Physiology and treatment of hot flushes.

Abstract

Objective measures of vasomotor flushes have clarified their biologic basis and have established the peripheral reactions as compensatory mechanisms for hypothalamic thermoregulatory instability. Subsequently, investigations into the pathogenesis of flushes pointed to increasingly higher levels of control. The observed relationship between estrogen deprivation and vasomotor instability led to the hypothesis of a cause-effect relationship with LH and FSH. However, patients with pituitary insufficiency were found to have hot flushes despite a lack of LH and FSH secretion. Hypothalamic secretion of gonadotropin-releasing hormone (GnRH) was studied for possible correlation with vasomotor episodes. Patients with and without symptoms had similar levels of LH secretion, but those who had symptoms and were closer to menopause had higher peripheral levels of immunoreactive GnRH, implying involvement of a hypothalamic mechanism, although not a cause-effect relationship. With prolonged estrogen deficiency, immunoreactive GnRH levels decline. Vasomotor episodes occur after estrogen withdrawal in subgroups of patients without appreciable secretion of GnRH, although LH and FSH secretions remain elevated. Vasomotor flushes are treated most effectively with estrogen. Agents such as medroxyprogesterone acetate and lofexidine may reduce the incidence of flushes.