Prostanoids and catecholamines after oral administration of natural progesterone

Natural exogenous progesterone has been shown to affect the functioning of the central nervous system in man, inducing dizziness and sedation by unknown mechanisms. Seven postclimacteric women known to suffer from dizziness during natural progesterone therapy were treated with a single oral dose of 200 mg of natural progesterone on 2 occasions, with and without preceding administration of indomethacin. Cardiovascular responses, vasoactive prostanoids and catecholamines in the blood, and excretion of prostanoids in the urine were measured. Serum progesterone concentrations increased in each subject, and all the women experienced dizziness or tiredness after progesterone intake. Blood pressure and heart rate did not change. Urine excretion of immunoreactive prostaglandin E2 and 6-keto-prostaglandin1 alpha decreased significantly in the experiment without pretreatment with indomethacin, whereas indomethacin pretreatment reduced the basal excretion of prostanoids and abolished the progesterone-induced decrease in their excretion. The plasma concentrations of prostanoids and catecholamines did not change. The results confirm that natural progesterone can cause dizziness and tiredness in man. The appearance of these symptoms is not related to peripheral vasodilation or to changes in plasma prostanoid or catecholamine levels. Neither are the symptoms related to the alteration in the urinary excretion of prostanoids, since the women still suffered from tiredness and dizziness after pretreatment with indomethacin.