American Heart Association 15, 16
Adolescent female swimmers with ovarian suppression (lower estradiol and progesterone) had a 9.8% increase in time (worse performance) versus 8.2% improvement in eumenorrheic swimmers over 12 weeks, according to the American College of Sports Medicine 17
Target energy availability of approximately 45 kcal/kg FFM·day⁻¹ is likely ideal for endurance athletes to maintain body mass and fuel high levels of training with fitness and performance improvements, as recommended by the International Society of Sports Nutrition 17, 18