Estrogen Deficiency in Anorexia Nervosa

Mechanism of Estrogen Deficiency

Energy deficit disrupts GnRH pulsatility, which preferentially suppresses luteinizing hormone (LH) secretion while FSH remains relatively preserved, in patients with anorexia nervosa 1
Low LH levels fail to stimulate adequate ovarian estradiol production, leading to hypoestrogenism and amenorrhea, in individuals with anorexia nervosa 3, 2
The LH:FSH ratio typically falls below 1 in approximately 82% of patients with functional hypothalamic amenorrhea (FHA), the condition underlying anorexia-related estrogen deficiency 1
This is a functional, reversible problem—the ovaries remain capable of responding to appropriate hormonal stimulation, as demonstrated by successful ovulation induction with pulsatile GnRH therapy, in patients with anorexia nervosa 1

Decreased estradiol and progesterone are the primary reproductive hormone changes, in individuals with anorexia nervosa 3, 2
Metabolic hormones shift dramatically: decreased leptin, increased ghrelin, increased cortisol, decreased insulin and IGF-1, in patients with anorexia nervosa 3
Thyroid function becomes suppressed: decreased T3, decreased free T3, and decreased free T4, in individuals with anorexia nervosa 3
Growth hormone resistance develops with paradoxically increased GH but decreased IGF-1, contributing to stunted linear growth in adolescents with anorexia nervosa 3

Fracture risk is doubled compared to eumenorrheic women, in patients with anorexia nervosa 4

Endothelial dysfunction develops, with approximately one-third of FHA patients showing decreased reactive hyperemia index, in individuals with anorexia nervosa 5, 4, 6
Lipid profiles worsen with elevated LDL, total cholesterol, and triglycerides, in patients with anorexia nervosa 6
Long-term cardiovascular risk remains uncertain but cycle irregularities increase subsequent coronary heart disease risk, in individuals with anorexia nervosa 4

3-4 times increased risk of preterm birth, in pregnant women with anorexia nervosa 4
Increased risk of miscarriage, hyperemesis, cesarean section for severe fetal growth restriction, and small for gestational age babies, in pregnant women with anorexia nervosa 4

FHA shows LH:FSH ratio <1, while PCOS shows ratio >2, in patients with anorexia nervosa 1
Gonadotropins are low or low-normal in FHA, not elevated as in primary ovarian insufficiency, in individuals with anorexia nervosa 1
FHA patients lack the insulin resistance and elevated androgens characteristic of PCOS, in patients with anorexia nervosa 1

The Endocrine Society recommends BMI should reach ≥18.5 kg/m² before ovulation induction is offered, as weight restoration is the primary therapeutic intervention, in patients with anorexia nervosa 1
Baseline DEXA scan is recommended after ≥6 months of amenorrhea, or earlier with risk factors for osteoporosis, in individuals with anorexia nervosa 4