Norethisterone induced cerebral venous sinus thrombosis (CVST): a rare case report and review of literature

Ramya T, Prakash B, Devi B


The association between the progestin only pill used for treatment of menstrual disorders and cerebral venous sinus thrombosis (CVST) has rarely been reported in the literature. This report describes a case of cerebral venous thrombosis following intake of norethisterone for menorrhagia secondary to polycystic ovary syndrome in a young woman with undiagnosed underlying hyperhomocysteinemia. A 24 year old married woman presented with acute onset of headache, vomiting and right focal seizures. MRI Cerebral venogram and CT Brain revealed thrombosed anterosuperior segment of superior sagittal sinus and haemorrhagic infarct in right frontoparietal region. The risk factors were acquired hyperhomocysteinemia, polycystic ovary syndrome and norethisterone for menorrhagia. The patient was treated with low molecular weight heparin, followed by warfarin, vitamin B12, vitamin B6 and folic acid. She made a total recovery. Although venous thrombosis is usually linked to the ingestion of estrogen, rather than  progestogen, this case illustrates that patients who are prescribed progestogen only pills for  gynaecological disorders may develop thrombosis, especially if they have predisposing metabolic  disorders.


Cerebral venous sinus thrombosis, Norethisterone, Polycystic ovary syndrome, Hyperhomocysteinemia

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Denise M. Lemke, Lofti Hacein-Bey. Cerebral Venous Sinus Thrombosis. J Neurosci Nurs. 2005;37(5):258-64.

Van Gijn J. Cerebral venous thrombosis: Pathogenesis, presentation and prognosis. J R Soc Med. 2002;93:230-3.

Baumgartner RW, Studer A, Arnold M. Recanalisation of cerebral venous thrombosis. J Neurolneurosurg Psychiatry. 2003;74:459-61.

Jordan W. Pulmonary embolism. Lancet. 1961;278:1146-7.

Oral contraception and thrombo-embolic disease. J R Coll Gen Pract. 1967;13:267-79..

Inman WH, Vessey MP. Investigation of deaths from pulmonary, coronary, and cerebral thrombosis and embolism in women of child-bearing age. BMJ. 1968;2:193-9.

Sartwell PE, Masi AT, Arthes FG et al. Thromboembolism and oral contraceptives: an epidemiologic case-control study. Am J Epidemiol. 1969;90:365-80.

Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. BMJ. 1969;2:651-7.

Naess IA, Christiansen SC, Romundstad P et al. J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007;5:692-9.

Thorogood M, Villard-Mackintosh L. Combined oral contraceptives: risks and benefits. Br Med Bull. 1993;49:124-39.

Wharton C, Blackburn R. Lower dose pills. Population Rep. 1988;16:1-31.

Stolley PD, Tonascia JA, Tockman MS et al. Thrombosis with low-estrogen oral contraceptives. Am J Epidemiol. 1975;102:197-208.

World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. Lancet. 1995;346:1575-82.

Inman WH, Vessey MP, Westerholm B et al. Thromboembolic disease and the steroidal content of oral contraceptives. A report to the Committee on Safety of Drugs. BMJ. 1970;2:203-9.

Vessey M, Mant D, Smith A et al. Oral contraceptives and venous thromboembolism: findings in a large prospective study. Br Med J. (Clin Res Ed). 1986;292:526.

Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception. 2002;65:187-96.

Meade TW, Greenberg G, Thompson SG. Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50- and 30-microgram oestrogen preparations. BMJ. 1980;280:1157-61.

Kemmeren JM, Algra A, Meijers JC et al. Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation. Thromb Haemost. 2002;87:199-205.

Kemmeren JM, Algra A, Meijers JC, et al. Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial. Blood. 2004;103:927-33.

Van Hylckama Vlieg, A, Helmerhorst FM, Rosendaal FR. The risk of deep venous thrombosis associated with injectable depot-medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol. 2010;30:2297-300.

Kottke-Marchant K, R Green, D Jacobsen et al. High plasma homocysteine: a risk factor for arterial and venous thrombosis in patients with normal coagulation profiles. Clini appl Thromb hemost. 1997;3:239-44.

Falcon C, M Cattanco, D panzer et al. High prevalence of hyperhomocysteinemia with juvenile venous thrombosis. Arterioscler thromb. 1994;14:1080-3.

Bauer KA. Hypercoagulable states. In: Hoffman R, Benz EJ Jr, Shattil SJ et al. eds. Hematology: Basic Principles and Practice. 3rd ed. New York: Churchill Livingstone; 1995: 1781-1795.

Allaart CF, Briet E. Familial venous thrombophilia. In: Bloom AL, Forbes CD, Thomas DP et al. eds. Haemostasis and Thrombosis. 3rd ed. London: Churchill Livingstone; 1994: 1349.

Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med. 1994;330:517-22.

Koster T, Rosendaal FR, de Ronde H et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 1993;342:1503-6.

Griffin JH, Evatt B, Wideman C et al. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood. 1993;82:1989-93.

Harris JM, Abramson N. Evaluation of recurrent thrombosis and hypercoagulability. Am Fam Physician. 1997;56:1591-6,1601.

Gandrille S, Greengard JS, Alhenc-Gelas M, et al. Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM. Blood. 1995;86:219-24.

Gatt A, Makris M. Hyperhomocysteinemia and venous thrombosis. Semin Hematol. 2007 Apr;44(2):70-6.

Hitendra Singh Tanwar, AK Gadpayle. A rare case of drug induced cortical venous sinus thrombosis presenting as subarachnoid haemorrhage in a patient of menorrhagia: A great dilemma in management. JIACM. 2010;11(4):330-5.

Rajput R, Dhuan J, Agarwal S. CVST in a young woman taking norethindrone acetate for DUB: a case report and review of literature. J Obstet Gynaecol Can. 2008 Aug;30(8):680-3.

Hitosugi M, Kitamira O, Takatsu A. A case of dural sinus thrombosis during the medication of medroxy progesterone acetate. Nihon Hoigaku zasshi. 1997 Dec;51(6):452-6.