Norethisterone enanthate–induced cerebral sino-venous thrombosis (CSVT): A rare case report

Vijayan Sharmila; Sri S Kalluri

doi:10.4103/AMJM.AMJM_23_22

CASE REPORT

Year : 2022 | Volume : 18 | Issue : 3 | Page : 92-95

Norethisterone enanthate–induced cerebral sino-venous thrombosis (CSVT): A rare case report

Vijayan Sharmila, Sri S Kalluri
Department of Obstetrics & Gynecology, All India Institute of Medical Sciences (AIIMS), Mangalagiri, Andhra Pradesh, India

Date of Submission	26-May-2022
Date of Acceptance	23-Aug-2022
Date of Web Publication	13-Dec-2022

Correspondence Address:
Dr. Vijayan Sharmila
Department of Obstetrics & Gynecology, All India Institute of Medical Sciences (AIIMS), Mangalagiri 522 503, Andhra Pradesh
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AMJM.AMJM_23_22

Abstract

Cerebral sino-venous thrombosis is a potential life-threatening condition that requires rapid diagnosis and urgent treatment. The association between progestin-only pill used for the treatment of menstrual disorders and cerebral venous thrombosis has rarely been reported in the literature. We report a case of cerebral venous thrombosis following the intake of norethisterone for menorrhagia in a young woman. 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 gynecological disorders may develop thrombosis.

Keywords: Abnormal uterine bleeding, cerebral sino-venous thrombosis, norethisterone

How to cite this article:
Sharmila V, Kalluri SS. Norethisterone enanthate–induced cerebral sino-venous thrombosis (CSVT): A rare case report. Amrita J Med 2022;18:92-5

How to cite this URL:
Sharmila V, Kalluri SS. Norethisterone enanthate–induced cerebral sino-venous thrombosis (CSVT): A rare case report. Amrita J Med [serial online] 2022 [cited 2023 Jun 4];18:92-5. Available from: https://ajmonline.org.in/text.asp?2022/18/3/92/363499

Introduction

Cerebral sino-venous thrombosis (CSVT) is a rare stroke-like syndrome with significant morbidity and mortality, associated with hypercoagulable condition and present with a myriad of signs and symptoms ranging from simple headache to localizing neurologic deficits, frank seizures, and coma. Prompt recognition and treatment can prevent life-threatening complications and result in complete recovery.^[1]

Case Report

A 19-year-old unmarried woman presented to the Obstetrics and Gynecology out patient department with a history of irregular menstrual cycles since menarche, attained at 12 years of age, once in 5 months with moderate flow, no clots, and no dysmenorrhea. She started to have menorrhagic cycles since 6 years, once in 3 months, bled for 5–6 days, changed 6–7 pads/day, and associated with clots and dysmenorrhea. She took over the counter T. tranexamic acid 500 mg thrice daily and Ayurvedic medication for which she had no response. A family physician had prescribed her cyclical T. norethisterone acetate 10 mg from D5 to D25 of cycles, which she continued to take for a period of 2 years. While on therapy, she developed a sudden onset of severe headache, associated with nausea and vomiting, which did not respond to analgesics and antiemetics. There was no history of fever, blurring of vision, photophobia, or gait disturbance. Her symptoms worsened over a period of 1 week and also had one episode of tonic-clonic seizures. She was not on any medications other than norethisterone prior to this episode. She was not a known case of diabetes, hypertension or metabolic syndrome, migraine, cardiac disorder, coagulation disorder, and her family history was insignificant. On general examination, the patient’s general condition is fair, vitals were stable, with body mass index (BMI) of 26 kg/m². All routine blood investigations, including complete blood count (hemoglobin %: 12 g/dL, total leukocyte count: 15,700 cells/cumm, platelets: 3,88,000 cells/cumm, neutrophils: 68, lymphocytes: 26, monocytes: 04, eosinophils: 02, basophils: 0), liver function tests, renal function tests, urinalysis, fasting lipids, and electrolytes were within normal limits. Serum prolactin level was 22.35 ng/mL. Prothrombin time, partial thromboplastin time, and international normalized ratio were 14 s, 27.2 s, and 1.6, respectively, and erythrocyte sedimentation rate was 25 mm/h. The screening for antiphospholipid antibodies and thrombophilia was negative. The ultrasonography of whole abdomen and pelvis is unremarkable, uterus: anteverted, measuring 6.9 × 3.3 × 3.9 cm, and uniform myometrial echotexture; no focal lesions, endometrial thickness is of 5 mm, right and ovaries: normal size and volume, no adnexal cysts. 2D echocardiogram was within normal limits. CT scan of the brain revealed hyperdense dural venous sinuses consistent with CSVT. No parenchymal hematoma or lesion was evident. The magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) revealed thrombosis of superior sagittal sinus, right transverse sinus, and right sigmoid sinus [Figure 1] and [Figure 2]. The blooming of signal on the gradient imaging with a loss of flow void on conventional sequences was noted in the dural venous sinuses. Radiology imaging was suggestive of CSVT, probably due to prolonged duration of drug therapy with norethisterone enanthate. The drug was immediately stopped and was treated with antiedema measures, antiepileptics, low-molecular-weight heparin, followed by oral anticoagulants. The patient recovered completely, and there were no further episodes of seizures, headache, and vomiting. Oral anticoagulant therapy was continued for up to 6 months. Her condition was stable during this period, she got cycles once in 2 months, and menorrhagia was treated with tranexamic acid and ormeloxifene. MRI with MRV done 6 months later showed complete recanalization, and no thrombosis in the superior sagittal, right transverse, and sigmoid sinuses, and no acute intracranial hemorrhages. She was prescribed ormeloxifene 30 mg twice a week for abnormal uterine bleeding, as it is nonhormonal drug and having least thrombogenic potential, and was advised to avoid all prothrombotic drugs including norethisterone enanthate for lifelong and is currently on regular follow-up.

Figure 1: MRV showing thrombosis of superior sagittal sinus

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Figure 2: MRV showing thrombosis of the right transverse sinus and right sigmoid sinus

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Discussion

CSVT is an uncommon but potentially fatal condition, especially in young women. Common etiologies include hypercoagulable states, dehydration, adjacent infectious processes, oral contraceptives, hormone replacement therapy, pregnancy, and puerperium. CSVT was found to be more common in women than men (3:1 ratio).^[1],[2] In 20%–35% of cases, a cause cannot be identified.^[2]

CSVT is an uncommon and tricky condition, which presents with unpredictable presentation and prognosis. Most of the cases present with chronic headache, associated with vomiting, which may be misdiagnosed as migraine. The presentation of CSVT in isolation, in the absence of focal neurological signs or papilledema, and with normal antiphospholipid and thrombophilia screen poses an even greater diagnostic challenge. This feature has been shown to occur in only 15% of CSVT cases.^[3],[4]

Studies have revealed that combined oral contraceptives (COCs) are associated with 2–6 fold increase in risk of venous thrombosis.^[5] Estrogen compound (ethinylestradiol) is thought to cause the increased risk of thrombosis and reducing the dose of ethinyloestradiol in COCs would result in a reduced risk of CSVT.^[6] In addition, coagulation is more pronounced in oral contraceptives containing desogestrel (a third-generation progesterone) than levonorgestrel (a second-generation progesterone), which may be explained by a less-effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.^[5] Hence, venous thrombosis is more associated with higher doses of ethinylestradiol, as well as a third-generation progesterone. Norethisterone enanthate, first-generation progesterone, has a low risk of causing CSVT when compared with third-generation progesterones. Our patient developed CSVT following a prolonged intake of cyclical norethisterone for the treatment of puberty menorrhagia.

Contrast-enhanced CT(CECT) MRI, or MRV aids in the diagnosis of CSVT. CECT shows the classic empty delta sign, produced by an intraluminal filling defect surrounded by contrast in the posterior part of the superior sagittal sinus.^[7] The angiography of brain is reserved for cases where MRI/CECT is inconclusive.^[6]

The thrombosis of cerebral veins results in cerebral edema and venous infarction. The thrombosis of the major sinuses causes impaired absorption of cerebrospinal fluid and intracranial hypertension (ICH).^[7] These lead to four possible clinical syndromes: (1) isolated ICH presents with severe headache (90%); (2) focal neurological deficits (44%) such as hemiparesis; (3) seizures (30%–40%); and (4) encephalopathy (22%).^[6] Our patient presented with progressively worsening headache and vomiting followed by an episode of seizure.

Conclusion

We report a rare case of CSVT in a young adolescent girl following the intake of norethisterone for the treatment of menorrhagia. 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 gynecological disorders may develop thrombosis. High clinical suspicion and prompt diagnosis and treatment will aid in full recovery of this life-threatening condition.

Acknowledgement

Nil.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Authorship

All authors had access to the data and a role in writing this report.

Declaration of patient consent

The authors certify that they have obtained written informed consent of the patient for publishing the case details in a journal.

References

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