Analysis of the relationship between migraine and climacteric syndrome in periand postmenopause

A history of migraine is a predictor of more frequent and severe vasomotor symptoms during periand postmenopause.

Objective: to study the connection between migraine and climacteric syndrome (CS) in periand postmenopausal patients.

Material and methods. The study included 120 female patients with migraine in periand postmenopause. The patients were divided into two groups: severe climacteric syndrome (CS; n=78) and mild CS (n=42).

Results. The risk of chronic migraine, frequent migraine attacks, high pain intensity during attacks, severe impact of headache on quality of life, severe maladjustment of patients with migraine, severe burden of migraine outside attacks, and insufficient response to headache treatment was significantly higher in the severe CS group than in the non-severe group (p<0.05). In the group of patients with severe migraine, the risk of clinically significant anxiety and clinically significant depression was significantly higher than in the group with mild migraine (p<0.05). When constructing a multiple linear regression model, it was found that MIBS-4 scores, mental health and role functioning due to emotional state (SF-36), anxiety and depression (HADS) can predict the Green Climacteric Scale score in patients with migraine in periand postmenopause (F=25.2; Fcrit=2.29; p<0.05).

Conclusion. The course of migraine in patients with severe manifestations of CS is less favourable than in patients with mild CS. The course of migraine and the mental status of patients can influence the severity of CS, and vice versa. Further research is needed to identify the causes of the observed phenomena.

1. Menopause and climacteric state in women: clinical guidelines. Russian Society of Obstetricians and Gynecologists. Moscow: Ministry of Health of the Russian Federation; 2025. ID: 117_3 (In Russ.).

2. Lee E, Anselmo M, Tahsin CT, et al. Vasomotor symptoms of menopause, autonomic dysfunction, and cardiovascular disease. Am J Physiol Heart Circ Physiol. 2022;323(6):H1270H1280. doi: 10.1152/ajpheart.00477.2022

3. Waliszewska-Prosol M, Grandi G, Ornello R, et al. Menopause, perimenopause, and migraine: Understanding the intersections and implications for treatment. Neurol Ther. 2025;14(3):665-80. doi: 10.1007/s40120-025-00720-2

4. Gupta S, Villalon CM, Mehrotra S, et al. Female sex hormones and rat dural vasodilatation to CGRP, periarterial electrical stimulation and capsaicin. Headache. 2007;47(2):225-35. doi: 10.1111/j.1526-4610.2006.00526.x

5. Guo JQ, Deng HH, Bo X, Yang XS. Involvement of BDNF/TrkB and ERK/CREB axes in nitroglycerin-induced rat migraine and effects of estrogen on these signals in the migraine. Biol Open. 2017;6(1):8-16. doi: 10.1242/bio.021022

6. Martin VT, Pavlovic J, Fanning KM, et al. Perimenopause and menopause are associated with high frequency headache in women with migraine: results of the American Migraine Prevalence and Prevention Study. Headache. 2016:56(2):292-305. doi: 10.1111/head.12763

7. Ornello R, Caponnetto V, Frattale I, Sacco S. Patterns of Migraine in Postmenopausal Women: A Systematic Review. Neuropsychiatr Dis Treat. 2021;17:859-71. doi: 10.2147/NDT.S285863

8. Saffari TM, Kavanagh K, Ormseth B, et al. Severe obesity is associated with increased migraine severity and frequency: A retrospective cohort study. J Clin Neurosci. 2023;115:8-13. doi: 10.1016/j.jocn.2023.07.007

9. Maleki N, Cheng YC, Tu Y, Locascio JJ. Longitudinal course of vasomotor symptoms in perimenopausal migraineurs. Ann Neurol. 2019;85(6):865-74. doi: 10.1002/ana.25476

10. Sabia S, Fournier A, Mesrine S, et al. Risk factors for onset of menopausal symptoms: results from a large cohort study. Maturitas. 2008;60(2):108-21. doi: 10.1016/j.maturitas.2008.04.004

11. Faubion SS, Smith T, Thielen J, et al. Association of Migraine and Vasomotor Symptoms. Mayo Clin Proc. 2023;98(5):701-12. doi: 10.1016/j.mayocp.2023.01.010

12. Crowe HM, Rich-Edwards JW, Rexrode KM, Joffe H. Association of migraine and vasomotor symptom severity and duration among naturally menopausal women in Nurses’ Health Study II. Menopause. 2025. doi: 10.1097/GME.0000000000002615

13. Karimi L, Wijeratne T, Crewther SG, et al. The Migraine-Anxiety Comorbidity Among Migraineurs: A Systematic Review. Front Neurol. 2021;11:Art. 613372. doi: 10.3389/fneur.2

14. Amiri S, Behnezhad S, Azad E. Migraine headache and depression in adults: A systematic review and meta-analysis. Neuropsychiatry. 2019;33(3):131-40. doi: 10.1007/s40211-018-0299-5

15. Xu J, Kong F, Buse DC. Predictors of episodic migraine transformation to chronic migraine: A systematic review and meta-analysis of observational cohort studies. Cephalalgia. 2020;40(5):503-16. doi: 10.1177/0333102419883355

16. Gibson CJ, Ajmera M, O’Sullivan F, et al. A systematic review of anxiety and depressive symptoms among women experiencing vasomotor symptoms across reproductive stages in the US. Int J Womens Health. 2025;17:537-52. doi: 10.2147/IJWH.S491640

17. Alblooshi S, Taylor M, Gill N. Does menopause elevate the risk for developing depression and anxiety? Results from a systematic review. Australas Psychiatry. 2023;31(2):165-73. doi: 10.1177/10398562231165439

18. Ministry of Health of the Russian Federation. Clinical guidelines. Migraine. All-Russian Society of Neurologists, All-Russian Public Organization "Union of Rehabilitologists of Russia", Interregional Public Organization "Russian Society for the Study of Headache". 2024. ID: 295_4 (In Russ.).

19. Tabeeva GR, Artemenko AR, Koreshkina MI, et al. Overcoming obstacles to effective treatment of patients with migraine (Statement of the expert group on optimizing treatment of patients with migraine). Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2025;17(2):414 (In Russ.). doi: 10.14412/2074-2711-2025-2-4-14

20. Diener HC, Gaul C, Lehmacher W, Weiser T. Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: A systemic review and meta-analysis of randomized placebo-controlled trials. Eur J Neurol. 2022;29(1):350-7. doi: 10.1111/ene.15103

21. Tabeeva GR. Rational approach to migraine attacks relief. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2025;17(2):100-6 (In Russ.). doi: 10.14412/2074-2711-2025-2-100-106

22. Pellesi L, Jedie B, Barhum F, et al. Headto-head relief: ubrogepant, rimegepant, and zavegepant in migraine treatment. Pain Manag. 2025;15(5):279-84. doi: 10.1080/17581869.2025.2494494

23. Yang CP, Liang CS, Chang CM, et al. Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis. JAMA Network Open. 2021;4(10):e2128544. doi: 10.1001/jamanetworkopen.2021.28544

24. Lanteri-Minet M, Ducros A, Francois C, et al. Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. Cephalalgia. 2022 Dec;42(14):1543-64. doi: 10.1177/03331024221123058

25. Artemenko AR, Abramov VG. Botulinum toxin type A (Relatox) in the treatment of chronic migraine in adults: results of phase IIIb, randomized, one-blind, multicenter, activecontrolled, parallel-group trial. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(5):89-99 (In Russ.). doi: 10.17116/jnevro202312305189

26. Tabeeva GR, Kosivtsova OV, Kovalchuk NA, Orlyuk TA. Refractory migraine. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2024;16(2):7686 (In Russ.). doi: 10.14412/2074-2711-2024-2-76-86

27. Diener HC, Dodick DW, Turkel CC, et al. Pooled analysis of the safety and tolerability of onabotulinumtoxinA in the treatment of chronic migraine. Eur J Neurol. 2014;21(6):851-9. doi: 10.1111/ene.12393

28. Sevivas H, Fresco P. Treatment of resistant chronic migraine with anti-CGRP monoclonal antibodies: a systematic review. Eur J Med Res. 2022;27(1):Art. 86. doi: 10.1186/s40001-022-00716-w

29. Vernieri F, Iannone LF, Lo Castro F, et al.; Italian Headache Registry (RICe) Study Group. Effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study). Cephalalgia. 2025;45(4):3331024251335927. doi: 10.1177/03331024251335927

30. Hou M, Luo X, He S, et al. Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: a systematic review and meta-analysis. J Headache Pain. 2024;25(1):116. doi: 10.1186/s10194-024-01822-2

31. Aegidius KL, Zwart JA, Hagen K, et al. Hormone replacement therapy and headache prevalence in postmenopausal women. The Head-HUNT study. Eur J Neurol. 2007;14(1):73-8. doi: 10.1111/j.1468-1331.2006.01557.x

32. Kim S, Lee SB, Hong YJ, et al. The influence of endogenous and exogenous hormonal factors on migraine in spontaneous postmenopausal women: A nationwide population-based study in South Korea. Cephalalgia. 2022;42(4-5):376-84. doi: 10.1177/03331024211044441

33. Ripa P, Ornello R, Degan D, et al. Migraine in menopausal women: a systematic review. Int J Women's Health. 2015;7:773-82. doi: 10.2147/IJWH.S70073

34. Witten T, Staszkiewicz J, Gold L, et al. Nonhormonal Pharmacotherapies for the Treatment of Postmenopausal Vasomotor Symptoms. Cureus. 2024 Jan 17;16(1):e52467. doi: 10.7759/cureus.52467

35. Chavez MP, Pasqualotto E, Ferreira ROM, et al. Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis. Climacteric. 2024 Jun;27(3):245-54. doi: 10.1080/13697137.2024.2334083

36. Santoro N, Neal-Perry G, Stute P, et al. Fezolinetant effect on vasomotor symptoms due to menopause in women unsuitable for hormone therapy. Curr Med Res Opin. 2025 Feb;41(2):375-84. doi: 10.1080/03007995.2025.2470752

37. Soong RY, Low CE, Ong V, et al. Exercise Interventions for Depression, Anxiety, and Quality of Life in Older Adults With Cancer: A Systematic Review and MetaAnalysis. JAMA Network Open. 2025;8(2):e2457859. doi: 10.1001/jamanetworkopen.2024.57859

38. La Touche R, Fierro-Marrero J, Sanchez-Ruiz I, et al. Prescription of therapeutic exercise in migraine, an evidence-based clinical practice guideline. J Headache Pain. 2023 Jun 7;24(1):68. doi: 10.1186/s10194-023-01571-8

39. Thomas A, Daley AJ. Women’s views about physical activity as a treatment for vasomotor menopausal symptoms: a qualitative study. BMC Women’s Health. 2020 Sep 14;20(1):203. doi: 10.1186/s12905-020-01063-w