Is calcitonin gene-related peptide a modulator of menopausal vasomotor symptoms?

Abstract

Calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed in the central and peripheral nervous systems, which is known as a potent vasodilator. Postmenopausal women who experience hot flushes have high levels of plasma CGRP, suggesting its involvement in menopausal vasomotor symptoms. In this review, we describe the biochemical aspects of CGRP and its effects associated with deficiencies of sexual hormones on skin temperature, vasodilatation, and sweating as well as the possible peripheral and central mechanisms involved in these events. Several studies have shown that the effects of CGRP on increasing skin temperature and inducing vasodilatation are potentiated by a deficiency of sex hormones, a common condition of postmenopausal women. Additionally, the medial preoptic area of the hypothalamus, involved in thermoregulation, contains over 25-fold more CGRP-immunoreactive cells in female rodents compared with male rodents, reinforcing the role of female sex hormones on the action of CGRP. Some studies suggest that ovarian hormone deficiency decreases circulating endogenous CGRP, inducing an upregulation of CGRP receptors. Consequently, the high CGRP receptor density, especially in blood vessels, amplifies the stimulatory effects of this neuropeptide to raise skin temperature in postmenopausal women during hot flushes. The duration of the perception of each hot flush in a woman is brief, while local reddening after intradermal administration of α-CGRP persists for 1 to 6 h. This contrast remains unclear.