This narrative review adopts an interpretivist/ subjectivist paradigm [15]. We synthesize evidence to illuminate how hormonal transitions across the female reproductive lifespan shape the clinical interplay between migraine and multiple sclerosis (MS), with an emphasis on implications for obstetric and gynecologic (OB-GYN) care. In keeping with narrative review traditions, we prioritize conceptual integration and contextual interpretation over exhaustive enumeration. The perspectives and disciplinary backgrounds of the authors informed question framing, the selection of seminal literature, and interpretation of findings; consequently, the insights are context- and time-bound and may vary across clinical settings and teams. We followed SANRA (Scale for the Assessment of Narrative Review Articles) to enhance transparency and relevance [16]. Registration of the review at Open Science Framework: http://osf.io/e7bkz

A purposeful, comprehensive search (January 2004–June 2025) was conducted in PubMed, Scopus, Web of Science, and Embase using controlled vocabulary and free-text terms related to migraine, MS, female reproductive health, and hormones (e.g., “migraine,” “multiple sclerosis,” “women,” “estrogen,” “menstrual cycle,” “pregnancy,” “postpartum,” “contraceptives,” “menopause,” “reproductive health,” “obstetrics,” “gynecology”). Reference lists of key publications and authoritative reviews were snowballed to identify additional influential articles. Search details and the selection pathway are summarized in Fig. (1).

Migraine are approximately three times more prevalent in women than in men, with women experiencing longer attack durations and greater disability. This disparity emerges after puberty and persists through menopause, highlighting the role of sex hormones in disease manifestation [17]. Similarly, MS exhibits a higher incidence in women, with a female-to-male ratio of about 3:1. This difference is most pronounced during reproductive years and diminishes after menopause [18, 19].

Hormonal fluctuations, particularly in estrogen levels, significantly impact both migraine and MS. In migraine, estrogen withdrawal is associated with increased attack frequency, as seen during menstruation and postpartum periods [20]. In MS, pregnancy, a state of elevated estrogen is linked to reduced relapse rates, suggesting a neuroprotective role of the hormone. Conversely, the postpartum drop in estrogen correlates with increased relapse risk [4].

The comparative analysis, as clarified in Table 1 highlights how hormonal fluctuations uniquely influence the clinical behavior of migraine and multiple sclerosis (MS) across key phases of the female reproductive lifespan. During puberty and the menstrual cycle, migraine symptoms often emerge or intensify due to estrogen withdrawal during the perimenstrual period [21]. In contrast, while early menarche has been associated with an increased risk of developing MS, the influence of cyclical hormonal changes on relapse activity in MS remains less clearly defined [22].

In pregnancy, both conditions generally show improvement. Migraine frequency tends to decrease, particularly in the second and third trimesters, mirroring the rise in stable estrogen levels [23]. Similarly, MS relapse rates significantly decline—up to 70% in the third trimester, suggesting a protective immunomodulatory effect of pregnancy-related hormones [24].

However, the postpartum period introduces a sharp decline in estrogen levels, often triggering a resurgence in symptoms. Migraine attacks frequently return or worsen [25], while MS patients face an elevated relapse risk, peaking around 3–4 months after delivery [7]. Some evidence suggests that breastfeeding, by maintaining hormonal stability, may help reduce the severity or timing of postpartum relapses in MS [26].

Regarding contraceptive use, estrogen-containing hormonal contraceptives can exacerbate migraines, particularly in women who experience migraine with aura, and may increase the risk of cerebrovascular events [27]. MS, however, does not appear to be significantly influenced by contraceptive hormones, although contraceptive choice should still be personalized based on the individual’s clinical profile and comorbidities [28].

Finally, during perimenopause and menopause, the decline and irregularity of estrogen can aggravate migraine frequency and severity. Some women may experience symptom relief post menopause [29]. In MS, early menopause has been correlated with an earlier transition to progressive disease and greater disability, likely linked to the loss of estrogen’s neuroprotective effects [30]. The details of Migraine and MS across the Female Reproductive Timeline are shown in Fig. (2).

Fertility outcomes in both multiple sclerosis (MS) and migraine are generally reassuring. In MS, most women maintain normal fertility [31], although subtle reductions in ovarian reserve may occur, especially in cases of high disease activity [32]. In contrast, migraine has no known direct impact on fertility, though stress and medication use may exert indirect effects [33].

Neither MS [34] nor Migraine [35] has been definitively linked to increased risks of miscarriage or congenital anomalies, reinforcing that pregnancy is generally safe in terms of fetal outcomes.

Regarding assisted reproductive technology (ART), earlier studies in MS raised concerns about a heightened relapse risk following hormonal stimulation. However, more recent evidence suggests that maintaining disease-modifying therapies (DMTs) significantly lowers relapse rates, making ART a safer option when managed appropriately [13]. For migraine, limited data exist on ART-specific effects, but no consistent evidence points to worsened outcomes following such interventions.

Medication management is critical in both populations. In MS, first-line DMTs such as interferons and glatiramer acetate are preferred during ART due to their favorable safety profiles [36]. For migraine, teratogenic medications like valproate should be avoided, and hormonal treatments may exacerbate symptoms in hormone-sensitive patients [37].

Pre-ART planning for MS includes disease stability assessment and ovarian reserve evaluation [13], whereas for migraine, the focus is on ensuring medication safety and symptom control [38]. Post-ART monitoring is especially important in MS, with neurological follow-up advised for 3–6 months [39]. Notably, cerebral venous sinus thrombosis has been reported following IVF, particularly in women with a history of migraine and underlying thrombophilia risk factors [40].

Multidisciplinary coordination is essential in both conditions. MS management requires collaboration between neurologists and fertility specialists, whereas in migraines, OB-GYN consultation is recommended to guide safe reproductive planning and medication adjustments.

The management of migraine and MS during pregnancy requires careful consideration of medication safety and disease control. Many disease-modifying therapies (DMTs) for MS are contraindicated during pregnancy due to potential teratogenic effects [6, 41]. Conversely, certain supplements including vitamin D, may be safely continued or initiated during pregnancy and lactation [42]. For migraines, non-pharmacological treatments are preferred, including lifestyle modifications and avoiding known triggers. When medication is necessary, acetaminophen is the first-line treatment, with nonsteroidal anti-inflammatory drugs and triptans regarded as secondary options, though trimester-specific risks limit their use. Preventive treatments, if required, may include low doses of β-blockers or amitriptyline but should be used cautiously [43].

Managing migraine and multiple sclerosis (MS) in women requires a collaborative and tailored approach, particularly during reproductive milestones such as preconception, pregnancy, and postpartum. OB-GYNs play a pivotal role in multidisciplinary coordination, especially when managing treatment safety and hormonal influences.

For hormonal management, non-hormonal contraceptives like copper IUDs are often preferred for women with migraine with aura due to stroke risk [44], meanwhile hormone therapies in MS may be beneficial when tailored, particularly with agents like high-dose estriol that demonstrate anti-inflammatory effects [45].

Preconception counseling is essential for both groups. Preconception counseling is crucial for women with migraine, as it can help optimize pregnancy outcomes and manage risks While migraine requires review of medication safety and nutritional support (e.g., folic acid, vitamin D) as studies have shown that pre-pregnancy migraine is associated with increased risks of adverse pregnancy outcomes, including preterm delivery, gestational hypertension, and preeclampsia [46], MS demands thorough assessment of disease stability and possible adjustments in DMTs before conception [47], Patients exposed to second/third-line DMTs like natalizumab and fingolimod before conception are at higher risk of MS reactivation during pregnancy [48]. ART procedures necessitate careful neurologic monitoring in MS [49].

In the postpartum period, hormonal shifts may trigger migraine exacerbations, best managed with non-pharmacologic options such as acupuncture [50]. MS patients face a high risk of relapse during this time, requiring prompt DMT resumption and blood pressure monitoring for potential preeclampsia [51].

Finally, Lifestyle modifications such as regular physical activity, sufficient sleep, and a heart-healthy diet offer benefits in managing both conditions [52, 53]. However, particular attention should be given to cognitive function in migraine patients, as the relationship between migraine and cognitive impairment is bidirectional. Migraines can lead to cognitive dysfunction, while cognitive decline may, in turn, aggravate migraine symptoms [54]. In patients with multiple sclerosis (MS), cognitive impairment is a major concern, affecting up to 65% and significantly diminishing quality of life [55]. Additionally, caution is warranted with medications like topiramate, commonly used in Migraine and MS, as they may further impair cognitive performance [56].

Hormone-linked clinical patterns and management considerations are summarized separately for migraine Table 1A and MS Table 1B.

Effective care for migraine and multiple sclerosis (MS) across the reproductive lifespan hinges on structured collaboration between neurology and obstetrics/ gynecology (OB/GYN). A unified referral route with agreed indications—such as hormonally sensitive migraine at menarche, pre-conception counseling in MS, contraception decisions in migraine with aura, trimester-specific medication review, postpartum relapse planning, and escalation at perimenopause—facilitates timely access. Shared electronic health records should include a concise “Reproductive–Neurologic Summary” (phenotype, disease activity trend, current/held medicines including DMTs, vascular risks, fertility/contraception plan, and the next hormone-stage milestone), while synchronized follow-ups anchor care at pivotal time-points (menarche/late adolescence, pre-conception, each trimester, early postpartum, and perimenopause). Contraceptive decisions are optimized by first classifying neurologic status (migraine with vs without aura; MS on or off DMTs, disability, and vascular comorbidity) and then balancing efficacy and vascular risk: combined estrogen methods are generally avoided in migraine with aura or high vascular risk and used selectively without aura; progestin-only methods are preferred when minimizing estrogen exposure and are typically acceptable in MS; non-hormonal options remain suitable at any stage. Pregnancy planning benefits from explicit checklists that confirm disease stability, specify DMT continuation/hold and washout timelines, adjust migraine preventives away from teratogens, and address vaccinations, thrombotic risk, and assisted reproduction. Antenatal care emphasizes diary-based monitoring, trimester-appropriate acute therapies, conservative MRI policies, and delivery planning, with peripartum protocols for postpartum relapse prevention, DMT resumption, and lactation-compatible regimens.

Postpartum and lactation pathways prioritize non-pharmacologic strategies for migraine, use lactation-compatible acute options where needed, and schedule MS reviews at ~6 weeks and 3–4 months to consider early DMT re-initiation and monitor hypertensive risk. Perimenopause and menopause management relies on individualized risk–benefit assessment that incorporates migraine subtype, MS status, vascular risks, and bone health; when indicated, low-dose transdermal estradiol with stable delivery is favored, with careful monitoring for aura change and MS activity and predefined thresholds for therapy adjustment. Patient-facing materials—plain-language stage-specific handouts and decision aids for contraception, pregnancy timelines with DMT checkpoints, and HRT risk–benefit grids—support shared decision-making; symptom diaries for headaches and relapses can be integrated through the patient portal. Service quality is tracked via pragmatic metrics, including postpartum MS relapse rate within six months and time-to-DMT resumption, migraine days per month during perimenopause and early postpartum, contraceptive method appropriateness in migraine with aura, timeliness of synchronized visits, documentation of lactation compatibility at discharge, presence of shared neurology–OB/GYN notes at key milestones, and patient-reported outcomes (satisfaction, decisional conflict, and health-related quality of life). These pathways translate hormone-informed evidence into coordinated, stage-specific practice that is auditable and adaptable.