Safety and efficacy of hormonal therapies used to treat endometriosis in women suffering migraine

ABSTRACT Introduction Hormonal therapy is the cornerstone of long-term endometriosis management, especially for women deferring surgery. In patients with comorbid migraine – a common, disabling condition – therapeutic choices must balance efficacy with neurological and vascular safety. Areas covered This review summarizes hormonal therapies for endometriosis with a focus on safety in migraineurs. A comprehensive literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library up to March 2025. Expert opinion Combined hormonal contraceptives (CHCs) and progestins remain first-line options for treating endometriosis-related pain. CHCs are contraindicated in patients with migraine with aura because of the increased risk of ischemic stroke, while their prescription in migraine without aura should be individualized, considering also the fact that evidence in women with concomitant endometriosis is still limited. Progestins generally show better tolerability and may improve migraine outcomes, despite the occurrence of breakthrough bleeding or mood changes. Gonadotropin-releasing hormone (GnRH) agonists and antagonists are second-line options, providing effective pain control, although their effects on migraine are variable and headaches are a frequent adverse event. Add-back therapy is essential to mitigate hypoestrogenic sequelae, particularly about bone health. Overall, treatment should be individualized according to migraine subtype and vascular risk profile to ensure long-term safety, adherence, and therapeutic effectiveness. Article highlights Endometriosis and migraine frequently co-occur, likely due to shared hormonal and inflammatory pathways, complicating treatment strategies. Combined hormonal contraceptives (CHCs) are effective for endometriosis-related pain but pose vascular risks in migraine with aura, limiting their use in this population. Progestin-only therapies, such as desogestrel pills and the levonorgestrel intrauterine system (LNG-IUS), offer safer alternatives for women with migraine, with growing evidence supporting their dual benefit. Gonadotropin-releasing hormone (GnRH) agonists and antagonists are effective for refractory pain but may trigger headache-related side effects, requiring individualized dosing and monitoring. Inconsistent migraine effects occur with their use. Personalized treatment approaches are essential to balance efficacy and safety in women with both endometriosis and migraine, and future studies should target this underserved population. Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Reviewer disclosures Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Author contributions U Perrone: writing of the first draft. F Barra: writing of the first draft. G Evangelisti: literature analysis. A Izzotti: data analysis. C Gustavino: literature analysis. A Antonelli: supervision. U L R Maggiore: data analysis. Simone Ferrero: revising of the first draft, supervision. Data availability statement The authors confirm that the data supporting the findings of this study are available within the article.