How does anorexia (eating disorder) cause oligomenorrhea (infrequent menstrual periods)?

Mechanism of Oligomenorrhea in Anorexia Nervosa

Anorexia nervosa causes oligomenorrhea primarily through disruption of the hypothalamic-pituitary-gonadal axis due to severe energy deficiency, leading to decreased GnRH pulsatility and subsequent reduction in gonadotropin secretion. 1

Pathophysiological Pathway

Energy Deficiency as the Primary Trigger

Anorexia nervosa creates a state of severe energy deficiency (low energy availability), which triggers a cascade of hormonal changes designed to conserve energy:

• Energy availability below 30 kcal/kg fat-free mass per day has been shown to discriminate between amenorrheic versus eumenorrheic status in women 1
• This energy deficit represents an evolutionary response to food scarcity, prioritizing survival over reproduction 1

Hypothalamic-Pituitary-Gonadal Axis Disruption

The low energy state disrupts normal hypothalamic function through several mechanisms:

1. Altered GnRH Secretion:

   • Disrupted gonadotropin-releasing hormone (GnRH) pulsatility from the hypothalamus 1
   • This altered pulsatility directly affects luteinizing hormone (LH) secretion patterns

2. Gonadotropin Suppression:

   • Decreased LH and FSH release from the pituitary 1
   • Irregular or absent pulses of these hormones fail to properly stimulate the ovaries

3. Estrogen Deficiency:

   • Reduced ovarian stimulation leads to decreased estradiol production 1
   • Systemic reductions in estradiol contribute to menstrual irregularity 1

Hormonal Mediators of Energy Status

Several hormones act as signals between nutritional status and reproductive function:

1. Leptin Deficiency:

   • Leptin (produced by adipose tissue) is significantly reduced in anorexia 1, 2
   • Low leptin levels signal energy insufficiency to the hypothalamus
   • Studies show eumenorrheic women with anorexia have higher leptin levels than amenorrheic women of similar weight 2

2. Other Hormonal Alterations:

   • Increased cortisol levels 1, 3
   • Decreased insulin-like growth factor 1 (IGF-1) 1, 2
   • Decreased total and free triiodothyronine (T3) 1
   • Decreased free thyroxine (T4) 1
   • Increased ghrelin and adiponectin 1
   • Increased peptide YY 1

Body Composition Factors

Fat mass plays a critical role in maintaining menstrual function:

• Women with anorexia who maintain menses have significantly higher body fat percentage than those with amenorrhea (despite similar BMI) 2, 3
• Studies show eumenorrheic women with anorexia have approximately 20.9% body fat versus 16.7% in amenorrheic women 2
• Fat distribution, particularly truncal fat, may be especially important for reproductive function 2

Clinical Implications

Spectrum of Menstrual Disturbances

• Menstrual dysfunction in anorexia exists on a continuum:
  • Subclinical menstrual defects (luteal phase defects, anovulation)
  • Oligomenorrhea (infrequent periods)
  • Secondary amenorrhea (absence of menses for ≥3 consecutive cycles) 1
  • Primary amenorrhea (if anorexia occurs before menarche)

Recovery Considerations

• Weight restoration alone may not be sufficient to restore normal menstrual function:
  • Approximately 14% of women with anorexia remain amenorrheic despite weight recovery 3
  • Both adequate body composition and normalized hormonal patterns are necessary 3
  • Persistent disordered eating behaviors and excessive exercise can maintain amenorrhea despite weight gain 4

Long-term Health Consequences

• Persistent oligomenorrhea/amenorrhea leads to:
  • Decreased bone mineral density and increased fracture risk 1, 2
  • Endothelial dysfunction and poor lipid profiles 1
  • Potential long-term reproductive consequences 1

Common Pitfalls in Understanding and Management

• Focusing only on weight: Body composition (especially fat mass) is more important than weight alone 2
• Overlooking exercise: Excessive physical activity can maintain menstrual dysfunction despite weight recovery 3
• Ignoring psychological factors: Persistent disordered eating attitudes can contribute to ongoing menstrual dysfunction 4
• Assuming immediate recovery: Hormonal normalization may lag behind weight restoration 3

The restoration of normal menstrual function in anorexia requires addressing the underlying energy deficit, achieving adequate body fat percentage, normalizing hormonal patterns, and resolving psychological aspects of the eating disorder.