Anti‐calcitonin gene‐related peptide treatments in women's health: Gaps and clinical evidence in menstrual‐related migraine, pregnancy, lactation, and hormonal contraception: A narrative review
Jelena Pejic, Jeya Anandakumar, Lisa A. Marks, Rashmi B. Halker Singh, Jessica AilaniAbstract
Objective
This study was conducted to review and synthesize current evidence on anti‐calcitonin gene‐related peptide (CGRP) therapies in women with menstrual‐related migraine, during pregnancy and lactation, and while using hormonal contraception.
Background
Migraine disproportionately affects women, with prevalence peaking during reproductive years when hormonal fluctuations modulate neurovascular and nociceptive pathways, including CGRP signaling, that contribute to migraine susceptibility. Despite the established efficacy of anti‐CGRP therapies—including monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and gepants (ubrogepant, rimegepant, atogepant, and zavegepant)—evidence regarding their use across critical reproductive health contexts remains limited.
Methods
A systematic search of MEDLINE and Embase was conducted using MeSH terms and keywords related to migraine, CGRP‐targeted therapies, and reproductive health contexts. Studies were screened independently by two reviewers. Data were extracted using standardized forms and synthesized narratively by clinical domain.
Results
Sixteen studies met inclusion criteria. For menstrual‐related migraine, post hoc analyses and observational studies demonstrate that CGRP monoclonal antibodies reduce migraine frequency both during and outside the perimenstrual window (galcanezumab: −5.1 vs. −3.2 days, p < 0.001), although the perimenstrual period remains a time of relatively higher headache burden despite treatment. Pregnancy data are limited to pharmacovigilance analyses and case reports of unintended exposures, which have not identified specific patterns of maternal, fetal, or neonatal toxicity. Phase 1 pharmacokinetic studies demonstrate minimal gepant transfer into breast milk (relative infant doses, 0.04%–0.19%), well below the 10% safety threshold, although no human lactation data exist for CGRP monoclonal antibodies. No studies specifically evaluated anti‐CGRP therapies in women using hormonal contraceptives.
Conclusion
Substantial evidence gaps exist across all reproductive health contexts examined. Prospective trials in menstrual‐related migraine, pregnancy registries, lactation studies assessing infant outcomes, and research examining interactions with hormonal contraceptives are needed to optimize migraine care for women.