What are possible metabolic causes of amenorrhea?

Updated: Oct 14, 2019
  • Author: Kristi A Tough DeSapri, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Both extreme thinness or rapid weight loss and morbid obesity or rapid weight gain may result in amenorrhea by altering pulsatile GnRH release.

History of excessive food intake may be due to Prader-Willi syndrome [33] or leptin deficiency, [34] both of which cause both extreme obesity and amenorrhea.

Women with hypothalamic amenorrhea have lower serum leptin concentrations, which may contribute to their low gonadotropin secretion. Leptin administration resulted in improvement of the reproductive axis in one study of women with functional hypothalamic amenorrhea. [35, 36]

Kisspeptin, a neural signal that acts directly on GnRH neurons to stimulate neuronal firing, and which may act downstream from leptin as an integrator of metabolic cues to the GnRH pulse generator, is also down regulated in cases of hypothalamic amenorrhea. Interestingly, exogenous administration of kisspeptin to women with hypothalamic amenorrhea acutely stimulates gonadotropin secretion, an effect similar to what is seen with leptin administration. [37]

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