Estrogen's Impact on Cognitive Functions in Multiple Sclerosis

Abstract

It has long been suspected that hormonal factors contribute directly and indirectly to the etiology and pathogenesis of multiple sclerosis (MS). The susceptibility of MS is higher in women than in men and women are even more susceptible to hormonal influences when onset occurs at an early or delayed age. Pregnancy has a short-term favorable effect on the course of the disease but there is an increased rate of relapse during the postpartum period. In addition, women often report premenstrual exacerbation of their symptoms with remission during menses. These findings suggest that in women estrogens may exert a stabilizing effect on the clinical manifestations of MS. The role of estrogens is supported also by observations of a higher incidence of cognitive impairment in women than men with MS. A 50 year old woman with a remitting progressive MS experienced profound deterioration in cognitive functions during withdrawal from estrogen therapy which was initiated for the treatment of amenorrhea. Improvement in cognitive functions occurred shortly after she restarted therapy with an estrogen/progesterone preparation and was maintained during long term therapy. Serotonin (5-HT) mechanisms have been implicated in memory functions and estrogens modulate these functions through an interaction with 5-HT₂ receptors in the cerebral cortex and limbic system. It is suggested that estrogen withdrawal induces impairment in cognitive functions through dysregulation of 5-HT₂ receptor activity and 5-HT neurotransmission. These findings suggest that estrogens have a beneficial influence on cognitive functions in MS patients and that hormonal supplementation might be advised in menopausal and postmenopausal MS patients for the prevention of cognitive deterioration.

Key Words:

• Multiple sclerosis
• estrogens
• cognitive functions
• serotonin (5-HT)
• 5-HT₂ receptors
• frontal cortex