Hepatic dysfunction in development of menopausal hot flushes?

Obese menopausal women tend to suffer more frequently and more severely from hot flushes, though they have higher residual estrogen levels due to the conversion of adrenal androgens in fat tissue. Phytoestrogens, while not exhibiting clinically relevant estrogenic effects on peripheral reproductive tissues, seem to alleviate hot flushes in doses attainable with dietary supplementation. This paper aims to address these controversies. A synergistic action of obesity and estrogens may cause hepatic dysfunction involving inflammatory Kupffer cell activation and generation of pyrogenic signals that reach the thermoregulatory centers via the vagal route. Sudden withdrawal of this perpetual pyrogenic impetus at the onset of menopause results in a thermoregulatory imbalance. The occasional downward sliding of the thermoregulatory setpoint serves to trigger the hot flush event. Repercussions of this theory involve a possible resolution for the paradox of why estrogen-sensitive cancers manifest more frequently at the age when endogenous estrogen levels decline.