Efficacy and safety of rimegepant in Chinese women with pure menstrual migraine: a retrospective observational study.

Data from menstrual migraine patients treated with rimegepant was collected for this retrospective observational study. The study was approved by the ethics committee of the Second Affiliated Hospital of Soochow University (approval number JD-LK2024055-A01). The requirement for informed consent was waived by the Ethics Committee of the Second Affiliated Hospital of Soochow University due to the retrospective nature of the study. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. In this study, we analyzed data from female patients with pure menstrual migraine who had received perimenstrual prophylaxis with rimegepant. The data were derived from the routine electronic medical records (EMR) system of the Headache Outpatient Center at the Second Affiliated Hospital of Soochow University. In this study, rimegepant was used exclusively as perimenstrual prophylaxis. There was no documented use of rimegepant as an on-demand acute medication in the included cohort. Patients diagnosed with pure menstrual migraine according to the International Classification of Headache Disorders, third edition [ 2 ] (migraine attacks occurring in at least 2 of the past 3 consecutive menstrual cycles, with attacks exclusively occurring during the perimenstrual period). The perimenstrual period refers to the period from 2 days before to the third day of menstruation. Additionally, patients were required to aged over 18 and have self-reported regular menstrual cycles in the 3 months preceding the initiation of rimegepant treatment. Patients with any of the following documented in their medical records were not included in the final analysis: (1) use of oral contraceptives, hormone replacement therapy, or any other migraine prophylactic medication within the 3 months prior to starting perimenstrual rimegepant prophylaxis; (2) experience of ≥ 1 non- perimenstrual migraine attack during the period of perimenstrual rimegepant prophylaxis; (3) pregnancy, lactation, severe psychiatric disorders, or serious cardiovascular/cerebrovascular conditions; (4) lack of complete baseline or follow-up questionnaire data required for the analysis. (5) self-reported irregular menstrual cycles that significantly affected the prediction. Patients’ demographic and migraine characteristic information were derived from the routine electronic medical records. According to the records, eligible patients were prescribed and took 75 mg rimegepant orally disintegrating tablets sublingually every other day during the perimenstrual period across three consecutive menstrual cycles. The first day of menstruation was defined as Day 0. Dosing occurred on Days − 2, 0, and + 2 relative to menstruation onset. The expected onset of menstruation was estimated by treating physicians based on patients’ self-reported menstrual history (cycle length and duration from the last menstrual period prior to treatment initiation), as part of routine clinical care. Data extracted from patients’ medical records included peri-menstrual headache frequency (PHD), severity (using VAS scores [ 9 , 10 ]), duration, disability level (MIDAS scales [ 11 ]), impact on daily life (HIT-6 scales [ 12 ]), psychiatric condition (HAMA [ 13 ], HAMD [ 14 ], and PSQI scales [ 15 ]), acute medication intake, and adverse events, These parameters were routinely documented during scheduled monthly or perimenstrual follow-up visits, which often utilized standardized online questionnaires and electronic diaries as part of the center’s clinical practice. MIDAS scores were collected at baseline and month 3. The baseline MIDAS score was obtained at treatment initiation, reflecting disability during the three months prior to treatment; the month 3 score was obtained at the final follow-up visit, reflecting disability during the three‑month treatment period. Visual Analogue Scale (VAS) is a tool quantifying pain intensity using a visual ruler, commonly used to assess patients’ subjective headache perception. The scale consists of a 100 mm line, with one end representing no pain, while the other end represents the most serious pain that can be imagined. Patients were required to mark the corresponding position on the line to indicate their perceived pain intensity. Migraine Disability Assessment Questionnaire (MIDAS) is a simple, self-administered questionnaire that quantitatively assesses migraine-related disability over a 3-month period, enabling a quantitative evaluation of disability severity. Headache Impact Test 6 (HIT-6) is a questionnaire assessing headache’s impact on work, family, and social activities based on the patient’s experience over the past 4 weeks. It includes 6 questions covering pain, social role functioning, cognitive function, psychological distress, and energy levels, effectively evaluating headache-related quality of life and treatment efficacy. Ratings range from 36 to 78, with higher scores indicating greater impact on daily life. The primary outcome was the change from baseline in attack duration during the course of the 3-cycle treatment period. Attack duration was defined as the mean duration of a single migraine attack per perimenstrual period, recorded via electronic diary and based on ICHD-3 criteria [ 2 ]. The secondary efficacy endpoints involved the mean change from baseline in PHD and migraine intensity, change from baseline in the Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Hamilton Anxiety Scale-14 (HAMA-14), Hamilton Depression Scale-17 (HAMD-17) and Pittsburgh Sleep Quality Index (PSQI) scores, change from baseline in the proportion of patients using acute medication, as well as the proportion of patients with a ≥ 50% and ≥ 75% reduction from baseline in PHD. The frequency of adverse events (AEs) and significant adverse events (sAEs) was included in the safety analysis. Statistical analysis was conducted using SPSS 25.0 statistical software. We conducted descriptive statistics to summarize demographic and clinical characteristics at baseline. Variables were assessed for normality of distribution by evaluating skewness and kurtosis. Categorical variables were displayed as frequencies and percentages. Continuous variables were represented as mean±standard deviation (SD). Changes from baseline in effectiveness variables were evaluated using mixed-effect model repeated measurements (MMRM) analysis and post-hoc Bonferroni’s correction. The model included time as a fixed variable, participants as a randomized variable, age, marriage, and BMI as covariates. AR1was used to model the within-subject correlations. The data were shown as differences, 95% CI, and the p -value. Missing data of individuals are controlled using the mixed-effect model analysis. The Wilcoxon nonparametric test was used for intergroup comparisons of continuous variables, while the chi-square test was employed for intergroup comparisons of categorical variables. As this was a retrospective analysis based on the medical records, no formal power calculation was performed. The sample size was determined by the number of eligible patients identified within the study period.

In this study, only 2 patients reported mild adverse events such as nausea. The nausea symptoms reported by patients were relatively mild and tolerable. No serious adverse events or discontinuation of treatment due to adverse events were reported.

Data of 43 patients was collected in this study. All 43 patients completed the 3-month treatment and follow-up, with no missing outcome data at any time point. The menstrual cycle range for women in this population was 27–32 days. The mean age of patients was 37.0 (5.2) years, with a mean BMI of 22.3 (1.8) kg/m². 90.7% of patients were married, 18.6% consumed alcohol, and 4.7% smoked. The mean age at onset of migraine was 26.7 (5.1) years, with an average disease history of 10.3 (5.3) years. Baseline demographic and clinical characteristics are summarized in Table  1 . Table 1 Baseline demographics and clinical features Total ( n  = 43) Age, mean (SD) 37.0 (5.2) BMI, mean (SD) 22.3 (1.8) Marriage, n (%) 39 (90.7) Drinking, n (%) 8 (18.6) Smoking, n (%) 2 (4.7) Age of onset, mean (SD) 26.7 (5.1) Education, mean (SD) 10.8 (4.0) Migraine history, mean (SD) 10.3 (5.3) Duration in hours, mean (SD) 23.2 (13.7) PHD, mean (SD) 1.7 (0.5) PSQI, mean (SD) 4.7 (2.1) VAS, mean (SD) 8.1 (1.0) MIDAS, mean (SD) 16.7 (2.6) HIT-6, mean (SD) 47.7 (2.6) HAMD-17, mean (SD) 5.3 (2.9) HAMA-14, mean (SD) 5.1 (2.8) Nausea, n (%) 43 (100) Vomiting, n (%) 34 (79.1) Photophobia, n (%) 34 (79.1) Phonophobia, n (%) 34 (79.1) Acute medication use, n (%) 41 (95.4)  Ibuprofen, n (%) 23(53.5)  Celecoxib, n (%) 2 (4.7)  Triptans, n (%) 2 (4.7)  Analgesic Combinations, n (%) 14 (32.6) Analgesic Combinations include Aspirin/Paracetamol/Caffeine/Aminophenazone/Phenobarbital/Allylisopropylacetylurea BMI body mass index, PHD peri-menstrual headache day, PSQI Pittsburgh Sleep Quality Index, VAS Visual analog Scale, MIDAS Migraine Disability Assessment questionnaire, HIT-6  6-item Headache Impact Test, HAMA Hamilton Anxiety Rating Scale, HAMD Hamilton Depression Rating Scale, SD standard deviation Baseline demographics and clinical features Analgesic Combinations include Aspirin/Paracetamol/Caffeine/Aminophenazone/Phenobarbital/Allylisopropylacetylurea BMI body mass index, PHD peri-menstrual headache day, PSQI Pittsburgh Sleep Quality Index, VAS Visual analog Scale, MIDAS Migraine Disability Assessment questionnaire, HIT-6  6-item Headache Impact Test, HAMA Hamilton Anxiety Rating Scale, HAMD Hamilton Depression Rating Scale, SD standard deviation At baseline, patients experienced an average of 1.7 (0.5) perimenstrual migraine attacks days per month, with an average lasting of 23.2 (13.7) hours. Most patients had two or more migraine-associated symptoms; all patients experienced nausea (100%), 34 patients experienced vomiting (79.1%), 34 patients experienced photophobia (79.1%), and 34 patients experienced phonophobia (79.1%). Baseline VAS scores were 8.1 (1.0), and 90.7% of patients had VAS scores exceeding 7 points, indicating a severe headache. The mean MIDAS score was 16.7 (2.6), and the mean HIT-6 score was 47.7 (2.6). Patients’ HAMA-14, HAMD-17, and PSQI scores were 5.1 (2.8), 5.3 (2.9), and 4.7 (2.1), respectively. 95.4% of patients took acute medications during migraine attacks to relieve headache, 62.9% of patients use recommended acute medication, such as ibuprofen (53.5%), celecoxib (4.7%), and triptans (4.7%), while 32.6% of patients take an analgesic combination, which contains ingredients such as caffeine, phenobarbital, allylisopropylacetylurea, and aminophenazone. For the primary endpoint, after three cycles of short-term preventive treatment, rimegepant significantly shortened the attack duration by -20.5 h (-24.7, -16.2; p  < 0.001), with an average monthly reduction of 6.9 h. For secondary endpoints, rimegepant reduced PHD by 1.1 days, with an average monthly reduction of 0.4 days. Patients’ headache intensity decreased from 8.1 points at baseline to 2.2 points at study completion, representing a reduction of -6.0 points (95% CI -7.0, -5.0; p  < 0.001), with an average monthly decrease of 2.0 points. The HIT-6 score decreased significantly during the first two months, reaching a reduction of -11.4 points by the end of month 3. The MIDAS score decreased from 16.7 (2.6) at baseline to 6.6 (2.2) at study completion, indicating improved disability due to migraine and enhanced quality of life. Rimegepant did not improve mood or sleep outcomes in this population. After three months of treatment, no significant changes were observed in HAMA-14, HAMD-17, or PSQI scores compared to baseline ( Table  2 ) . Table 2 Efficacy endpoints over the three-month period Baseline Month 1 Month 2 Month 3 Change from baseline (95% CI) β p value Primary endpoint Duration 23.2 (13.7) 11.4 (7.7) 4.6 (4.4) 2.7 (3.5) -20.5(-24.7, -16.2) -6.9 <0.001 Secondary endpoints PHD 1.7 (0.5) 1.2 (0.6) 0.8 (0.6) 0.6 (0.5) -1.1 (-1.4, -0.8) -0.4 <0.001 VAS scores 8.1 (1.0) 5.7 (2.1) 3.1 (2.5) 2.2 (2.1) -6.0(-7.0, -5.0) -2.0 <0.001 HIT-6 scores 47.7 (2.5) 42.5 (4.1) 37.4 (2.4) 36.4(1.3) -11.4(-12.4, -10.3) -3.6 <0.001 MIDAS scores 16.7 (2.6) - - 6.6 (2.2) -10.1(-10.6, -9.6) - <0.001 HAMA-14 scores 5.1 (2.7) 5.3 (2.6) 5.6 (2.3) 5.2 (2.5) 0.1(-0.8, 1.0) -0.03 0.788 HAMD-17 scores 5.4 (2.9) 4.9 (2.5) 5.1 (2.5) 5.2 (3.0) -0.1(-1.0, 0.7) -0.04 0.745 PSQI-scores 4.6 (2.1) 4.9 (1.7) 5.1 (1.6) 4.6 (0.6) -0.04(-0.75, 0.67) -0.01 0.903 Efficacy endpoints over the three-month period After receiving treatment with rimegepant, 39.53%, 61.90%, and 76.70% of patients achieved a response exceeding 50% at 1, 2, and 3 months, respectively. Additionally, 9.30%, 32.60%, and 44.20% of patients received a response exceeding 75% at these respective time points (Fig.  1 ). Fig. 1 Patients with ≥50% and ≥75% reduction from baseline in migraine days per Patients with ≥50% and ≥75% reduction from baseline in migraine days per Over the 3-cycle treatment period, a significant reduction in the use of acute medications was also observed, with utilization rates declining to 79.07%, 34.88%, and 13.95% from a baseline of 95.35% over the same period ( Fig.  2 ) . Fig. 2 Patients with acute-medication free change from baseline per month Patients with acute-medication free change from baseline per month

In this retrospective, uncontrolled study, short-term prophylactic use of rimegepant was associated with reductions in perimenstrual headache days, duration, and severity, as well as improvements in quality of life and disability among patients with pure menstrual migraine. However, given the study design, these findings should be interpreted as associations rather than causal effects, and warrant further investigation in rigorous, controlled trials to establish its efficacy for the prevention of pure menstrual migraine.

Our study evaluated the effectiveness and safety of rimegepant for short-term prophylactic treatment in patients with pure menstrual migraine. The results suggested that short-term preventive use of rimegepant was associated with reduced migraine burden and was well-tolerated in this cohort. In this study, Administration of 75 mg every other day was associated with significant reductions in attack frequency and headache intensity, alongside improvements in patients’ quality of life. These preliminary data indicate that rimegepant may represent a potential preventive strategy for pure menstrual migraine. To our knowledge, this is among the first studies exploring rimegepant specifically for pure menstrual migraine. Perimenstrual migraine attack refers to attacks that occur during a period from two days before to three days after menstruation. Compared to attacks during other phases of the menstrual cycle, perimenstrual attacks are characterized by greater intensity, longer lasting, higher disability, and less response to treatments. Current research suggested that the estrogen withdrawal hypothesis is the primary pathophysiological mechanism underlying menstrual migraine. Estrogen fluctuates with menstrual cycle regularly and declines precede the start of menstruation. Clinical evidence indicates that in susceptible women, a sharp decline in estrogen level following sustained exposure to estrogen over a period of time can trigger migraine attacks [ 16 ]. Research showed that during the late luteal phase and early follicular phase, when estrogen levels are low, migraine frequency tends to be higher, while as estrogen levels rise, migraine frequency decreases [ 17 ]. A study evaluating changes in sex hormone levels among female migraine sufferers found that urinary estrogen levels in migraine patients appeared to decline more rapidly during the luteal phase compared to patients in the control group [ 18 ]. The exact mechanism remains unknown, while evidence from neuroimaging indicated that estrogen may trigger migraine attacks by influencing the connectivity of some crucial pain circuits, thus leads to the cyclical changes of pain threshold [ 4 , 19 ]. Recently, studies have elucidated the relationship between estrogen fluctuations and nociceptive neuropeptides. Calcitonin gene-related peptide (CGRP), a key factor in migraine pathogenesis, is revealed to be influenced by estrogen fluctuation [ 4 , 20 , 21 ]. Research indicates that CGRP levels vary across the menstrual cycle, with distinct patterns observed in women with migraine and endometriosis comorbidity [ 22 ]. Study based on women with episodic migraine and a regular menstrual cycle exhibit significantly higher interictal CGRP concentrations in both plasma and tear fluid specifically during menstruation, compared to those without migraine. However, this elevation was not observed in women under combined oral contraception or in postmenopause, indicating the unique link between natural hormonal fluctuations and CGRP release in migraine pathophysiology [ 23 ]. Evidence suggested that estrogen can modulate the production and release of CGRP, and an animal study using ERβ −/− mice revealed that knocking out the gene of ERβ led to an increase in CGRP level in the dorsal horn, suggesting estrogen may suppress the CGRP system [ 5 ]. Another study using ovariectomized rat models demonstrated that estrogen deficiency correlates with increased levels of CGRP in the trigeminal ganglia and midbrain periaqueductal gray [ 24 , 25 ]. Therefore, therapy targeting the CGRP system may represent an effective treatment approach for menstrual migraine. Recently, a number of clinical studies have confirmed the effectiveness of anti- CGRP monoclonal antibodies (anti-CGRP mAbs) and CGRP receptor antagonist in both acute and preventive treatment for migraine. In the aspect of CGRP-mAb, a meta-analysis demonstrated that CGRP-mAb (erenumab and galcanezumab) showed better effectiveness in menstrual migraine than traditional preventive medication, such as triptans and naproxen, with fewer adverse events [ 26 ]. A cohort study compared BTX-A and CGRP-mAbs (included erenumab, fremanezumab, and galcanezumab) indicated that both of these can decrease the frequency of migraine attacks over the whole menstrual cycle but have a limited effect on perimenstrual attacks [ 27 ]. However, limited studies explored the effectiveness of the CGRP receptor antagonist in menstrual migraine. Previous randomized study assessing the efficacy of telcagepant in menstrual migraine was proven to be effective, but the risk of hepatotoxicity limited its further application [ 28 ]. Rimegepant, a CGRP receptor antagonist, has demonstrated effective and well-tolerated in numerous studies for both the acute and preventive treatment of migraine. The first real-world study of rimegepant for acute migraine treatment in Chinese patients, which included a subgroup where 71% reported menstruation-related migraine, showed good overall efficacy and tolerability [ 8 ]. However, its effectiveness specifically for menstrual migraine had not been established prior to this study. In this study, we observed significant improvements in attack duration, PHD, severity, and life quality in patients with pure menstrual migraine following three cycles of short-term preventive treatment with 75 mg rimegepant. At baseline, all patients experienced moderate to severe headache intensity, with 91% reporting severe migraine attacks (VAS ≥ 7 points) and 95.4% experiencing migraine attacks lasting more than half a day, indicating a substantial headache burden in this population. During the treatment period, patients achieved an average monthly improvement of 2.0 points in headache severity and 6.9 h in headache duration. At baseline, patients had an average MIDAS score of 16.7 and a HIT-6 score of 47.7. After 3 months of treatment, the MIDAS score improved by 10.1 points and the HIT-6 score improved by 11.4 points, both meeting the criteria for clinically meaningful disability improvement as defined by the American Headache Society guidelines. Additionally, we conducted an exploratory subgroup analysis to assess treatment efficacy across different age groups. We selected 40 years as the cutoff, based on evidence that physiological ovarian aging and hormonal changes begin around this age [ 29 ], which may render women more susceptible to menstrual migraine [ 30 ]. Baseline characteristics were comparable between the two groups, except for disease duration and history of drinking, which were expected given the age difference. Results from the stratified analysis indicate that after 3 cycles of treatment with rimegepant, younger patients (< 40 years) demonstrated greater improvement in headache frequency compared to older patients(≥ 40 years), suggesting that younger patients may receive greater benefit. This discrepancy may be explained by the altered hormonal milieu and a higher degree of central sensitization associated with longer migraine history in older patients [ 31 ]. We did not observe any difference in other migraine indicators, such as duration and severity. This lack of difference may be attributed to the limited sample size and the inclusion criteria, since our study only involved patients with regular cycles and excluded those with menstrual irregularities. Therefore, larger future studies stratifying by STRAW + 10 criteria are needed to evaluate rimegepant’s efficacy specifically across the menopausal transition. Our study has several limitations. Firstly, the single-arm design, relying on within-patient comparisons without a placebo control, introduces the possibility of placebo effects. Consequently, this design cannot establish causal efficacy between rimegepant use and the observed improvement. The observed improvements may be partly attributable to regression to the mean and natural menstrual variability, as patients typically seek treatment during periods of heightened symptoms, and menstrual migraine frequency fluctuates naturally between cycles. We cannot exclude the possibility that these factors contributed to the reported outcomes. Secondly, to avoid external influences on menstrual cyclicity, we excluded patients using hormonal treatments, contraceptive medications, as well as those who were pregnant. This criterion also systematically excluded women with irregular menstrual cycles, including some perimenopausal women. Consequently, The efficacy of rimegepant for women across the menopausal transition remains to be elucidated in future prospective studies. The small sample size and strict exclusion criteria may limit the generalizability of the findings to real-world patients with pure menstrual migraine. However, this design helps isolate the effect of drugs and external hormone influence on the disease by minimizing confounding factors. Thirdly, the data in this study were derived from a specific usage pattern where rimegepant was prescribed exclusively as perimenstrual short-term prophylaxis. Our retrospective review confirmed no additional use of the rimegepant for acute rescue within this cohort. While this design helps to isolate and evaluate its pure preventive effect, it also implies that our findings do not capture the potential real-world scenario where some patients may employ a flexible dosing strategy with both prevention and acute treatment. Future prospective studies investigating such flexible strategies would be of significant value. Additionally, we included only patients with self-reported regular menstrual cycles over the preceding three months, this criterion facilitated the selection of patients with pure menstrual migraine and was necessary to ensure preventive treatment within a fixed perimenstrual window. However, the reliance on patient self-reporting is subject to recall bias. Therefore, extrapolation of the results requires caution.

We further classified patients based on age to investigate whether there were differences in the efficacy of rimegepant between women of different age groups. Stratified analysis revealed that baseline demographic and clinical characteristics were generally comparable between the two groups, with the exception of age, disease duration, and alcohol consumption. After a 3-cycle period of treatment, younger patients (aged < 40 years) demonstrated a significantly greater improvement in PHD compared to older patients (aged ≥ 40 years) (1.0 ± 0.6 vs. 0.5 ± 0.5, p  = 0.016), suggesting that younger patients may respond better to rimegepant in terms of reducing migraine frequency ( Table  3 ) . However, no significant differences were observed between the two age groups in other migraine indicators, including pain severity (VAS), attack duration, or HIT-6 scores (all p  > 0.05). Table 3 Baseline characteristics and efficacy endpoints between patients with different age stages Patients aged < 40 years Patients aged ≥ 40 years p ( n  = 29) ( n  = 14) Age, mean (SD) 34.4 (4.2) 42.3 (1.9)  0.999 Marriage, n(%) 25 (86.2) 14 (100.0) 0.286 Migraine History, mean (SD) 8.1 (3.8) 14.7 (5.3)  0.999 Vomiting, n (%) 8 (27.6) 1 (7.1) 0.231 Photophobia, n (%) 7 (24.1) 2 (14.3) 0.693 Phonophobia, n (%) 5 (17.2) 4 (28.6) 0.442 Baseline PHD, mean (SD) 1.8 (0.5) 1.5 (0.5) 0.136 △PHD, mean (SD) 1.0 (0.6) 0.5 (0.5) 0.016 Baseline Duration, mean (SD) 22.8 (14.2) 25.1 (13.7) 0.608 △ Duration, mean (SD) 16.7 (13.7) 18.7 (13.6) 0.657 Baseline VAS, mean (SD) 8.1 (1.1) 8.2 (0.8) 0.627 △ VAS, mean (SD) 4.6 (2.2) 4.2 (1.2) 0.435 Baseline MIDAS, mean (SD) 16.6 (2.9) 16.7 (1.8) 0.898 △ MIDAS, mean (SD) 10.4 (4.0) 9.4 (1.1) 0.193 △ HIT-6, mean (SD) 11.3 (2.9) 11.3 (2.9) 0.961 Baseline HAMD-17, mean (SD) 5.8 (3.43) 4.5 (1.2) 0.084 Baseline HAMA-14, mean (SD) 5.5 (3.19) 4.4 (1.3) 0.101 Baseline PSQI, mean (SD) 4.9 (2.4) 4.1 (1.4) 0.173 Baseline characteristics and efficacy endpoints between patients with different age stages

Migraine is a debilitating condition with 14% of the worldwide population affected. Female individuals are more susceptible than males, with prevalence twice more than that of men (18.9% vs. 9.8%) [ 1 ]. Additionally, some female migraine sufferers experience attacks that appear to be frequently associated with the menstrual cycle, and these subtypes of migraine are defined by term menstrual migraine, which includes pure menstrual migraine (migraine attacks strongly associated with menstrual cycle and exclusively occurs during menstruation) and menstrual related migraine (migraine strongly relates to menstrual cycle and not only occurs during mentruation, but also exist in other part of menstrual cycle) [ 2 ]. Compared to typical migraine, menstrual migraine frequently presents with longer lasting, more severe intensity, higher disability, and less response to medication, thereby making treatment more challenging. According to a population-based study, menstrual migraine affects around 22.0% of female patients with migraine, imposing a significant burden on this population [ 3 ]. The exact pathogenesis of menstrual migraine remains unclear. The strong correlation between the menstrual cycle and migraine attacks suggests a mechanism distinct from that of episodic migraine. Currently, the estrogen withdrawal hypothesis is considered to be the main mechanism underlying this type of migraine. During the perimenstrual period (from 2 days before to the third day of menstruation), the level of estrogen decreased significantly, and migraine attacks were triggered [ 4 ]. Calcitonin gene-related peptide (CGRP) is a crucial neuropeptide in migraine mechanisms, and recent evidence has revealed the potential interaction between CGRP and estrogen. Estrogen suppresses the expression and release of CGRP, and its withdrawal leads to an increase in CGRP [ 5 ]. Therefore, the use of CGRP-targeting drugs during the perimenstrual period may serve as an effective therapeutic approach for improving menstrual migraine. Treatment for menstrual migraine includes acute treatment, short-term preventive treatment, as well as long-term preventive treatment. Researches have demonstrated the effectiveness of triptans, lasmiditan, and naproxen for menstrual migraine [ 6 ]. However, compared to typical migraine, the medication alteration is still limited. Real-world evidence demonstrated that CGRP-mAb (including galcanezumab, fremanezumab, and erenumab) reduced frequency, intensity, lasting of menstrual migraine, as well as improved the response to painkillers [ 7 ]. A real-world study focused on acute treatment conducted by Yang et al. [ 8 ] provides initial evidence that rimegipant can be an effective and well-tolerated alternative for menstrual-related migraine. However, no study had explored the prophylactic efficacy of rimegepant in pure menstrual migraine. To address this problem, we conducted a retrospective analysis to investigate the effectiveness and safety of rimegepant in the prophylactic treatment of pure menstrual migraine.