We report herein the case of 32-year-old woman with situs inversus, thrombophilia, antiphospholipid syndrome and severe premenstrual syndrome (PMS) with cerebral edema and epileptic seizures prior to menstruation. Seven days prior to regular menstruation she developed severe PMS, including headache, blurred vision, epileptic seizures, urinary incontinence, craving for food, depression and irritability. Papilledema was detected. Daily hormone analyses prior to and during menstruation confirmed an ovulatory cycle with extremely high progesterone, prolactin and insulin levels in the late luteal phase. From day 29 to day 31, progesterone and insulin decreased sharply and the estradiol/progesterone ratio changed, leading to epileptic seizures and the peak of her symptoms. Diuretic treatment was administered. All symptoms disappeared during the first few days of menstruation. A novel oral contraceptive, containing ethinyl estradiol and drospirenone, an antimineralocorticoid progestogen, was given during the next cycle and hormone analyses were repeated. All symptoms were reduced significantly and no cerebral edema and epileptic seizures occurred. This is the first report of a woman with severe PMS and cerebral edema being treated successfully with an oral contraceptive containing drospirenone.