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

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.