Cerebral circulation disorders in women using combined oral contraceptives

Full Text:


The study is aimed at using combined oral contraceptives (COCs) and subsequent risk of developing cerebral circulation disorders (CCD), which is posed at the fine border between gynecology, hemostasiology and neurology. We discuss risk factors for thrombotic complications occurring upon COCs administration, pathogenetic mechanisms behind CCD, a COCs impact on hemostasis system, and their relation to risk of developing diverse stroke types. Inherited and acquired thrombophilia are discussed as one of the most important factors determining elevated CCD risk related to COCs use. We provide a detailed description of most thrombogenic genetic polymorphisms such as mutated Factor V Leiden gene, prothrombin G20210А gene etc., their role in stroke development, including conditions for COCs use. Special emphasis is made on insights into inherited and acquired АDАMTS-13 deficiency as well as antiphospholipid syndrome as factors contributing to stroke in females receiving hormonal contraceptives.

About the Authors

M. D. Andreeva
Kuban State Medical University, Health Ministry of Russian Federation
Russian Federation

Margarita D. Andreeva – MD, Dr Sci Med, Professor, Associate Professor, Department of Obstetrics, Gynecology and Perinatology

Scopus Author ID: 57200068605

4 Mitrofana Sedina Str., Krasnodar 350063

M. G. Novosartyan
Kuban State Medical University, Health Ministry of Russian Federation
Russian Federation

Margarita G. Novosartyan – MD, Postgraduate Student, Department of Obstetrics, Gynecology and Perinatology

4 Mitrofana Sedina Str., Krasnodar 350063

N. V. Samburova
Sechenov University
Russian Federation

Natalia V. Samburova – MD, PhD, Associate Professor, Department of Pathophysiology, Institute of Clinical Medicine

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

I. V. Khamani
Sechenov University
Russian Federation

Inessa V. Khamani – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991


1. Arnett D.K., Blumenthal R.S., Albert M.A. et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. Circulation. 2019;140(11):е596–е646.

2. Denorme F., Kraft P., Pareyn I. et al. Reduced ADAMTS13 levels in patients with acute and chronic cerebrovascular disease. PLoS One. 2017;12(6):e0179258.

3. Karakhalis L.Yu. Personified choice of hormonal contraception. [Personificirovannyj vybor gormonal'noj kontracepcii]. Ginekologiya. 2018;20(4):52–4. (In Russ.).

4. Muminova M.S. Thromboembolic complications associated with combined opal contraceptives. [Tromboembolicheskie oslozhneniya pri primenenii kombinirovannyh oral'nyh kontraceptivov]. Alleya nauki. 2018;8(11):96–100. (In Russ.).

5. Lloyd-Jones D.M., Hong Y., Labarthe D. et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s Strategic Impact Goal through 2020 and beyond. Circulation. 2010;121(4):586–61.

6. Kuznetsova I.V., Sukhanova G.A. Contraception and risk of apterial trombosis. [Kontracepciya i risk arterial'nogo tromboza]. PMZh. Mat' i Ditya. 2013;21(23):1128–33. (In Russ.).

7. Blinov D.V., Ushakova T.I., Makatsariya N.A. et al. Hormonal confusion and magnesium deficiency: a subanalysis of the MAGYN study. [Gormonal'naya kontracepciya i deficit magniya: rezul'taty subanaliza issledovaniya MAGYN]. Akusherstvo, Ginekologia i Reprodukcia. 2017;11(1):36–48. (In Russ.).

8. Makatsariya A.D., Dadak Ch., Bitsadze V.O. et al. The results of the second wave of investigation of the profile of patients with hormone-dependent conditions and magnesium deficiency. [Rezul'taty vtoroj volny issledovaniya profilya pacientok s gormonal'no-zavisimymi sostoyaniyami i deficitom magniya]. Akusherstvo i ginekologiya. 2017;(5):124–31. (In Russ.).

9. Medical Acceptance Criteria for Methods of Contraception. 5th ed. [Medicinskie kritepii priemlemosti dlya ispol'zovaniya metodov kontracepcii. 5-e izd]. Zheneva: VOZ, 2015. 192 p. (In Russ.). Available at:

10. Karakhalis L.Yu., Papova N.S., Mayorova A.V. Treating endometriosis with hormonal contraceptives. [Lechenie genital'nogo endometrioza gormonal'nymi kontraceptivami]. Medicinskij sovet. 2016;(2):6–11. (In Russ.).

11. Karakhalis L.Yu., Fedorovich O.K. Differential use of combined oral contraceptives. [Differencirovannoe primenenie kombinirovannyh peroral'nyh kontraceptivov]. Akusherstvo i ginekologiya. 2006;(6):51–4. (In Russ.).

12. Benjamin E.J., Muntner Р., Alonso А. et al. Heart disease and stroke statistics – 2019 Update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.

13. Champaloux S.W., Tepper N.K., Monsour M. et al. Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke. Am J Obstet Gynecol. 2017;16(5):489.e1–489.e7.

14. Fraser A., Catov J.M., Lawlor D.A., Rich-Edwards J.W. Pregnancy characteristics and women’s cardiovascular health. In: Handbook of life course health development. Springer International Publishing, 2018. 145–65.

15. Proia K.K., Thota A.B., Njie G.J. et al. Team-based care and improved blood pressure control: a community guide systematic review. Am J Prev Med. 2014;47(1):86–99.

16. Baart S.J., Dam V., Scheres L.J.J., et al., CREW consortium. Cardiovascular risk prediction models for women in the general population: A systematic review. PLoS One. 2019;14:e0210329. pmid:30620772.

17. Belbasis L., Savvidou M.D., Kanu C. et al. Birth weight in relation to health and disease in later life: an umbrella review of systematic reviews and meta-analyses. BMC Med. 2016;14(1):147. pmid:27677312.

18. Carlton C., Banks M., Sundararajan S. Oral contraceptives and ischemic stroke risk. Stroke. 2018;49(4):e157–e159.

19. Kaminski P., Szpotanska-Sikorska M., Wielgos M. Cardiovascular risk and the use of oral contraceptives. Neuro Endocrinol Lett. 2013;34(7):587–9.

20. Xu X., Li J., Sheng W., Liu L. Meta-analysis of genetic studies from journals published in China of ischemic stroke in the Han Chinese population. Cerebrovasc Dis. 2008;26:48–62.

21. Li F., Zhu L., Zhang J. et al. Oral contraceptive use and increased risk of stroke: A dose-response meta-analysis of observational studies. Front Neurol. 2019;(10):993.

22. Isiadinso I., Wenger N.K. Do we need a different approach to assess cardiovascular risk in women? US Cardiol Rev. 2017;11(1):5.

23. Tanz L.J., Stuart J.J., Williams P.L. et al. Preterm delivery and maternal cardiovascular disease in young and middle-aged adult women. Circulation. 2017;135(6):578–89.

24. Bayanduryan E.A., Samburova N.V., Anichkova E.V. et al. Etiopathogenetic risk factors for stroke in pregnant women. [Etiopatogeneticheskie faktory riska razvitiya insul'ta u beremennyh]. Akusherstvo, Ginekologia i Reprodukcia. 2019;13(3):217–26. (In Russ.).

25. Pezzini A., Grassi M., Iacoviello L. et al. Inherited thrombophilia and stratification of ischaemic stroke risk among users of oral contraceptives. J Neurol Neurosurg Psychiatry. 2007;78(3):271–6. jnnp.2006.101675.

26. Mezhevitinova E.A., Khamoshin M.B., Rudneva O.D. et al. Hormonal contraception in high risk female patients: ways forward. [Gormonal'naya kontracepciya u zhenshchin vysokogo riska: puti resheniya problemy]. Doktor.Ru. 2012;(1):27–33. (In Russ.).

27. Wiesel M.L., Borg J.Y., Grunebaum L. et al. Influence of protein S deficiency on the arterial thrombosis risk. Presse Med. 1991;20(22):1023–7.

28. Douay X., Lucas C., Caron C. et al. Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke. Acta Neurol Scand. 1998;98(2):124–7.

29. Moster M. Coagulopathies and arterial stroke. J Neuroophthalmol. 2003;23(1):63–71.

30. Smith F.B., Lee A.J., Fowkes F.G. et al. Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol. 1997;17(11):3321–5.

31. Sukontseva T.A., Kaplina O.Yu. On the pathogenesis of thromboses in antiphospholipid syndrome. [K voprosu o patogeneze trombozov pri antifosfolipidnom sindrome]. Akusherstvo, Ginekologia i Reprodukcia. 2018;12(3):72–8. (In Russ.).

32. Urbanus R.T. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 2009;11(8):998–1005. S1474-4422(09)70239-X.


For citations:

Andreeva M.D., Novosartyan M.G., Samburova N.V., Khamani I.V. Cerebral circulation disorders in women using combined oral contraceptives. Obstetrics, Gynecology and Reproduction. 2021;15(2):173-181. (In Russ.)

Views: 517

ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)