Common Questions

What is the mechanism of amenorrhea in anorexia nervosa?

Anorexia nervosa commonly results in functional hypogonadotropic hypogonadism. The mechanism by which this occurs is believed to be the same mechanism that occurs when other stressors are placed on the body.

In times of great stress, corticotropin-releasing hormone (CRH), produced in the hypothalamus, is suppressed. The suppression of CRH results in suppression of hypothalamic gonadotropin-releasing hormone (GnRH), which in turn results in suppression of luteinizing hormone (LH) and follicular-stimulating hormone (FSH) from the pituitary gland. When these pituitary hormones are suppressed, the production of estradiol from the ovaries is suppressed, resulting in hypogonadism. The name hypogonadotropic hypogonadism refers to the suppression of GnRH from the hypothalamus, which indirectly leads to a hypoestrogenemic state (1,2). The degree of low bone density in anorexia nervosa, however, is more severe than that seen in other women with hypothalamic amenorrhea matched for age and duration of amenorrhea suggesting other nutritional factors may be contributing (3).

Female Hypogonadotropic Hypogonadism
Category Examples Treatment
Functional Exercise, dieting, stress, eating disorder Treat the underlying disorder.
Structural lesions of the hypothalamus Tumors Infiltrative disorders (i.e., sarcoid, hemachromatosis) Head trauma Treat the underlying disorder.
Isolated defect in GnRH secretion Idiopathic hypogonadatropic hypogonadism (can be congenital or adult onset) If fertility is desired, treat with intravenous pulsatile GnRH administration, otherwise estrogen replacement.
Partial defect in GnRH secretion Delayed puberty If very delayed, consider starting therapy with unopposed estrogen to allow breast development, then add a progestin.
Chart adapted from "Hypogonadotropic Hypogonadism, "Endocrinology and Metabolism Clinics of North America. Volume 27(4), December 1998, pp. 739-761
  1. Chrousos GP, Torpy DJ, Gold WB. Interactions between the hypothalamic-pituitary adrenal axis and the female reproductive system: Clinical implications. Annals of Internal Medicine 1998; 129(3): 229-238.
  2. Hayes FJ, Seminara SB, Crowley WF. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 1998; 27(4): 739-763.
  3. Grinspoon, S, Miller K, Coyle C et al. Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea. Journal of Clinical Endocrinology and Metabolism 1999; 84: 2049-2055. Available online.
Last updated 2012-03-27

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