Menstrual migraine represent a big challenge for practitioners. Various therapy try to alleviate these attacks, usually long half-life triptans and-or anti-inflammatory drugs, combined with caffeine, magnesium etc, but sometimes without efficacy. To support this limited class of patients, we considered to use the Oxycodone/Naloxone Extended Release (O/N-ER) for its favourable mechanism of action on neuropathic pain, long half life and well documented gastrointestinal safety. Recruitment is only for patients non-responders to classical preventive therapy. We have collected 33 patients, 25 with pure menstrual migraine, 8 with menstrual correlated migraine, reduction of days with migraine was significant passing from 3,5 to 2 day per attack,with also a significant reduction in pain at NRS scale from 7,7 with classical preventive therapy to 4,1 with O/N-ER, with also high level of tollerability.