Reversible Cerebral Vasoconstriction Syndrome after starting Medroxyprogesterone Acetate Therapy for Heavy Menstrual Bleeding, A Case Report

Reversible Cerebral Vasoconstriction Syndrome after starting Medroxyprogesterone Acetate Therapy for Heavy Menstrual Bleeding, A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reversible Cerebral Vasoconstriction Syndrome after starting Medroxyprogesterone Acetate Therapy for Heavy Menstrual Bleeding, A Case Report Shawn Zhi Zheng Lin, Marco Lizwan, Sumit Kumar Sonu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3880312/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Introduction: We highlight an unusual side effect of medroxyprogesterone acetate (MPA) directly attributed to Reversible cerebral vasoconstriction syndrome (RCVS) in a young patient. Case Presentation: We describe the case of a 36-year-old lady with a significant history of heavy menstrual bleeding (HMB) secondary to adenomyosis presenting with new onset migranous headaches and right upper limb weakness after being started on MPA treatment two months prior. Magnetic Resonance Imaging (MRI) of the brain revealed acute infarcts in the left frontal lobe and right parieto-occipital region while Magnetic Resonance Angiography (MRA) demonstrated widespread luminal irregularities throughout the anterior and posterior circulations. After stopping the MPA, her headaches and weakness resolved and a repeat MRA two months later showed resolution of the multi-focal intracranial stenoses. The patient was diagnosed with RCVS secondary to MPA given the onset of headaches and strokes with multi-focal intracranial stenoses shortly after initiation of MPA and resolution of the clinical and radiological abnormalities after the drug was stopped. Conclusion To the best of our knowledge, this is the first case of RCVS that has been directly attributed to the use of MPA. Although the exact pathophysiology of RCVS has yet to be determined, this case might contribute to the understanding of its underlying mechanisms. Reversible cerebral vasoconstriction syndrome medroxyprogesterone acetate young stroke case report Figures Figure 1 Introduction RCVS refers to a complex neurovascular syndrome characterized by multifocal reversible vasoconstriction of cerebral arteries with clinical manifestation of multiple abrupt thunderclap headaches 1 . It comprises of various previously known entities such as Call-Fleming syndrome, postpartum angiopathy, migraine angiitis or drug-induced cerebral angiopathy, depending on the specialist that patients presented to, such as the Neurologist, rheumatologist, or Obstetrician. RCVS has the highest incidence rate in the mid-40s and has female predilection 2 . The pathophysiology of RCVS remains elusive with multiple triggers from the post-partum state to the use of vasoactive substances being reported as possible precipitating factors 3 . Here we present a young woman with HMB in whom RCVS developed following MPA therapy. Case Presentation A 36-year-old female presented with a one-day history of acute right upper limb weakness on a background of severe new-onset headaches which started two months ago, associated with photophobia and phonophobia. On neurological examination, there was mild weakness in right fingers flexion and adduction as well as mild dysmetria on the right. Her past medical history was significant for HMB secondary to adenomyosis that was recently started on MPA treatment two months prior, approximately a week before the onset of her headaches. She does not have any personal or family history of migraine, young stroke and has no known cardiovascular risk factors. Initial Computed Tomography (CT) of the brain was unremarkable but subsequent MRI of the brain detected acute infarcts in left frontal and right parietal occipital regions (Fig. 1A and B). MRA of the brain demonstrated widespread luminal irregularities with at least moderate stenoses of the bilateral anterior, middle, and posterior cerebral arteries with more severe involvement of the proximal and mid-portion of the arteries and relative preservation of the more distal branches (Fig. 1C). Magnetic Resonance Venography (MRV) did not find any evidence of venous sinus thrombosis. Carotid and vertebral duplex ultrasound did not detect any stenoses or plaques over the extracranial carotid and vertebral arteries. Her fasting lipids, fasting glucose and HbA1c were within normal limits, and she was normotensive. A 24-hour Holter and Transthoracic Echocardiogram were unremarkable. A HIV screen was negative, and her serum homocysteine level was within normal limits. An autoimmune screen revealed a normal Erythrocyte Sedimentation Rate with only mildly elevated Anti-Double Stranded DNA while the Extractable Nuclear Antigen Antibodies profile, Anti-Nuclear Antibodies profile, Anti-Cardiolipin IgM and IgG, Lupus Anticoagulant, Beta-2 Glycoprotein IgM and IgG, Anti-Myeloperoxidase Antibody, Anti-Proteinase-3 antibodies, Protein S, Protein C were within normal limits. A specialist rheumatology consult found no clinical features of Systemic Lupus Erythematosus or other connective tissue diseases and there were no other signs of systemic vasculitis. Cerebral Spinal Fluid (CSF) studies were unremarkable. There was no pleocytosis, raised protein or opening pressure nor reduced CSF/serum glucose ratio. CSF lactate was not raised. Meningitis viral and bacterial multiplex, CSF Gram stain and bacterial culture were negative as were CSF Venereal Disease Research Laboratory (VDRL), Acid-Fast Bacilli, Cryptococcus Antigen and Fungal studies. Cytology and Flow Cytometry were unremarkable for any malignant cells or clonal B cells. She was started on aspirin in view of the new infarcts and her MPA stopped as her HMB had improved. Prior to discharge the power over her right hand had started to improve. On serial follow-up clinic visits, the patient reported that her headaches and weakness had completely resolved, and her neurological examination was normal. Repeat MRI and MRA of the brain two months later showed complete resolution of the previous stenoses (Fig. 1D) with no new infarcts detected. The patient was diagnosed with Reversible cerebral vasoconstriction syndrome (RCVS) secondary to MPA given the onset of headaches and strokes with multi-focal intracranial stenoses shortly after initiation of the drug and resolution of the clinical and radiological abnormalities after the drug was stopped. Discussion RCVS is a complex neurovascular syndrome characterized by multifocal reversible vasoconstriction of cerebral arteries. Its clinical presentation often starts acutely with thunderclap headaches which recur in approximately 85–90% of patients, usually triggered by exertion or the Valsalva manoeuvre, but can also present with migraine-like symptoms as in our patient 1 . Up to 70% of patients go on to develop convexity subarachnoid haemorrhages, parenchymal haemorrhages, ischemic strokes or vasogenic brain oedema 4 . RCVS has the highest incidence rate in the mid-40s and has female predilection 2 . The pathophysiology of RCVS remains elusive with multiple triggers from the post-partum state to the use of vasoactive substances being reported as possible precipitating factors 3 . Endothelial dysfunction, endothelin 1, serotonin, cytokines, Vascular Endothelial Growth Factor (VEGF), enhanced oxidative stress, genetic polymorphisms, circulating micro-RNAs, and autonomic dysregulation have all been implicated as possible mechanisms. Oestrogen and progesterone mediated signalling pathways have been shown to play a significant role in influencing cerebral vascular tone and the permeability of the blood-brain barrier 5 . MPA is a synthetic form of progesterone and has a wide variety of uses including as a contraceptive and in our patient’s case, for HMB. Possible mechanisms on how progesterone causes RCVS include lowering oestrogen secretion which in turn increases endothelin 1 and systemic oxidative stress while reducing endothelial nitric oxide (NO) synthase expression and NO production 6 . When malfunctioning autoregulation and disruptions in the blood-brain barrier intensify, and the body’s innate protective mechanisms prove ineffective, it can result in the development of headaches and vasoconstrictions, giving rise to RCVS 7 . Conclusion To the best of our knowledge, this is the first case of RCVS that has been directly attributed to the use of MPA. Although the exact pathophysiology of RCVS has yet to be determined, this case might contribute to the understanding of its underlying mechanisms. Our case elegantly illustrates how the clinical history, examination findings, and ancillary investigations remain important components of the diagnostic processes and helps in identifying novel triggers for uncommon conditions such as RCVS. Abbreviations HMB (heavy menstrual bleeding), MPA (medroxyprogesterone acetate), RCVS (reversible cerebral vasoconstriction syndrome), Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography (MRA), Magnetic Resonance Venography (MRV), Computed Tomography (CT), Cerebral Spinal Fluid (CSF), Venereal Disease Research Laboratory (VDRL), Vascular Endothelial Growth Factor (VEGF), nitric oxide (NO) Declarations 1. Funding: This research did not receive any grant from any funding agency. 2. Conflicts of interest/Competing interests: The authors declare no competing interests. 3. Ethics approval: Not applicable 4. Consent to participate: Not applicable 5. Written Consent for publication: Written informed consent was obtained from the patient for publication of this case report and accompanying images. 6. Availability of data and material (data transparency): Not applicable 7. Code availability (software application or custom code): Not applicable 8. Authors' contributions: The following authors were responsible for drafting of the text, sourcing, and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: SZZL, ML. The following authors gave final approval of the manuscript: SKS. References Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012;11(10):906–17. 10.1016/s1474-4422 . (12)70135-7 [published Online First: 2012/09/22]. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology. 2002;58(1):130–3. 10.1212/wnl.58.1.130 . [published Online First: 2002/01/10]. Kaye BR, Fainstat M. Cerebral vasculitis associated with cocaine abuse. JAMA. 1987;258(15):2104–6. [published Online First: 1987/10/16]. Singhal AB. Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome as Syndromes of Cerebrovascular Dysregulation. Continuum (Minneap Minn). 2021;27(5):1301–1320. 10.1212/CON.0000000000001037 . PMID: 34618761. Krause DN, Duckles SP, Pelligrino DA. Influence of sex steroid hormones on cerebrovascular function. J Appl Physiol (1985). 2006;101(4):1252–61. Choi S, Lee JY, Bae JS, Song HK, et al. Reversible Cerebral Vasoconstriction Syndrome Associated with Levonorgestrel-Releasing Intrauterine System. Brain Sci. 2021;11(5):601. 10.3390/brainsci11050601 . PMID: 34066705; PMCID: PMC8151975. Soo Y, Singhal A, Leung T, et al. Reversible Cerebral Vasoconstriction Syndrome with Posterior Leukoencephalopathy after Oral Contraceptive Pills. Cephalalgia. 2010;30(1):42–5. 10.1111/j.1468-2982.2009.01868.x . Supplementary Files CAREchecklistRCVSCaseWriteUpSNComprehensive.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 12 Apr, 2024 Reviewers invited by journal 09 Feb, 2024 Editor assigned by journal 24 Jan, 2024 First submitted to journal 23 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3880312","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272174531,"identity":"177cf960-2074-4622-9f6a-134131765ada","order_by":0,"name":"Shawn Zhi Zheng Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYDACCTBpwcPA3sDAzNhAvBYJHgaeAyRqAaIEIrXIz25+Jl3AICFjLvk68XHhDgZ5frEDzB+/4NFicOeYmfQMoMMsZ+duNp55hsFw5uwENmkZfFokEsxu8wC1GNzO3SbN28aQYHA7gY1ZAp/DZqR/g2i5eRauhfkzPi0MN3KgttzghWthkPyAz2E3csp/8xgAtZwB+oW3TQLol8Q2aXyWAB222Zinwsbe4PjZjY9522zk+aWTD3/8gU8PxC44C+QJxgZmHoJa0AEjYVtGwSgYBaNgBAEA+e9CsmAq67oAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0006-7488-6264","institution":"National Neuroscience Institute - Singapore General Hospital Campus","correspondingAuthor":true,"prefix":"","firstName":"Shawn","middleName":"Zhi Zheng","lastName":"Lin","suffix":""},{"id":272174532,"identity":"15ed0e44-994e-4fe8-ac95-a7aed20bb091","order_by":1,"name":"Marco Lizwan","email":"","orcid":"","institution":"MOHH: Ministry of Health Holdings Pte Ltd","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Lizwan","suffix":""},{"id":272174533,"identity":"d94c4159-51d4-4ecc-8422-3f2a525fbd6d","order_by":2,"name":"Sumit Kumar Sonu","email":"","orcid":"","institution":"National Neuroscience Institute - Singapore General Hospital Campus","correspondingAuthor":false,"prefix":"","firstName":"Sumit","middleName":"Kumar","lastName":"Sonu","suffix":""}],"badges":[],"createdAt":"2024-01-20 01:55:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3880312/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3880312/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51084079,"identity":"dd29e1d0-7578-476b-9140-8dbd78f0ed58","added_by":"auto","created_at":"2024-02-13 19:44:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1676909,"visible":true,"origin":"","legend":"\u003cp\u003e(A) MRI Diffusion weighted imaging and (B) Corresponding ADC map of the brain demonstrating acute infarcts in the left frontal lobe and right parieto-occipital region. (C)\u003cstrong\u003e \u003c/strong\u003eMRA demonstrating widespread luminal irregularities throughout the anterior and posterior circulation with moderate to severe stenoses over the bilateral anterior cerebral arteries (white arrows), middle cerebral arteries (yellow arrows) and posterior cerebral arteries (red arrows). The proximal and mid portions of the arteries appear more severely involved with relative preservation of the more distal branches; and (D) repeat MRI and MRA of the brain done 2 months later showing resolution of the previous intracranial stenoses.\u003c/p\u003e","description":"","filename":"Fig1ABCDRCVSMPApage001.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3880312/v1/dfabc848ed2c6d4cd53b0254.jpg"},{"id":51084081,"identity":"b8724b8d-796c-4c93-9d3f-13c400e19323","added_by":"auto","created_at":"2024-02-13 19:44:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":271772,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3880312/v1/16ce8f2c-3253-4000-b8c9-cd72b3980b6a.pdf"},{"id":51084080,"identity":"bb9e054f-d748-4100-aabf-24d44ad50b09","added_by":"auto","created_at":"2024-02-13 19:44:48","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":727956,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistRCVSCaseWriteUpSNComprehensive.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3880312/v1/11ad9049130672f9c3fae1af.pdf"}],"financialInterests":"","formattedTitle":"Reversible Cerebral Vasoconstriction Syndrome after starting Medroxyprogesterone Acetate Therapy for Heavy Menstrual Bleeding, A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRCVS refers to a complex neurovascular syndrome characterized by multifocal reversible vasoconstriction of cerebral arteries with clinical manifestation of multiple abrupt thunderclap headaches\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. It comprises of various previously known entities such as Call-Fleming syndrome, postpartum angiopathy, migraine angiitis or drug-induced cerebral angiopathy, depending on the specialist that patients presented to, such as the Neurologist, rheumatologist, or Obstetrician. RCVS has the highest incidence rate in the mid-40s and has female predilection\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The pathophysiology of RCVS remains elusive with multiple triggers from the post-partum state to the use of vasoactive substances being reported as possible precipitating factors\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Here we present a young woman with HMB in whom RCVS developed following MPA therapy.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 36-year-old female presented with a one-day history of acute right upper limb weakness on a background of severe new-onset headaches which started two months ago, associated with photophobia and phonophobia. On neurological examination, there was mild weakness in right fingers flexion and adduction as well as mild dysmetria on the right.\u003c/p\u003e\u003cp\u003eHer past medical history was significant for HMB secondary to adenomyosis that was recently started on MPA treatment two months prior, approximately a week before the onset of her headaches. She does not have any personal or family history of migraine, young stroke and has no known cardiovascular risk factors.\u003c/p\u003e\u003cp\u003eInitial Computed Tomography (CT) of the brain was unremarkable but subsequent MRI of the brain detected acute infarcts in left frontal and right parietal occipital regions (Fig.\u0026nbsp;1A and B). MRA of the brain demonstrated widespread luminal irregularities with at least moderate stenoses of the bilateral anterior, middle, and posterior cerebral arteries with more severe involvement of the proximal and mid-portion of the arteries and relative preservation of the more distal branches (Fig.\u0026nbsp;1C). Magnetic Resonance Venography (MRV) did not find any evidence of venous sinus thrombosis. Carotid and vertebral duplex ultrasound did not detect any stenoses or plaques over the extracranial carotid and vertebral arteries.\u003c/p\u003e\u003cp\u003eHer fasting lipids, fasting glucose and HbA1c were within normal limits, and she was normotensive. A 24-hour Holter and Transthoracic Echocardiogram were unremarkable.\u003c/p\u003e\u003cp\u003eA HIV screen was negative, and her serum homocysteine level was within normal limits.\u003c/p\u003e\u003cp\u003eAn autoimmune screen revealed a normal Erythrocyte Sedimentation Rate with only mildly elevated Anti-Double Stranded DNA while the Extractable Nuclear Antigen Antibodies profile, Anti-Nuclear Antibodies profile, Anti-Cardiolipin IgM and IgG, Lupus Anticoagulant, Beta-2 Glycoprotein IgM and IgG, Anti-Myeloperoxidase Antibody, Anti-Proteinase-3 antibodies, Protein S, Protein C were within normal limits. A specialist rheumatology consult found no clinical features of Systemic Lupus Erythematosus or other connective tissue diseases and there were no other signs of systemic vasculitis.\u003c/p\u003e\u003cp\u003eCerebral Spinal Fluid (CSF) studies were unremarkable. There was no pleocytosis, raised protein or opening pressure nor reduced CSF/serum glucose ratio. CSF lactate was not raised. Meningitis viral and bacterial multiplex, CSF Gram stain and bacterial culture were negative as were CSF Venereal Disease Research Laboratory (VDRL), Acid-Fast Bacilli, Cryptococcus Antigen and Fungal studies. Cytology and Flow Cytometry were unremarkable for any malignant cells or clonal B cells.\u003c/p\u003e\u003cp\u003eShe was started on aspirin in view of the new infarcts and her MPA stopped as her HMB had improved. Prior to discharge the power over her right hand had started to improve.\u003c/p\u003e\u003cp\u003eOn serial follow-up clinic visits, the patient reported that her headaches and weakness had completely resolved, and her neurological examination was normal. Repeat MRI and MRA of the brain two months later showed complete resolution of the previous stenoses (Fig.\u0026nbsp;1D) with no new infarcts detected.\u003c/p\u003e\u003cp\u003eThe patient was diagnosed with Reversible cerebral vasoconstriction syndrome (RCVS) secondary to MPA given the onset of headaches and strokes with multi-focal intracranial stenoses shortly after initiation of the drug and resolution of the clinical and radiological abnormalities after the drug was stopped.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRCVS is a complex neurovascular syndrome characterized by multifocal reversible vasoconstriction of cerebral arteries. Its clinical presentation often starts acutely with thunderclap headaches which recur in approximately 85–90% of patients, usually triggered by exertion or the Valsalva manoeuvre, but can also present with migraine-like symptoms as in our patient\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Up to 70% of patients go on to develop convexity subarachnoid haemorrhages, parenchymal haemorrhages, ischemic strokes or vasogenic brain oedema\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. RCVS has the highest incidence rate in the mid-40s and has female predilection\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe pathophysiology of RCVS remains elusive with multiple triggers from the post-partum state to the use of vasoactive substances being reported as possible precipitating factors\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Endothelial dysfunction, endothelin 1, serotonin, cytokines, Vascular Endothelial Growth Factor (VEGF), enhanced oxidative stress, genetic polymorphisms, circulating micro-RNAs, and autonomic dysregulation have all been implicated as possible mechanisms. Oestrogen and progesterone mediated signalling pathways have been shown to play a significant role in influencing cerebral vascular tone and the permeability of the blood-brain barrier\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eMPA is a synthetic form of progesterone and has a wide variety of uses including as a contraceptive and in our patient’s case, for HMB. Possible mechanisms on how progesterone causes RCVS include lowering oestrogen secretion which in turn increases endothelin 1 and systemic oxidative stress while reducing endothelial nitric oxide (NO) synthase expression and NO production\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. When malfunctioning autoregulation and disruptions in the blood-brain barrier intensify, and the body’s innate protective mechanisms prove ineffective, it can result in the development of headaches and vasoconstrictions, giving rise to RCVS\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo the best of our knowledge, this is the first case of RCVS that has been directly attributed to the use of MPA. Although the exact pathophysiology of RCVS has yet to be determined, this case might contribute to the understanding of its underlying mechanisms. Our case elegantly illustrates how the clinical history, examination findings, and ancillary investigations remain important components of the diagnostic processes and helps in identifying novel triggers for uncommon conditions such as RCVS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHMB (heavy menstrual bleeding), MPA (medroxyprogesterone acetate), RCVS (reversible cerebral vasoconstriction syndrome), Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography (MRA), Magnetic Resonance Venography (MRV), Computed Tomography (CT), Cerebral Spinal Fluid (CSF), Venereal Disease Research Laboratory (VDRL), Vascular Endothelial Growth Factor (VEGF), nitric oxide (NO)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e1. Funding: This research did not receive any grant from any funding agency.\u003c/p\u003e\n\u003cp\u003e2. Conflicts of interest/Competing interests: The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e3. Ethics approval: Not applicable\u003c/p\u003e\n\u003cp\u003e4. Consent to participate: Not applicable\u003c/p\u003e\n\u003cp\u003e5. Written Consent for publication: Written informed consent was obtained from the patient for publication of this case report and accompanying images.\u003c/p\u003e\n\u003cp\u003e6. Availability of data and material (data transparency): Not applicable\u003c/p\u003e\n\u003cp\u003e7. Code availability (software application or custom code): Not applicable\u003c/p\u003e\n\u003cp\u003e8. Authors\u0026apos; contributions: The following authors were responsible for drafting of the text, sourcing, and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: SZZL, ML. The following authors gave final approval of the manuscript: SKS.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDucros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012;11(10):906\u0026ndash;17. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1474-4422\u003c/span\u003e\u003cspan address=\"10.1016/s1474-4422\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (12)70135-7 [published Online First: 2012/09/22].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinghal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology. 2002;58(1):130\u0026ndash;3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.58.1.130\u003c/span\u003e\u003cspan address=\"10.1212/wnl.58.1.130\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. [published Online First: 2002/01/10].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaye BR, Fainstat M. Cerebral vasculitis associated with cocaine abuse. JAMA. 1987;258(15):2104\u0026ndash;6. [published Online First: 1987/10/16].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinghal AB. Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome as Syndromes of Cerebrovascular Dysregulation. Continuum (Minneap Minn). 2021;27(5):1301\u0026ndash;1320. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/CON.0000000000001037\u003c/span\u003e\u003cspan address=\"10.1212/CON.0000000000001037\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 34618761.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrause DN, Duckles SP, Pelligrino DA. Influence of sex steroid hormones on cerebrovascular function. J Appl Physiol (1985). 2006;101(4):1252\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi S, Lee JY, Bae JS, Song HK, et al. 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Cephalalgia. 2010;30(1):42\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1468-2982.2009.01868.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1468-2982.2009.01868.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Reversible cerebral vasoconstriction syndrome, medroxyprogesterone acetate, young stroke, case report","lastPublishedDoi":"10.21203/rs.3.rs-3880312/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3880312/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eWe highlight an unusual side effect of medroxyprogesterone acetate (MPA) directly attributed to Reversible cerebral vasoconstriction syndrome (RCVS) in a young patient.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe describe the case of a 36-year-old lady with a significant history of heavy menstrual bleeding (HMB) secondary to adenomyosis presenting with new onset migranous headaches and right upper limb weakness after being started on MPA treatment two months prior. Magnetic Resonance Imaging (MRI) of the brain revealed acute infarcts in the left frontal lobe and right parieto-occipital region while Magnetic Resonance Angiography (MRA) demonstrated widespread luminal irregularities throughout the anterior and posterior circulations. After stopping the MPA, her headaches and weakness resolved and a repeat MRA two months later showed resolution of the multi-focal intracranial stenoses. The patient was diagnosed with RCVS secondary to MPA given the onset of headaches and strokes with multi-focal intracranial stenoses shortly after initiation of MPA and resolution of the clinical and radiological abnormalities after the drug was stopped.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTo the best of our knowledge, this is the first case of RCVS that has been directly attributed to the use of MPA. Although the exact pathophysiology of RCVS has yet to be determined, this case might contribute to the understanding of its underlying mechanisms.\u003c/p\u003e","manuscriptTitle":"Reversible Cerebral Vasoconstriction Syndrome after starting Medroxyprogesterone Acetate Therapy for Heavy Menstrual Bleeding, A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-13 19:44:43","doi":"10.21203/rs.3.rs-3880312/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-04-12T10:56:11+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-09T13:53:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-24T09:09:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2024-01-23T19:04:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"32fabe32-e5e3-44f1-863e-e7c7135937cc","owner":[],"postedDate":"February 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-03T04:26:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-13 19:44:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3880312","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3880312","identity":"rs-3880312","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}