The effects exerted by ovarian steroids on the modulation of opioid activity were investigated in post-menopausal migraine sufferers and in healthy controls. In order to evaluate central opioid tonus, plasma LH rise after naloxone injection was measured, bearing in mind the tonic inhibition of endogenous opioid on hypothalamic LH-RH. There was no response of plasma LH to naloxone in post-menopausal women or in patients submitted to ovariectomy in fertile life. When the subjects underwent a sequential estrogens + progestagens therapy, such a response was noted from the first month of treatment; progestagens alone were ineffective. The same phenomena were also evident in post-menopausal migraine sufferers. These data indicate that ovarian steroids modulate the activity of opiate receptors in both healthy women and migraine sufferers. Interestingly, replacement therapies through ovarian steroids restored the activity of central opioid tonus in patients affected by migraine.

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