The neuroendocrinology of amenorrhea.

Hypothalamic amenorrhea has a pathophysiologic basis. Loss of gonadotropin-releasing-hormone (GnRH) pulse amplitude and frequency is the proximal event in the evolution of hypogonadotropic hypogonadal amenorrhea. Except for rare conditions in which the parenchymal source of GnRH is destroyed, the major cause of dysfunction in GnRH is thought to be related to abnormalities of the neurotransmitters that control GnRH synthesis, storage and timely discharge. The dopamine/norepinephrine and endorphin systems are the principal targets of current research. This new knowledge should have a major impact on physicians' thinking about hypothalamic amenorrhea. A spectrum of clinically recognizable disorders appears in conjunction with alterations in GnRH secretions. Temperature control, appetite, fluid volume and behavioral distortions are now understandable as expressions of expanding hypothalamic dysfunction.