The flush revisited

A nadir of LH precedes the onset of the flush and a flush is never seen without an LH pulse. However, after surgical and medical (GnRH agonist) hypophysectomy flushing occurs while LH is absent, thus LH itself is not the cause of the flush. GnRH agonist treatment induces low LH, whereas flushes remain, even when oestrogens are supplemented, suggesting that GnRH itself is the mediator. As flushes are preceded by a spike of LH-RH, GnRH involvement is most likely. Pulsatile administration of GnRH does not induce flushes, whereas continuous administration does. Thus it is the interference with the pulsatile pattern of GnRH that causes flushes. Even high doses of oestradiol during GnRH agonist treatment do not abolish flushes, whereas the alpha 2-adrenergic agonists such as clonidine and alpha-methyldopa abolish flushes during treatment with GnRH agonists. Thus, dysregulation of the GnRH releasing clock center in the nucleus arcuatus in the mediobasal hypothalamus is associated with altered central alpha-receptor activity which results in lowering of the set point of the central thermostat and the circulatory changes. The balance of evidence indicates that interference with the pulsatile pattern of GnRH causes the flush.