Stroke and Etonogestrel/Ethinyl Estradiol Ring (NuvaRing): Clinical, Radiological, and Prognostic Features.

BACKGROUND: A recent study found that NuvaRing (a vaginal contraceptive ring containing 15 µg ethinyl estradiol and 120 µg etonogestrel) has 2.5 times increased relative risk of thrombotic stroke compared to nonuse. OBJECTIVE: We studied a case series of 19 such patients as well as prior published case reports to clarify clinical, radiological, and prognostic features. METHODS: Medical records and imaging for 18 cases were initially systematically reviewed for consultation in a class action lawsuit. One case was seen personally outside of litigation. All 19 cases were entered into a database detailing clinical, radiological, and prognostic features as well as other potential risk factors. A literature search identified 8 additional cases. RESULTS: Average age at stroke was 31.7 ± 9.8 years; average duration of NuvaRing use prior to stroke was 11.2 months. Arterial stroke occurred in 10 of 19 (52%); 1 of 10 (10%) was hemorrhagic. Venous sinus thrombosis was present in 11 of 19 (58%) on initial imaging; 6 of 11 (54%) were hemorrhagic. The most common presenting symptom was headache (7 of 19 [37%]) and motor weakness (7 of 19 [37%]). A hypercoagulable condition was present in 3 of 19 (16%); 3 of 19 (16%) had history of hypercoagulable disease in a first-degree relative. Mortality was .5%; 8 of 19 (42%) fully recovered and 3 of 19 (15%) were discharged to rehabilitation. CONCLUSIONS: In this largest case series of NuvaRing-associated stroke to date, approximately half of the strokes are venous and half are arterial. Stroke typically occurred within the first year of use, and as soon as 2 weeks after NuvaRing initiation.

Intracerebral hemorrhage associated with oral phenylephrine use: a case report and review of the literature.

BACKGROUND: Prior reports have linked both ischemic and hemorrhagic stroke to use of sympathomimetic drugs including phenylephrine. The purpose of this study is to describe the first case, to our knowledge of intracerebral hemorrhage (ICH) after oral use of phenylephrine and to systematically review the literature on phenylephrine and acute stroke. METHODS: A case report and review of the literature. RESULTS: A 59-year-old female presented with thunderclap headache, right hemiparesis, aphasia, and left gaze deviation. Head computed tomography (CT) showed a left frontal ICH with intraventricular and subarachnoid extension. She had no significant past medical history. For the previous 30 days, the patient was taking multiple common cold remedies containing phenylephrine to treat sinusitis. CT and magnetic resonance angiography showed no causative vascular abnormality. Catheter cerebral angiography supported reversible cerebral vasoconstriction syndrome (RCVS). Phenylephrine was determined to be the most likely etiology for her hemorrhage. A review of the literature, found 7 cases describing phenylephrine use with acute stroke occurrence: female, 5 of 7 (71%); route of administration, nasal (n = 3), ophthalmic (n = 2), intravenous (n = 1), intracorporeal injection (n = 1). Stroke types were subarachnoid hemorrhage (n = 5), ICH (n = 4), and ischemic (n = 1). One case reported RCVS after phenylephrine use. CONCLUSIONS: It is scientifically plausible that phenylephrine may cause strokes, consistent with the pharmacologic properties and adverse event profiles of similar amphetamine-like sympathomimetics. As RCVS has been well described in association with over-the-counter sympathomimetics, a likely, although not definitive, causal relationship between phenylephrine and ICH is proposed.